Translating Aging

In today’s episode, Chris is joined by Dr. Matthew "Oki" O'Connor, CEO for Scientific Affairs at Cyclarity Therapeutics, a company focused on eliminating arterial plaque, a prevalent issue in old age. Dr. O'Connor shares his insights on the causes and effects of atherosclerosis, the leading cause of death worldwide, and how aging contributes to plaque build-up. The podcast emphasizes the need for a paradigm shift in addressing cardiovascular disease and highlights the importance of new approaches to repair vessels throughout the body and brain.

Together, Chris and Dr. O’Connor begin by discussing atherosclerosis, its significant impact on cardiovascular disease, and the need to understand the molecular and biochemical mechanisms underlying aging and diseases related to aging. They also cover the limitations of current clinical treatments for atherosclerosis and the importance of a paradigm shift towards new approaches that can repair vessels throughout the body and brain. Dr. O’Connor then goes on to describe Cyclarity’s unique drug, a cyclodextrin, explaining how it could be a promising solution to the harmful effects of atherosclerosis. The podcast also explores the potential of combination therapy with traditional lipid-lowering drugs to address multiple aspects of atherosclerosis.

Join Chris and Dr. O’Connor here today to gain a greater understanding of the remarkable work undertaken by Cyclarity Therapeutics, the impact of aging on cardiovascular health, the need for new approaches to address atherosclerosis, and the unique drug therapy combination that may offer a promising solution, revolutionizing its treatment in the process.

The Finer Details:

• Cyclarity Therapeutics and the work they undertake 
• Atherosclerosis 
• Cardiovascular dysfunction
• The build-up of arterial plaque
• The implications of aging-related targets
• The need for a paradigm shift towards looking at new approaches to repair vessels 
• The limitations of current clinical treatments for atherosclerosis
• The limitations in the standard of care for LDL and HDL cholesterol
• Understanding the molecular and biochemical mechanisms underlying aging and the diseases of aging.
• The need for new treatments
• The cyclodextrin drug and how it works
• The need for combination therapies that will target multiple aspects of atherosclerosis
• Cyclarity Therapeutics’ trials

Quotes:

"Cardiovascular dysfunction, depending on which metastudy you believe, between 30 and 50% of all death on the planet is caused by the build-up of plaque in the arteries."

"Atherosclerosis is the thickening of the arteries, which means in the vessel wall, you have a build up of material called plaque, which starts out as a fatty streak in the wall of a blood vessel."

"There's no way to avoid the concept or the idea that a basic molecular mechanism, a biochemical mechanism of aging is going to impact many, if not all, cells and tissue systems."

"By the time that you're doing vascular surgery on somebody, you've kind of lost the game. You clearly missed an opportunity to prevent a bad thing from happening in the first place."

"We really need a paradigm shift to look at new approaches to addressing cardiovascular disease."

"I think the average non-specialist just thinks of cholesterol as this, like, weird molecule that's in your body for some reason, but is totally bad."

"Those lipid lowering drugs do actually save lives and keep atherosclerosis from getting worse faster. But we are trying to invent a better way to do it, a more elegant way to get rid of only the most toxic forms of cholesterol so that your arteries can repair themselves the way that they're engineered to."

"I imagine that our treatment, at least at first, will be paired with the standard of care, which mostly is currently lipid lowering treatments, at least at first."

"The things they're going after aren't just going to be treatments for a specific kind of cancer with a particular mutation or a very specific kind of skin disease. It's going to be something that affects many organ systems."

“Targeting aging is an effective way to prevent and treat atherosclerosis and cardiovascular disease.”

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Cyclarity Therapeutics

Dr. Marco Quarta, CEO and Co-founder of Rubedo Life Sciences, joins Chris on today’s episode to discuss his company’s strategy of targeting pathologic cells to develop therapeutics for chronic degenerative conditions. The conversation covers the evolving definition of senescence and the challenges of identifying and classifying pathologic cells, which vary across different tissues and indications. Marco also announces the upcoming Senotherapeutic Summit in November, which will bring together stakeholders from different fields to advance therapeutic research. 

Marco and Chris also review Rubedo Life Sciences' clinical development approach: targeting the aging process with the goal of helping healthy stem and immune cells to repair. They then go on to discuss the funding and work required for the selection and nomination of a lead candidate for a project, the importance of having access to primary clinical samples to test efficacy, and the subsequent steps of the grant awarding process. The conversation then turns to the value of having multiple programs running simultaneously. 

Tune in today to learn more about  the ‘sneaky’ process of senescence that accelerates aging, the toxicity of these rare cells and the development of small molecules that can target them, the complexities of developing new therapies, and the value of having a robust pipeline of programs to advance therapeutic R&D.

The Finer Details:

• Defining pathological cells and their role in chronic degenerative conditions
• Identifying, classifying, and targeting senescent cells
• The need for a focused effort in identifying specific targets for therapeutics
• The evolution of the definition of senescence and the existence of multiple types of senescent cells
• The Senotherapeutic Summit in November and its goal of advancing the field of therapeutics
• Running multiple programs simultaneously
• The upcoming event in Saudi Arabia aimed at accelerating and promoting healthy longevity.

Quotes:

"These are aberrant cells, dysfunctional cells, and maladaptive cells that are contributing to shift the microenvironment and leading to progression of chronic degenerative conditions, driving chronic inflammation, fibrosis, stem cell depletion, and cancer."

"There are no universal pathologic cells across all tissues or indications. So it really depends on your question and finding targets associated with those that you can really go after in a drug discovery pipeline to generate therapeutics." 

"We are hoping to push forward the conversation about what senescent cells are, how we can classify them, and how we can move forward with targeting these cells."

"We are testing back to back multiple indications including for example, chronic age related atopic dermatitis and others."

"And it's a very important event that we'll have major stakeholders from high level government officials and scientists and innovators business leaders and really the idea of promoting a healthy longevity and how can we accelerate this."

Links: 

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Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Rubedo Life Sciences

In today’s episode, Chris sits down with Kevin Caldwell, CEO, Co-Founder, and President of Ossium Health, a company that aims to improve human health and longevity through bioengineering - specifically using stem cell science to create materials for cell therapies. Together, they discuss Ossium’s approach: processing and banking of bone marrow from organ donors, which can then be cryopreserved and used for various clinical applications such as bone marrow transplants for blood cancer patients and emerging stem cell therapies. Kevin also shares details of his background as a lawyer in the stem cell industry and the potential of stem cell therapies in increasing the availability of bone marrow for treatment options.

He then goes on to describe his company's clinical programs and their goal of increasing the percentage of patients who ultimately get bone marrow transplants. In addition, he reviews the company's plans for using stem cell therapies in preventive medicine, their focus on improving long-term health and lowering costs, and the company's clinical trial for treating GVHD. Finally, he says a few words about Ossium’s place in the longevity biotech sector.

Listen in today to not only learn about the potential of stem cell therapies and the importance of increasing the availability of bone marrow for treatment options for blood cancer patients, but to also gain valuable insights into the future of healthcare itself.

The Finer Details of this Episode:

• Ossium Health and the work it does
• Processing and banking bone marrow from organ donors
• Kevin Caldwell’s professional background
• The potential of stem cell therapies and the impact of increasing the availability of bone marrow
• The clinical applications of cryopreserved bone marrow 
• The technicalities and the importance of cryopreservation of bone marrow.
• Ossium Health's clinical programs and their focus on treating patients with acute myeloid and acute lymphoid leukemia.
• The company's plans for using stem cell therapies in preventive medicine
• Their focus on improving long-term health and lowering costs.
• The goals of Ossium Health
• Ossium’s clinical trial for treating GVHD 
• Working with the FDA 

Quotes:

"Every year in the United States, there are about 20,000 people diagnosed with leukemia who go looking for a bone marrow transplant… 40% of those people… ultimately do not receive a transplant. Many of those people die while looking for a donor."

"Other people become so weak during the process of searching for a donor that they're taken off the list."

"There are also many emerging applications of the stem cells that are native to the bone marrow, treatments for diseases of inflammation, treatments that enable people to receive organ transplants without immunosuppression."

"Ossium has developed a process for processing and banking bone marrow from organ donors, cryopreserving those cells, and then doing further selection and engineering on the cells to prepare them for different clinical applications."

“There's a number of steps that we have to take to go from that solid bone to bone marrow for cryopreservation.”

"Our goal is to dramatically increase the percentage of patients who ultimately get bone marrow transplants."

"Bone marrow transplants are not FDA regulated. They're treated like organ transplants by law."

"One of the things about prevention that is most powerful is that if you achieve it, you can both improve long-term health relative to retrospective treatment, and ultimately lower cost. For us, prevention is a North Star.”

“If we think about our goal of trying to broadly improve human health, one system that is involved in our response to essentially all disease is the immune system.”

"At Ossium, what we're really building is the ability to systematically reconstitute, restart, reset, and renew the human immune system."

"For the rest of the recipient's life, they will produce blood and immune cells from the donor's bone marrow."

"One of the things that's exciting about that is that the donor cells will be able to recognize and respond to new disease threats."

“The set of innovations that is going to allow us to extend our healthspan meaningfully from what we have now toward something that gives us another chapter of healthy life is going to look very different from the set that allowed us to go from the lifespans we had a century ago to today.” 

Links: 

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Ossium Health

This week, we welcomes Peter Fedichev, an entrepreneur and scientist with over 20 years of experience in academic research and biotech business who has co-founded three biotech companies. He’s currently the co-founder & CEO of GERO, a longevity startup on a mission to hack aging. 

In this episode, Chris and Peter discuss GERO’s goal to accelerate our understanding of aging and create a therapy that will significantly extend a healthy human lifespan. First, they talk about the relationship between physics and biotech, and from there, the conversation moves to the importance of resilience in human and animal aging. Finally, Peter walks us through GERO’s drug discovery approach, how we can ‘hack’ complex dynamic systems and aging using AI, and shares his optimism about the future of aging research.

The Finer Details of This Episode: 

• Discussing complex systems and aging
• Understanding slower aging in some animals
• Resilience and dynamic stability
• The dynamic frailty indicator
• Models of premature aging and slow aging
• GERO’s drug discovery approach 

Quotes: 

“What we can do and what I think is very good to learn how to do in biology is to understand those universal properties that do not depend on fine details of life histories.”

“Obviously aging, that is a very slow process—so slow that almost everything averages out and people that are living under different conditions with totally different life histories are still living more or less the same long life.”

“It's easier to rejuvenate an animal which doesn't have any resilience because resilience means the ability to get back to the norm after the intervention. If you are resilient, either a bad effect like smoking or a good effect as your future aging drug will be small, and the more resilient you are, the smaller is the effect.”

“If you can only increase your lifespan once you're already unstable, the overall effect of such interventions from lifespan will be, unfortunately, incremental and limited.”

“It looks like our progress in chronic diseases is very slow. It's very slow because even though genome is cheaper, we have all genetic therapies, all kinds of new therapeutic modalities, everything, but for reasons that we need to understand, it's very hard to do drugs against chronic diseases in humans.”

“I think by bringing these ideas from neuroscience like your company is doing, like our company, like all our communities are doing, I think we will find ways to educate them. And who knows, maybe in five years, one of the major pharmas will start doing drugs against aging, using the techniques and the experience that we will help them to create; I think we're very close to this tipping point in the industry.”

Links: 

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Peter Fedichev on LinkedIn

GERO.AI

“Unsupervised learning of aging principles from longitudinal data” Avchaciov, K., Antoch, M.P., Andrianova, E.L. et al. Unsupervised learning of aging principles from longitudinal data. Nat Commun 13, 6529 (2022). https://doi.org/10.1038/s41467-022-34051-9

This week, Chris welcomes Morten Scheibye-Knudsen, Associate Professor at the University of Copenhagen, who’s on a mission to understand, modulate and treat aging and age-related diseases. His research group, The Scheibye-Knudsen Lab, is trying to understand the cellular and organismal consequences of DNA damage & repair with the aim of developing interventions for aging. Morten is also one of the chairs and chief organizers of the highly successful aging research and Drug Discovery conference, ARDD. 

In this episode, Chris and Morten talk about interventions in the aging process and why it’s important to better understand aging in order to hopefully treat age-related diseases someday. First off, they discuss the contribution of DNA repair pathways to aging, and then Morten explains the diverging consequences of DNA damage, establishing the pivotal role that DNA damage plays in the aging process. From there they delve into how ketones work in the brain, as well as the connection between the ketogenic diet and aging. Finally, Morten shares his experience with clinical trials, the Aging Research & Drug Discovery conference, and some exciting things to look forward to in the aging field.

The Finer Details of This Episode: 

• Discussing DNA damage and aging
• The importance of intervening in the aging process
• Clinical work and funding
• The connection between a ketogenic diet and aging
• ARDD 2022 Conference
• Exciting things in the aging field 

Quotes: 

“I think if we're interested in being able to treat diseases and treat chronic diseases, then we really need to understand the root cause of these diseases. And most chronic, non-communicable diseases are age-associated, and aging is the largest risk factor for these diseases. So something happens during aging that makes us susceptible to disease.”

“Your brain cannot metabolize fats very well, so it needs an additional food source when sugar is getting very low, and ketones are then a possible food source.”

“The ketogenic diet or ketosis had been used even in Roman times.  When someone had an epileptic seizure, people thought they were possessed by demons and then they put them in a cell and allowed the demons to burn themselves out. But in reality, they just left them in the cell until they went into ketosis. That's when the ketones probably broke the seizures.”

“I think that we still don't exactly know how good they are in terms of aging. But I think this is a really interesting research topic because it has been very difficult to separate the, for example, reduction in blood glucose effect from the increase in ketone effect. So these exogenous ketones will really be key to dissecting that relationship.”

“I think this is probably the most exciting part, I would say, of the aging field right now is the greatly expanding field of clinical trials actually targeting aging.”

“I can drive a small clinical trial, but to actually get products in the hands of people and drive change for regular people, we need companies, we need industry. ”

Links: 

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website bioagelabs.com

BIOAGE Labs Twitter @bioagelabs

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ARDD 2022 Website: https://agingpharma.org/ 

ARDD YouTube channel: https://www.youtube.com/channel/UClOnplI2mzpJlwdX3vlOMJA

Optimizing Healthspan through Longevity Medicine (Dr. Andrea Maier – The Center for Healthy Longevity)

Dr. Andrea Maier is an internal medicine specialist, geriatrician, and researcher whose work focuses on age-related disease, cellular senescence, and the translation of longevity science into clinical practice. Among her academic appointments are professorships at the Free University, Amsterdam and the Netherlands, the University of Melbourne in Australia, and the National University of Singapore, where she also serves as the co-director of the Center for Healthy Longevity.

On today’s episode, Dr. Maier joins host Chris Patil to discuss longevity medicine, her goals for building credibility in this emerging specialty, and how lifestyle changes are key to intervening in the aging process. First, she explains that longevity medicine means optimizing the state of health of an individual before a disease occurs by antagonizing the aging processes to be healthier for longer. This focus on delaying age-related disease differentiates longevity medicine from other specialties in its proactive attempt to prolong the healthspan rather than reacting after a disease has already occurred. Dr. Maier goes on to state her goals for this specialty, including educating laypeople and medical professionals, building a credible foundation and guidelines, and accelerating research in the field. She also suggests some promising areas of research, from diagnostic clocks to the credibility of supplements, as well as discussing lifestyle changes, an intervention already known to be effective against age-related disease. Dr. Maier then discusses her involvement with the first publicly funded outpatient clinic in longevity medicine, which she’ll be opening in Singapore in 2023, and the services it will provide. Finally, Dr. Maier closes the episode with her thoughts on democratizing longevity medicine and the future of the specialty, including her hope that, within ten years, we will see a shift toward preventing and lowering age-related diseases.

Episode Highlights:

• What is longevity medicine?
•  
• Building credibility in a new specialty
• The long-term impact of supplements and lifestyle changes
• Dr. Maier’s new outpatient clinic
• Democratizing longevity medicine

Quotes:

“What we would like to achieve is to optimize that function at that moment in time for that individual. And optimizing function means optimizing the cognitive function but also the physical function to prevent that age-related disease.”

“Nobody really knows or has really described what the effect is of these supplements over the life course and for whom. I think consumers need to know what the return on investment is of taking these kinds of supplements. On the other side, physicians should know what the possible return of investment is if these kinds of supplements are prescribed to healthy individuals if any.”

“We have already interventions in place, we have diagnostics in place. And that’s the reason why I, as an internal medicine specialist, I’m opening the first longevity clinic in a publicly funded hospital because I think it’s time, and I think it’s unethical to not apply this knowledge to the population and just wait until disease occurs.”

“Most importantly is that we have to give individuals the choice what they would like to achieve because if we want, as healthcare professionals, too much, and people will not stick to our recipes, nothing will happen. So it has to be a shared decision-making on what to do and what to leave out.”

“We should deliver care to everybody who needs our help. And I would say helping means, in my view, to prevent age-related diseases, and thereby reduce the cost to the entire society.”

Links:

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BIOAGE Labs Twitter @bioagelabs

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In today’s episode, Chris welcomes Sebastian Brunemeier, a biotech VC and company builder focused on longevity and regenerative medicine. Sebastien is the Co-Founder and General Partner of Healthspan Capital, a longevity VC firm that invests in biotechnology startups developing therapies to slow or reverse aging, and the CEO and Co-Founder of ImmuneAGE Pharma, a new company based on a drug discovery platform for immune rejuvenation.

At Healthspan Capital, Sebastian is looking to invest in fellow “true believers” in longevity and regenerative medicine—companies that understand the importance of aging as a focus for biotech and won’t pivot away from longevity as a focus.

 Sebastian’s newest venture, ImmuneAge Pharma, is focused on rejuvenating the immune system. With over 100 years of combined drug discovery expertise, the company aims to systematically identify small molecules that rejuvenate hematopoietic stem cells (HSCs). As Sebastian points out, the goal of longevity and regenerative medicine is not to extend lifespan at any cost, but rather to increase quality-adjusted life years.

The Finer Details of This Episode: 

• Healthspan Capital and the importance of aging as a focus for biotech
• Investing in fellow believers who won’t pivot away from aging
• Alzheimer's drug development and the “amyloid mafia”
• ImmuneAge Pharma and immune aging 
• The importance of restoring immune function
• Key misunderstandings of regenerative medicine

Quotes: 

“We noticed that there was a gap in the market for more traditional structured VC, the longevity biotech space, and actually I and my co-founders launched Healthspan because we were looking to invest our own money into a broadly diversified portfolio and a long bio space, and there was no way to do it. So we had to create it ourselves.”

“I would argue that if you have a drug that enhances robustness and resilience and extends lifespan, and it works in multiple different animal models and disease, contrived or not, that is a much stronger preclinical signal for efficacy down the road.”

“We've already found a couple of interesting molecules that we're doing med chem on to improve their properties that identify the molecular target. And so, we're hopeful that we'll find a whole pipeline of assets that rejuvenate the immune system.”

“If we can dramatically improve outcomes for patients who receive chemo, that would be an absolute home run. It's a huge unmet market need. And this is something that I would want for myself and my friends and family to be available.”

“We want to gently, slowly replace the existing HSCs in the niche.”

“I'm primarily not in this for the money at this point. I am in this to extend healthy lifespan in myself and my loved ones and the world, and showing Big Pharma that there is a new way, another world is possible. We can actually treat disease at the root cause: the fundamental biology of aging.”

“We want to compress the time in which we're spending years in poor health at the end of life, which is very expensive for the whole world and the whole system. ”

Links: 

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

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Healthspan Capital Website: https://www.healthspancapital.vc/ 

Sebastian A. Brunemeier on LinkedIn: https://www.linkedin.com/in/sebastianaguiar/ 

Longevity Marketcap Newsletter: https://sub.longevitymarketcap.com/ 

The DeSci movement: https://ethereum.org/en/desci/ 

Joining Chris on the podcast today is Nils Regge, Co-founder and Managing Director of Apollo Health Ventures.  As a social entrepreneur, company creator, and biotech expert, Nils built Apollo Health Ventures in 2016 to help health tech companies develop methods to prevent and reverse the aging process and extend the healthy human life span.  

At Apollo, Nils makes use of his dealmaking skills, business knowledge, and prior experience growing startups to help boost the success of biotech and health companies.  As the general public becomes increasingly interested in longevity and medical advancements continue to take place at rapid rates, Apollo is a leader in funding and fueling efforts to ensure  healthier  and longer human lifespans. At the moment,  things are looking up as there is a lot of excitement  in the industry - however, Regge finds it important to temper that enthusiasm with the right kind of skepticism.   In a field in which any new advancement is seemingly revolutionary, it’s crucial to stay grounded. 

The Finer Details of This Episode: 

• Incentive and organizational structures
• Filtering for good ideas
• Apollo’s portfolio of companies 
• Fusing European and American techniques for company building
• The heightened need for funding
• Bringing drugs into the clinic

Quotes: 

“If you have something that makes you live 10 years, 20 years, longer, healthier, I think it's the biggest market ever.”

“We do company creation, but we also invest in outside companies.”

“Because we are in this for the long run, we want to make investors money, we want to show the investors that this is a good place to invest or a good space to invest. And then ultimately, we want to be able to raise more money from other bigger institutional investors.”

“You want to create an incentive structure and organizational structure that encourages the right kind of skepticism…you almost want to avoid a certain kind of optimism early on.”

“But because of the excitement in the field, and kind of what I think of as the ‘True Believer' phenomenon, I think we are vulnerable to a little bit of hype. And I think that it's a very good idea to bring that down to earth and say, ‘Okay, that's a good idea. Let us figure out the best way to see if it's gonna fail, and do that first.’”

“So first of all, it's about getting a drug to the market, that's the most important thing, and making sure it's safe and that it's working.”

“There's great science here in Europe, right? So I mean, the universities are great, the people are smart. They're just not as entrepreneurial as they are in the US, per se.”

Links: 

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Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

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Apollo Health Ventures Homepage: https://www.apollo.vc 

Nils Regge on LinkedIn: nils-regge-62ab7a28 

In this episode of the BioAge podcast, Ann Beliën joins Chris Patil today to share the story behind Rejuvenate Biomed, and her journey into the longevity sector.  She started her career at Johnson & Johnson after receiving her postdoctoral degree, and during her tenure, she worked in scientific, operational, and strategic roles.  Twenty years later, she became the founder and CEO of Rejuvenate Biomed, a Belgian company evaluating combinations of safe and synergistic drugs that target physical decline and promote healthy aging.

One of Rejuvenate’s main focus areas is sarcopenia, the loss of muscle mass and strength during aging. When muscle decay starts to prevent people from leaving the house and living a quality life, mental health and quality of life decline rapidly.  The company’s first combination therapy to reach clinical trials, currently in a Phase 1b study, will be initially tested as a treatment for this complex disease.  More clinical trials are in the works, with two new combinations entering preclinical trials next year.

The Finer Details of This Episode: 

• Longevity sector outside the U.S.
• Working for Johnson and Johnson
• Rejuvenate BioMed’s in silico analysis 
• The complexity of sarcopenia as a disease
• Phase 2 clinical trials
• The funding environment

Quotes: 

““If we want to do something in the longevity space, we need to provide the product in a chronic fashion, and safety is of course very important. So, why not start from something that already has a proven safety record?”

“The company is first identifying individual drugs that have interesting properties with respect to aging, and then trying to devise novel combinations of them that can be used to treat age related diseases.”

“Aging is not currently an endpoint that can be used as a trial outcome. So to bring drugs to trial, we have to identify appropriate clinical indications.”

“People with sarcopenia are not able anymore to go to the store, to leave their house.  And the social impact is huge… they become isolated.”

“We want to have functional, happy people that are living their lives to their fullest potential for convenience.”

“We want to learn as much as possible also from the technical perspective, which can be an added benefit not only to the company, but also to the community on the comparisons of these different methods of measuring muscle mass.”

“I think we've also seen that in the United States, where the biggest science story of all of our lifetimes, the COVID pandemic, revealed the importance of thinking hard about diseases that disproportionately affect older people, and the broader ramifications of that for the rest of the population.”

“Your advisors should be representing different aspects, different ways of thinking and different challenges. So our advisory boards are always very interesting, because you get all these different perspectives.”

“In the aging field, people always dive deep and figure out the positive side and do the learning and just pull it through. And that's what I really like.”

Links:

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BIOAGE Labs Website BIOAGELabs.com

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Rejuvenate Biomed Homepage: rejuvenatebiomed.com

Today’s guest on the podcast is Marc Bernegger, a serial tech entrepreneur who has been following developments in the field of longevity since 2009. Recently he became a founding partner of the Swiss company, Maximon, whose core missions is building companies and providing support to longevity entrepreneurs.

Marc has worked for over a decade between two continents at this point, and his interest in longevity has never been more intense.  From aging skin to gut microbiomes, there’s a lot of work and research left to do, and if you’re of Bernegger’s school of thought, longevity is a matter of the present, rather than some notion about the distant future.  As you will hear today, Marc is like so many others in his field -  putting in the work now to create a better tomorrow.  

The Finer Details of This Episode:

• Entrepreneurial support
• Maintaining a growing company
• The future of aging skin
• Cooperation in the longevity biotech sector
• Investment attitudes in the US and Europe
• Seeing longevity as a present issue

Quotes: 

“Our ambition is to only focus on businesses where there's a real scientific background, so not selling snake oil, which is maybe on the short term very profitable but definitely not sustainable.”

“We support them from day one. We help them with all our network experiences and learnings as serial entrepreneurs ourselves. We support them with money. And we really try to be a sparring partner without maybe becoming too annoying.”

“​​I think for me as an entrepreneur, that's always very fulfilling that you can give, be an alternative, and create more entrepreneurs starting companies.”

“One of the reasons we decided to launch Maximon as a company builder is that we wanted to show that it’s possible to monetize the megatrend of longevity as we speak.”

“You can really boost and accelerate the growth by combining some of the different business models.”

“By having more elderly, healthy, longer living people, a lot of business models will change. So elderly living is a big topic. Something we're looking into is the whole gut microbiome, but also microbiome in other areas where you have a huge impact on longevity.”

“The longevity biotech sector, even in the regulated drugs space, is pretty cooperative. We don't think of ourselves as competitors, because everyone wants everyone else to succeed.”

Links: 

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Maximon Homepage

Joining Chris today is Dr. Vadim Gladyshev, Professor of Medicine at Harvard Medical School, Director of Redox Medicine at Brigham and Women's Hospital, and a member of the National Academy of Sciences. The Gladyshev lab studies redox biology and trace elements as they relate to cancer, reproduction, and aging. Today, Dr. Gladyshev shares with us how his research group investigates the aging process and how aging is quantified in academic research.

Dr. Gladyshev begins by discussing how he got involved in the longevity sector. He goes on to explain that aging has not been clearly defined, and how many researchers define aging differently. He contends that aging should be studied as opposed to age-related diseases because age-related diseases are influenced by other factors aside from aging. The interview concludes with the importance of conferences that address the science of longevity and how these events connect bright minds to tackle unsolved problems in the field.

Episode Highlights:

• How Dr. Gladyshev got involved in aging
• The relationship between selenium and longevity
• How longevity is studied in the Gladyshev lab
• What is rejuvenation?
• The importance of measuring the aging process using clocks
• Using experimental and computational methods to alter clocks
• How the biotech industry quantifies aging
• Targeting aging and not age-related diseases
• The importance of conferences targeting longevity

Quotes:

“In general we try to address fundamental questions in the biology of aging — really trying to understand, ‘What is aging? How can we fundamentally adjust lifespan or target aging?’ … And we try to identify new areas of potential growth for the field.”

“We work on cross-species analysis to understand how the lifespan is shaped over evolutionary timescales and how we can utilize what we learn from evolution in targeting aging and lifespan.”

“Many changes can be measured as an organism moves from young to old. So this might be useful for measuring the progress of normal aging. But when you're intervening in aging, you don't want to reverse all of those changes, because some of those changes are evidence of the body's protective responses in action.”

“Just to play devil's advocate for a second: why would you want to target aging if you still got sick and died at the same rate?”

“Mortality is an integrative feature of not just the aging process, but interaction with the environment.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dr. Vadim’s Linkedin

Gladyshev lab Website

Gladyshev lab Twitter

Joining Chris today is Alex Zhavoronkov, CEO and Co-founder of Insilico Medicine, an artificial intelligence–driven pharma-technology company with a mission to accelerate drug discovery and development. Alex is a lifelong advocate for longevity biotech and the author of The Ageless Generation: How Advances in Biomedicine Will Transform the Global Economy. Today, Alex shares the accomplishments that Insilico Medicine has achieved in drug discovery and how AI and robotics come into play.

The episode begins with Alex narrating his experience in the field of longevity and how his interest developed at a young age. He discusses the reason behind building Insilico Medicine, how AI and robotics aid drug discovery in the longevity industry, and how biology and chemistry play a significant role at Insilico Medicine. The episode ends with Alex describing the future he sees for Insilico Medicine and how they can improve human life using AI to advance drug discovery and data generation.

Episode Highlights:

• What fueled Alex’s interest in longevity
• Building Insilico Medicine
• How tech is used at Insilico Medicine
• The role of AI and robotic systems
• How AI and robotic systems can improve the longevity space
• The future of Insilico Medicine

Quotes:

“It always fascinated me how we grow, mature, reach our peak, and then decline and die. At the end of the day, it doesn't matter what you do, you lose everything… So, the rest of my life is dedicated to aging research.”

“We started generating novel molecular structures with the desired properties, and managed to achieve spectacular results.”

“In human clinical trials, we realized that we can use some incremental data that could be generated using a robotic system. So now we're building one of the most advanced labs in the world focused on data generation, and also personalized medicine that can take in specific biological samples.”

“BioAge is one of the leaders in the space, showcasing that it can identify targets using longitudinal data that is available from biobanks.”

“We trained neural networks to predict age first, and then retrain them on diseases or on other conditions, that is, any data type that is changing in time.”

“By training on age, you are training on the most important feature that connects all of us.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Insilico Medicine

Back in the host's chair this week, Bob Hughes welcomes Dr. Bill Evans, one of the world's foremost experts on muscle aging, to the podcast. Bill is adjunct professor of Human Nutrition at University of California Berkeley and an adjunct professor of medicine in the Geriatrics Program at Duke. Previously, he was vice president and head of Muscle Metabolism Discovery Performance Unit at GlaxoSmithKline and he was also president of the Muscle and Health Division at KineMed. He was also president of the Muscle and Health Division at KineMed. Earlier this year, he was recognized with a Lifetime Achievement Award at the 2022 International Conference on Frailty, and Sarcopenia Research. Today, Bill brings his vast amount of experience and expertise to the podcast to discuss how muscle aging affects longevity in older people and the relationship between muscle aging and age-related diseases.

He begins by sharing his experience in the longevity industry, particularly with muscle aging, and goes on to discuss the term ‘sarcopenia’, including what it means and how it relates to muscle degeneration. He then explains the differences between sarcopenia and cachexia, and referring to several studies, shares the meaning of frailty, the relation of walking speed with age, and the importance of the brain–muscle connection. At the conclusion of the episode, Bill discusses the future of muscle aging and how the longevity industry hopes to find solutions that will improve the lives of people on a global scale.

Episode Highlights:

• Bill’s journey in the muscle aging industry
• Why muscle degeneration?
• The origin of the term ‘sarcopenia’
• The differences between sarcopenia and cachexia
• Is sarcopenia due to dysregulation of neuronal inputs?
• The contribution of fast-twitch and slow-twitch muscle fibers in aging
• Sarcopenia and age-related diseases
• What is frailty?
• Why our walking speed slows down as we age
• The relation between exercise and psychological state
• The brain-muscle connection
• The future of the longevity industry from Bill’s viewpoint

Quotes:

“What are some of the causes of late life disability? How does muscle change as we grow older? Why do we lose muscle?”

“A large percentage of women in particular over the age of 60 reported that they couldn't even lift 10 pounds. And the muscle weakness progressed as they grew older.”

“The primary deficit and functional deficit as we grow older is loss of strength. And that is directly related to how much muscle we have.”

“Cachexia is associated with a rapid increase in the breakdown of muscle, while sarcopenia is associated with a more gradual decrease in the rate of synthesis of muscle.”

“People generally over the age of 75, have circulating markers of inflammation.”

“People with type two diabetes and insulin resistance lose muscle at almost double the rate of people with normal glucose tolerance.”

“If we improve strength in an older person, their spontaneous activity goes up. And their habitual walking speed goes up as well.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dr. Bill Evans on LinkedIn

This week’s episode of Translating Aging features Robin Mansukhani, CEO and Co-founder of Deciduous Therapeutics, a company that aims to positively impact human healthspan by developing medicines which activate the endogenous immune mechanism responsible for the elimination of senescent cells. Today, Robin shares his insights on how senescent cells develop and how Deciduous Therapeutics eliminates them.

Robin begins by explaining what causes the growth of senescent cells. He explains that not all senescent cells are dangerous and discusses the various kinds of these cells. Although senescent cells are prominent in age-related diseases, Robin explains that they are also found in younger people with autoimmune diseases such as juvenile diabetes. He goes on to talk about Deciduous Therapeutics’ approach in combating senescent cells by activating the NKT cells. He also shares his thinking about the best directions for human trials. The episode concludes with Robin describing the future of Deciduous Therapeutics, and his focus on impacting people globally in a meaningful way.

In this episode, you’ll learn how senescence arises, traditional senolytic approaches, and the importance of NKT cells in eliminating these pathogenic celss.

Episode Highlights:

• The origin of senescent cells
• Why are senescent cells highly pathogenic?
• Breaking down the different kinds of senescent cells
• The relationship between senescent cells and age-related diseases
• Senolytics and senostatics: approaches for getting rid of senescent cells
• Deciduous Therapeutics’ approach
• What happens when senescent cells overpower NKT cells?
• The role alpha-galactosyl ceramide on NKT cells
• The current hurdles Deciduous Therapeutics are trying to overcome
• How Robin see Deciduous Therapeutics in five years

Quotes:

“Senescent cells are cells that have been irreversibly damaged, and so they exit the cell cycle.”

“It's not about the age of the person. It's more about the biological age of the organ and tissue. So we see senescence, also, in young people.”

“If you can take a senescent cell that's pathogenic and make it good again, and make it functional again safely and successfully, that would be very useful.”

“The approach here and our mindset going into creating this company was: there's a way that nature intended for this to happen, and it is our job to figure that out.”

“Getting the first indication to work means that you'll have a runway to lots of success. But if your first one does not work, in a lot of cases, it might mean the end of the company or the end of the runway because you simply don't get enough funding for multiple clinical trials at once. So it is critical.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Deciduous Therapeutics Website DeciduousTx.com

In today’s episode of Translating Aging, Chris welcomes Mark Hamalainen, the founder and director of LessDeath, to discuss how to encourage the influx of talents into the longevity field. LessDeath is an organization on a mission to support the growth and effectiveness of the longevity industry’s workforce. Today, Mark shares with us his experience in the longevity space, why he founded LessDeath, and what to expect at the upcoming LessDeath Longevity Summer Camp.

Noting that his experience in the longevity space was propelled by his fascination as a teenager, Mark goes on to share details about leaving his Ph.D. program to get hands-on experience in the longevity world and discover the many talents represented in the industry. He speaks about founding LessDeath, what the organization hopes to achieve, the inaugural LessDeath Longevity Summer Camp and the gap this event is hoping to bridge in the industry. Included in this episode are interviews with Stephanie Dainow and Kia Winslow, camp counselors for the Longevity Summer Camp, in which they share the kinds of talent they expect to attract to the event and the kinds of activities that will take place.

Episode Highlights:

• How Mark got involved in the longevity space
• The biggest issue in the longevity field
• The different talents prospering in the biotech field
• Why gene delivery and gene therapy require more technological development
• The challenges with getting people into the longevity biotech field
• How LessDeath tackles the talent issue and encourages networking
• The LessDeath Longevity Summer Camp
• Interview with Stephanie Dainow
• How Stephanie got into the longevity space
• Interview with Kia Winslow
• Kia’s story of getting into biotech
• What is next for LessDeath?

Quotes:

“I started a Ph.D. at Cambridge working on some gene therapy development. But I quickly got a bit disillusioned with the pace and the amount of extra work involved in grant writing, bureaucracy, and academia.”

“A lot of people would prefer to work on important problems like longevity, climate change, building a multiplanetary species. But it can be difficult to know where to start, and how to build a sustainable career out of it.”

“I've never liked the idea of getting older and losing my faculties and physical capabilities.”

“If you want to invest your time supporting initiatives that drive measurable improvement to the human condition, but you're really not sure where to start, this is the event for you.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

LessDeath Website LessDeath.Org

Apply for LessDeath Longevity Summer Camp

Mark’s LinkedIn

On today’s episode of Translating Aging, Chris welcomes Tyler Golato and Laurence Ion to talk about VitaDAO, a collective accelerating research in human longevity and decentralized drug development.  The pair start the conversation off by discussing their company’s roots -  a previous business venture that sought to change the incentive structures around drug development.  VitaDAO was created as a means to support biological longevity research through decentralized means.  

They go on to discuss VitaDAO’s future, how they can increase liquidity, and their goals to advance drug development.  Golato and Ion argue that the present is a perfect time to create VitaDAO, given the current intersection between biotech, block chain, and longevity research.  They conclude by recalling the early-life dreams that inspired them to enter this field. 

Episode Highlights:

• The essence of VitaDAO
• Changing the incentive structures around drug development
• The partners’ passion for longevity
• VitaDAO’s decentralized structure 
• Project sourcing and funding
• Increasing liquidity
• Goals to end drug development
• The intersection of biotech, block chain, and longevity
• Why Tyler and Laurence are interested in longevity

Quotes: 

“VitaDAO was born out of an early concept that we had been working on at a company called Molecule, which is a company that I co-founded about three years ago with a vision of doing decentralized drug development.”

“It's not completely open, completely decentralized to the point where it's paralyzing for the organization, but we try to look at the things that are most valuable to decentralize in order to make the organization as maximally efficient as possible.”

“We really try to make it as easy as possible for token holders to make informed decisions about whether or not something is ultimately worth funding. We like to do so once we're at the point where we ensure that we can actually progress with a deal.”

“We are distinctly different from a venture fund in terms of our endpoint is not really ROI impact, it's really impact in the space. And that comes in many different forms, in terms of taking a diversified approach to funding longevity research.”

“Even if we spin out a NewCo, these contributors can vote on what projects are funded, how they are spun out, and then they can co-invest and help these therapeutics eventually come to market.”

“In the long term, we really hope to be able to do a lot of things within the decentralized science ecosystem as the space broadens and has liquidity to do so through partnerships with organizations like Molecule and LabDAO.”

“Certain things like clinical trials don't yet have a business model. So we can create one by having either philanthropic groups, patient groups or even a government/life insurance company that has an economic incentive to improve health outcomes.”

“Crypto has long been dismissed by the incumbents.”

“People who are really looking at how technology and innovation can drive humanity forward and drive the way that we govern.”

“What problem is more interesting than human aging? I mean, for me, it's so philosophical; it's so poetic.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

VitaDAO Homepage

On today’s episode of Translating Aging, Chris welcomes Nathan Cheng, the program director at On Deck Longevity Biotech (ODLB), to discuss how ODLB is cultivating new founders and connecting people in the longevity biotech space. Nathan writes about the longevity biotech industry in his Longevity Marketcap Newsletter, is the founder of Longevity List which aims to connect job seekers, companies and investors in the longevity industry, and is on a self-professed mission to end biological aging, Today, he tells us about the purpose of ODLB, its achievements thus far, and the bridge it hopes to build in the longevity biotech industry.

Nathan begins the conversation by discussing what On Deck is and why the company was formed. He briefly narrates his journey in tech, what increased his interest in the longevity space, and the mission of the ODLB, as well as how the fellowship works towards creating founders. He goes on to discuss the obstacles many face when they get accepted in the fellowship and how ODLB works to reduce those obstacles by promoting face-to-face interactions. Also contained in this episode are brief interviews with ODLB fellows Brian Hodge and Gabe Warshauer-Baker.

Episode Highlights:

• What is On Deck?
• Nathan’s journey in the longevity space
• On Deck Longevity Biotech’s (ODLB) mission
• The importance of connecting those in the longevity biotech space
• How mentors contribute in ODLB
• Does the startup culture reward extroverts over introverts?
• Getting into the ODLB fellowship
• Interviews with ODLB fellows
• Feats the ODLB has achieved
• The future of the longevity biotech space

Quotes:

“At a high level, On Deck is where people come to start and accelerate their companies. It's also a place where people start and accelerate their careers in the startup economy.”

“What makes On Deck unique is that it's a huge network of interconnected program communities. So we have communities centered around specific career goals.”

“ODLB’s mission is to increase the number of people working to build longevity biotech startups.”

“For some people coming from the scientific domain, this whole idea of networking is foreign to them or nebulous.”

“We're gonna generate new founders, but among the people who decide for whatever reason not to become founders, we also want them to be encouraged and empowered to be involved in longevity biotech in some other capacity.”

“Putting ourselves on the map for people who are interested in building longevity biotech, I think that is our greatest achievement so far. ”

“So I think just more efforts in popularizing this geroscience paradigm, you know, actually targeting aging, I think there's a lot to be done there as well.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

On Deck Longevity Biotech Website

Nathan Cheng Twitter

In today's episode, Chris is joined by two leaders of the Alliance for Longevity Initiatives, A4LI, the first and only 501(c)(4) nonprofit organization founded with the goal of creating social and political action around the issues of combating age-related chronic conditions and increasing our number of healthy, disease-free years.  Sonia Arrison is a best-selling author, analyst, entrepreneur, and investor who is founder of 100 Plus Capital, Chair of the Alliance for Longevity Initiatives, co-founder of Unsugarcoat Media (acquired by Medium), and an associate founder of Singularity University. Dylan Livingston, the founder and president of A4LI, has a background in political organizing at the state and national levels.

The conversation begins with our guests reviewing their journey to the world of longevity science and ultimately A4LI. They then explore many aspects of their organization including the needs it will address, the obstacles it will encounter and how it will overcome them, and its plan for succeeding in its mission. They go on to share what they have already accomplished, their ties on both sides of the aisle in Congress, Silicon Valley's current perspective on their work, and how listeners can help them achieve their mission. Drawing the episode to a close, Sonia and Dylan share their vision for what success would look like for A4LI five years down the road.

In this episode, you will learn about the need for an organization such as A4LI to create social and political action around age-related conditions, and how our guests plan to fill this need both  now and into the future.

Episode Highlights:

• Sonia and Dylan's journey to the area of longevity and longevity science
• How they both came to be involved with A4LI
• The unmet needs that A4LI will address
• The obstacles it will meet in pursuing its mission and how it will overcome them
• The sense in which biology of aging is underfunded
• A4LI's plan for succeeding in its mission
• The Regenerative Medicine Advanced Therapy designation
• What it has accomplished already
• The ties it has made with both Democrats and Republicans
•  
• Silicon Valley's perspective on their work
• How researchers, entrepreneurs, and investors can help A4LI
• Sonia and Dylan's vision of success for A4LI in 5 years
• 
  

Quotes:

“Sonia has been intimately involved since the organization's inception. And I'm really happy that she is able to be the chair of the board because her leadership and guidance has been absolutely crucial.”

“Essentially A4LI will be establishing a line of communication between the longevity industry and elected officials.”

“There's a lot of longevity companies out there who are doing some really cool things that are going to extend our health spans. And, and so we need to make sure that the atmosphere is right for that.”

“We look to kind of educate, you know, not only politicians, but also the voting public on what's possible.”

“What we're saying here is, what I hear you saying is, it should be okay for a company to say we're a longevity company.”

“You'd think that the government would want to fund that more, and they should, because of the e massive impact that a drug that treats aging could have.”

“Even if funding is coming in from the private sector, biotech companies still stand to gain from formalized efforts, because they're going to get a smoother regulatory environment and potentially greater legitimacy for the products and ideas that they're developing. “

“By simply doing what other advocacy efforts do - that is public persuasion campaigns, their advertising - I think we can really open some ears up and get people focused on this space a little more.”

“One of the things that was really important to me about getting involved in this is that it remained bipartisan, and so far, we've managed to do a really good job of having people on both sides of the aisle.”

“I think people in Silicon Valley are interested and excited, and are just sort of waiting to see what's going to happen, and, you know, just how interested Congress might be.”

“Everything is going to change with the introduction of an effective longevity drug. So, you know, we need to help the government and institutions prepare for that.”

“Once somebody starts stealing your idea, you know that it's gold.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

A4LI Homepage

Today’s guest is Dr. Morgan Levine, an assistant professor of Pathology and Epidemiology at Yale School of Medicine. She is also a Founding Principal Investigator at Altos, a new biotechnology company focused on cellular rejuvenation programming to restore cell health and resilience. Dr. Levine shares her expertise on biological aging, aging clocks, cellular reprogramming, and a peek into the research she’s currently undertaking at Altos here today.

She starts the conversation by explaining the differences between biological aging and chronological aging. She then delves into topics surrounding biological clocks such as DNA methylation, and discusses her work at Altos and how this will differ from an academic environment.  Dr. Levine finishes up by highlighting what Altos hopes to bring to science and biotech in years to come.

In today’s episode, you’ll learn the difference between biological and chronological aging, the nature of biological clocks, and some of the exciting work taking place in biotechnology these days.

Episode Highlights:

• The difference between chronological aging and biological aging
• What is an epigenome?
• How DNA methylation is measured
• Using aging clocks for a particular demographics
• How to decide if a discovery slows the biological clock
• Applications of clocks as it pertains to aging and longevity
• The costs of individual measurements
• Dr. Morgan’s work at Altos
• How Altos was founded
• Deciding the direction of research
• Understanding cellular reprogramming
• The future at Altos

Quotes:

“Age measured in chronological time was the biggest risk factor for most diseases.”

“I like to think of the epigenome as almost the operating system of a cell.”

“The things that we assume should affect aging, in potentially an animal model, show effects when using the epigenetic clock.”

“We've actually taken the human epigenetic clock and broken them out into.. what we would call different modules.” 

“If we're measuring biological age, it should first correlate with chronological age to some degree, but not perfectly.”

“We’ve become much more interested in understanding the clocks rather than developing new clocks… What’s driving the changes that are captured by the clocks, and how do those link to the outcomes they’re associated with?”

“My lab is really a combination of both experimental wet lab people and computational dry lab people.”

“I think  saying we just work on aging, or just work on longevity, is really constraining us to some degree.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dr. Morgan’s LinkedIn

Altos Labs Website

Today’s guest is Dr. Thomas Rando, Professor, Neurology; Molecular, Cell and Developmental Biology, and a pioneer in stem cell biology and the biology of aging. Dr. Rando is the Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles, and the co-founder and Chair of the Board of Directors at Fountain Therapeutics. In today’s episode, he shares information surrounding cell cycle, parabiosis, and replacement therapy.

Dr. Rando begins by explaining why the cell cycle is important and the place of aging cells in the world of cell cycle. He explains the quiescent states of cells and how heterochronic parabiosis has been tested on animals to determine if cells in a younger animal can be used to activate those in an older animal. He also discusses how three factors impact aging: genetics, diet, and exercise.

In this episode, you’ll learn the meaning and importance of cell cycle and parabiosis and how they both relate to aging.

Episode Highlights:

• Dr. Rando’s transition from neurology to stem cell biology
• The importance of cell cycle
• Why aging cells do not repair tissues
• Exploring the quiescent state
• How heterochronic parabiosis works
• Chronic inflammation in older people
• Does exercise benefit the tissues in the body?
• The connection between exercise and replacement therapy
• The relation between diet and longevity
• What are ketogenic diets?
• Dr. Rando’s thoughts on supplementation
• The future of stem cell therapy
• Can bone marrow be used to rejuvenate older people?
• Can stem cell therapy treat Alzheimer's disease?
• Transitioning from an academic to a founder
• 
  

Quotes:

“Why is it that we heal our injuries and wounds less well as we age?”

“The older we get, the more difficult it is to activate these cells out of that state. And you can imagine that if a cell is dormant, and you can't wake it up, it's not going to do very well in terms of repairing tissues.”

“There's no free lunch here. What benefits the old animal hurts the young animal.”

“The only reason why a species survives and thrives and continues is because of reproduction.”

“No one wants to calorically restrict for their whole life. I mean, no one wants to go through their life eating 30%.”

“Anything that we can do to find a healthy diet that is palatable and sustainable, and prevents obesity will be a good thing.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Fountain Therapeutics

Dr. Marco Demaria is an Associate Professor in Cellular Ageing at the Medical Faculty of the University of Groningen. In 2018, he co-founded a start-up company, Cleara Biotech, devoted to developing anti-senescence drugs. Today, Dr. Demaria shares his insights and research on how senescence promotes aging and factors that promote the creation of senescent cells.

In this episode, Dr. Demaria explains what cellular senescence means and discusses the good and bad that comes with having senescent cells in the body. He explains the role of senolytics in combating senescent cells and how senescent cells could be the cause of the severity of COVID in older people.

In this episode, you’ll learn how senescent cells contribute to aging, the evolution of the senescent field, some current studies in the field, and what Dr. Demaria hopes to see in the field in years to come.

Episode Highlights:

• What is cellular senescence?
• The positive and negative sides of senescent cells
• The role of senescent cells in aging
• What is the heterogeneity of senescence?
• Using senolytic drugs to eliminate senescent cells
• How does hypoxia affect senescent cells?
• The relation between senescence and COVID in the elderly
• Dr. Demaria’s progress in his study and work at Cleara Biotech
• The evolution of the senescence field in the past 12 years
• Experiments Dr. Demaria would like to see done

Quotes:

“A cell that is in an early senescence state seems to be different from a senescence cell in a late state.”

“The next generation of senolytic drugs should definitely focus on dissecting the targets that they want to reach, because of the potential side effect of administering a general senolytic that could interfere with beneficial senescence.”

“What we call senolytic drugs and compounds are mostly repurposed drugs.”

“We also want to make this study of stem cell longevity in mice and in mouse tissues, because we think that might be another mechanism by which we can improve health, which is maintaining the stem cell pool because we retard the aging of the stem cells.”

“There are two prominent senescence groups that are now using senolytics in the clinic for COVID-19 patients.”

“There is no magic bullet so far that we have found but just because we haven't probably combined the right interventions at the right moment in the right context.”

“The experiments I would like to see done are to combine approaches that target different aspects of aging.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Cleara Biotech Website

The TAME trial and beyond (Dr. Nir Barzilai)

Dr. Nir Barzilai is the founding director of the Institute for Aging Research, the Nathan Shock Center of Excellence in the Basic Biology of Aging, and the Paul F. Glenn Center for the Biology of Human Aging Research at Albert Einstein College of Medicine of Yeshiva University. He is also the author of the book Age Later. Today, Dr. Nir brings his expertise to the podcast for a discussion regarding longevity and aging.

Nir starts the conversation with a discussion on the existing regulatory frameworks that create impediments to the longevity biotech sector such as the FDA regulations. He also explores the use of metformin in combating age-related diseases, the clinical trials surrounding metformin being carried out in the Longevity Biotech Association, dealing with members of  the government, and his perspective regarding what longevity biotech will be like in 5 years.

In this episode, you’ll learn the uses of metformin and its relation to age-related diseases and what Nir hopes to see in the longevity industry in years to come .

Episode Highlights:

• The existing regulatory frameworks that create impediments to the longevity biotech sector
• What is metformin and its relationship with age-related disease?
• Targeting aging with metformin — the TAME trial
• How other biomarkers would be tracked in the study
• The future of the trials and what is set to happen after it ends
• Examining the economics
• The mission of the Longevity Biotech Association
• The longevity industry in 5 years
• Challenges that come with conversing with the Government concerning longevity and aging

Quotes:

“Aging drives diseases and those diseases can be delayed.”

“If aging drives all diseases, then it's the mother of diseases.”

“After all, what are we trying to do? We are trying to prevent a cluster of age related diseases.”

“Even if metformin doubles in price because of demand, it's still going to be the cheapest drug in the pharmacy.”

“There are nine studies that show that people on metformin had less hospitalization, and less mortality from COVID if they were on metformin.”

“Science is not a bipartisan issue.”

“We need to extend the field and extend the actual funding to do it.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dr. Nir Barzilai’s Twitter

Professor Steven Austad is a distinguished researcher in geroscience and the Protective Life Endowed Chair in Healthy Aging at the University of Alabama at Birmingham. He's also the Director of the Nathan Shock Center at UAB and the Senior Scientific Director of the American Federation for Aging Research.

Today, Professor Austad joins Bob Hughes to discuss the biology of aging. He begins by narrating the discovery that sparked his interest in aging and his transition from animal behavior to the biology of aging. He discusses how these discoveries led him to the rate of living theory—the idea that the rate of aging is determined by your metabolic rate—and explains a somewhat paradoxical aspect to this theory: the hummingbird, which has a high metabolic rate, is  relatively long-lived. He goes on to review evolutionary ideas to understand the rate of living theory, shares his striking discovery about how possums age more slowly in the absence of predation, and describes both why birds of flight live longer than terrestrial birds and the unusually long lifespan of bats.

Professor Austad talks of how natural history observations can accelerate more molecular and pharmacologic insights into human health, explaining, “Evolution is smarter than you.” He shares his perspective of the research enterprise: what we do well, what we don't do well, and how we can be better. He also details where he stands on aging in the private sector and for-profit aging companies, the mechanisms of age-related decline, and gives details about his bet with Jay Olshansky about a 150-year-old person being alive by 2150. Finally, Professor Austad reveals his expectations on whether more people will live to be more than 120 or 150 in the second half of the century due to interventions, and shares what he would focus on if he was given $1 billion.

In this episode, you'll learn about aging in animals and humans and the factors that determine their longevity. You also hear about aging in the private sector as well as  comparing today's interventions to aging with evolutionary stimulus.

Episode Highlights:

• Professor Austad's transition from animal behavior to aging
• The striking differences  in aging between a South American species of opossums and mice
• The rate of living theory
• The constant heartbeat theory—understanding the impact of heartbeat rate and longevity
• An alternative to the rate of living theory—the evolutionary approach
• Professor Austad's study and discovery on the aging of possums without predator interference
• Why birds of flight live longer than terrestrial birds
• Current estimates on bat longevity and why bats have a long lifespan
• How natural history observations can accelerate more molecular or pharmacologic insights into human health
• How evolution is smarter than humans
• Professor Austad's view of the research enterprise
• Aging in the private sector and for-profit aging companies
• Mechanisms in age-related decline
• Professor Austad's bet with Jay Olshansky about a living 150-year-old person by 2150.
• 
  

Quotes:

"The interesting thing is that project was about the sex ratio of the pups and was eventually published in Nature. And by the time it came out, I totally lost interest in that project, and I was off studying aging."

"Evolution has this wonderful capacity to take a single-cell fertilized egg and have it develop into a healthy adult in some kind of species. It would seem to be just much easier to simply maintain that healthy adult once you have it, but yet it's almost ubiquitous that when aging occurs, that healthy adult gradually loses its health."

"One of the evolutionary ideas to understand that was that evolution is all about reproduction, and what evolution will favor is whatever physiology maximizes reproductive rate."

"One of the things about possums that's important to note is that about 80% of them are ultimately killed by predators."

"So it's clear that the lack of predators had really had an impact on those opossums because they were just like the animals of the Galapagos, completely unafraid of humans."

"The longest-lived wild bat is reported to be 41 years. And that's an animal that's about a fifth the size of a mouse."

"High-frequency hearing is one of the first things we lose, but bats have to maintain that year after year after year because getting their food depends on it. They find their animals in the dark by screaming and listening for the echoes. So the fact that a bat can live over 40 years in the wild strikes me as much more impressive than if it lived 60 years in a cave somewhere."

"One of my favorite quotes is that evolution is smarter than you are. I think that's true because it's just so long to experiment. And so I think evolution will have come up with solutions to, let's say, how to maintain muscles better, maintain vision longer, or maintain nerves better in some species than we currently already do in humans."

"I think scientists are increasingly conservative because they want to be able to do something that they know works. And most people I know have at least half of their next grant proposal already done, half the research done before submitting the proposal. And that, to me, is a good recipe for incremental advances, but not a recipe for major breakthroughs."

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Professor Steven Austad LinkedIn

Professor Steven Austad Wikipedia

Dr. Nabiha Saklayen is CEO & co-founder of Cellino, a personalized regenerative medicine company developing an AI-guided laser editing platform for autologous cell-based therapies. Cellino’s proprietary technology aims to make personalized stem cell-derived therapies scalable for the first time. Dr. Saklayen received her Ph.D. in Physics from Harvard University as a Howard Hughes Medical Institute (HHMI) International Fellow.

In this episode, she joins Chris Patil to discuss autologous cell therapy and the strides Cellino has made in cell therapy using Machine Learning and laser technology. Dr. Saklayen talks about the challenges that come with autologous cell therapy, particularly in the manufacturing and cost aspect, and how Cellino infuses automation to make this procedure easier. She discusses how machine learning is integrated in the whole process and gives a brief insight into her career as a physicist and founding Cellino. She rounds up by discussing the future of Cellino and how Cellino strives to provide solutions in cell therapy that would change the world one patient at a time and at low cost.

In this episode, you’ll learn what cell therapy is and how Dr. Saklayen, through Cellino, is reshaping the world of cell therapy and biotech as we know it.

Episode Highlights:

●  What is cell therapy?

●  Defining autologous cell therapies

●  Examining the challenges with autologous cell therapy

●  Cellino as a thought leader in the biotech industry

●  The power of automation and laser therapy

●  How machine learning contributes

●  Dr. Saklayen’s career journey

●  Going from a blood cell to a stem cell -  Sendai virus and  episomal vectors

●  How to determine the success of an IPSC induction

●  The future of Cellino

●  Targeting diseases of aging

●  How Cellino is providing solutions in aging aspects

●  Cell therapies over small molecules

●  Cellino’s goal for the next five years

Quotes:

“Cell therapy is a therapy where you make new cells for the patient and transplant them into the body to change the outcome of a disease or trajectory of a disease.”

“It's about throughput. It's about yield. It's about consistency.”

“The way we automate this process is by using machine learning algorithms that have been trained to look at images of cells and tell us which cells are high quality and which cells are not.”

“It's really amazing to be able to tap into image-based machine learning algorithms and route the autonomous self-driving car industry towards advancing a lot of the neural nets that we're using in our training.”

“I decided I want to be closer to real-world applications.”

“Working together as an industry is going to be very important.”

“Where we'd like to be in five years is we want to have our platform developed to a point where we can generate high quality patient specific cells in a reproducible manner, and do that for clinical doses.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dr. Saklayen's TechCrunch Disrupt Talk

Dr. Saklayen's LinkedIn

Dr. James Peyer, PhD, is the Founder and CEO of Cambrian Biopharma, a Distributed xDevelopment Company developing therapeutics targeting the biological drivers of aging.

Cambrian Biopharma brings together experts, scientists, and experienced company builders in a new model of entrepreneurship related to health span and aging. Dr. Peyer was previously the founder of Apollo Ventures, a successful venture capital firm focused on the longevity biotech space. He has spoken on the topic of longevity biotech and investing for Bloomberg, The Economist, TEDx, Longevity Leaders, ETH Zurich, and the Max Planck Institute on the Biology of Aging.

Today, Dr. Peyer joins host Chris Patil to discuss venture capitalism in the longevity space and the new models that are changing the game. After discussing his previous experiences with VC, Dr. Peyer introduces the Distributed Development Company (DISCO) model, which allows scientists to partner with an umbrella company (like Cambrian) instead of selling their discovery to a pharma company. He explains how this model allows investors to support scientists through the whole process of drug development, from initial idea to commercialization, while prioritizing the quality of the science above everything else. Dr. Peyer then goes on to give some details about Cambrian’s success so far and how it sources and supports up-and-coming talent in the longevity field. He finishes up by making some predictions about the future of biotech companies and how the DISCO model will have a big role to play.

In this episode, you’ll learn about venture capitalism’s role in scientific discovery and development and why Dr. Peyer believes a new model is necessary to remove the inefficiencies in the current process.

Episode Highlights:

·   Dr. Peyer’s experience with Apollo Ventures and why he’s moved on to Cambrian Biopharma

·   The future of the longevity space will come in two stages: reusing insights into what makes us age to build drugs for today, and using those safe and effective drugs to slow down the rate of aging in healthy people

·   In the long run, company-based models will be better than fund-based ones for the longevity space

·   The Distributed Development Company model (aka DISCO)

·   Cambrian started with three programs and has scaled up to over fourteen in two years

·   Cambrian prioritizes the quality of the science over hype

·   Cambrian has raised about $160 million since 2019, including $100 million Series C financing at the end of October

·   Cambrian sources talent through constant monitoring of the scientific field

·   The DISCO model was designed to correct inefficiencies in the process of getting funding for scientists and their discoveries

·   Drug development is a risky process, and Cambrian ensures success by carefully monitoring progress at every stage

·   Being a bona fide longevity biotech organization means being willing to support every single program from funding to commercialization

·   There are opportunities to partner with big pharma companies, but commitment to the whole process is the default

·   Cambrian’s two publicly-disclosed programs are with Vita Therapeutics, a cell engineering company run out of Johns Hopkins

·   One of the advantages Cambrian can provide to scientists is the ability to keep their discoveries as trade secrets as long as possible to maximize their patent lifespan

·   The potential for the DISCO model to be used in other fields beyond longevity

·   The possibility of failure and how Cambrian works to avoid it by being realistic and strategic and bringing expertise on board

·   DISCO works really well for asset-centric breakthroughs made by very small companies or at universities, but it’s not the catch-all solution for everything—for example, tech platforms may be a better choice for bigger biotechs, while founder-led biotechs are better for young entrepreneurs

·   External factors in aging

·   Predictions for the field ten years from now

Quotes:

“I like to say that we get to take the best parts of being a VC, a pharma company, and an entrepreneurial biotech, and very few of the negatives.”

“When we raise capital into Cambrian, what we get to do is we have our Cambrian team, which cares exclusively about the quality of the science, right? Not the hype or the number of Twitter likes around some particular discovery, but exclusively about the quality of the science.”

“Cambrian breaks apart the existing longevity biotech field at the academic level, into thirteen different focus areas that we are constantly monitoring.”

“I think that our model was designed to correct some of the inefficiencies that happen for scientists and scientific founders first, and it also is a happy accident that that model is also, I think, the more investable and more scalable one.”

“Creating an organization that can really assess a group on whether it’s sink or swim based on the science and not the ability to raise money, I think has been a huge advantage for us.”

“The reality of the situation is when a drug starts its first human clinical trial, there is about a 10% chance that it will ultimately make it to approval. And if you select just on, like, venture-backed biotechs from really smart groups, that number only goes up to about 15-16%.”

“With every single program that we get involved with, if the science continues to look great, that means we are going to be there with that group, providing the funding, the organizational structure, everything to see that all the way through to commercialization.”

“The value of any drug is driven essentially by its patent life.”

“Models like the DISCO model that we’re using with Cambrian are actually going to replace a big chunk of early-stage venture capital in the biotech space and particularly for asset-centric companies.”

“I sometimes call this model of biotech, the ‘hungry beast’ model of building biotechs.”

“We’re just much more hands-on, right? We want to be doing the research and development, and the funding, and a lot of the strategy, together with the scientists that we start things with, which doesn’t fit for everybody.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Cambrian Biopharma Homepage

Professor Michael Snyder is the Chair of Genetics at Stanford School of Medicine, where his research group develops and uses technologies to study biological regulatory networks and applies these approaches to understand human variation and health. He's founded multiple biotech startups and has authored a book titled Genomics and Personalized Medicine: What Everyone Needs to Know.

Today, Professor Snyder joins host Bob Hughes to discuss the impact of big data on human health. He reviews the results of his research, carried out on 109 people including himself, which entails collecting numerous types of health data and building an informative data profile, as opposed to the traditional approach of collecting just a few pieces of information. He goes on to share his personal story of how collecting deep data on himself helped him change his lifestyle after being diagnosed as a type two diabetic - using precision medicine to control diabetes. Professor Snyder also explores how DNA methylation can be used to track aging patterns and ageotypes, as well as the relationship between aging and Big Data collection, and also discusses health and longevity from his viewpoint, particularly from the standpoint of boosting the immune system.

In this episode, you’ll learn how Big Data can influence our health, and why Professor Snyder believes that the transformation of healthcare begins with deep-diving into data.

Episode Highlights:

●  Understanding precision medicine and personalized medicine

●  How Big Data influences individual health

●  Professor Snyder’s research results on 109 people

●  The impacts of deep data profiles

●  How Professor Snyder changed his lifestyle after deep-diving into his data

●  Using precision medicine to control diabetes

●  DNA Methylation and tracking aging patterns

●  Selection criteria for the 109 research subjects

●  Professor Snyder’s growth over the years from yeast biology

●  Human health and longevity from Professor Snyder’s viewpoint

Quotes:

“We're actually much more focused, I would say, on precision health, trying to keep people healthy at an individualized level, and trying to use big data to do just that.”

“We're in a world now where you can just collect so much deeper data on people.”

“I liken it to a jigsaw puzzle. If I want to see what the picture is in a puzzle, looking at one or two pieces of a 1000 person puzzle isn't going to tell me the picture, even 15 pieces probably won't do it. But I want to look at as many pieces as possible. And that's what big data is all about.”

“One aspect is to collect data, the other is to do it over time.”

“A lot of people who survived the COVID infections wind up being type two diabetics on a 4% increase, which is a pretty large number of people.”

“Everybody has different aging patterns, and so the way we think about this is like a car. Your car as a whole gets older over time, but some parts wear out first. ”

“Having good biomarkers for aging, we think, is a big deal.”

“Why are we measuring 15 things? We should be measuring thousands.”

“There's a ton of investment going into longevity these days - billions of dollars now into these new startups.”

“Your immune system starts plummeting in your 60s, as I say, and that just leaves you more and more vulnerable anytime after that.”

“I think we can transform healthcare. I think you'll see big changes in the next 10 years in terms of home testing, all this sort of stuff.”

Links:

Email questions, comments, and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

The Snyder Lab

Genomics and Personalized Medicine: What Everyone Needs to Know

Ben Kamens is the founder and CEO of Spring Discovery, a company devoted to accelerating therapies for aging and its diseases. Prior to that, Ben was the first engineer for Khan Academy, which provides free online education to millions of users around the world. Today Ben joins host Chris Patil to discuss Spring Discovery’s mission to increase healthy lifespan and dramatically reduce disease, his experience with Khan Academy and how it connected to his work in biotechnology, and overcoming challenges in the field of aging. 

Ben tells Chris about his pragmatic approach to building a company, how Spring Discovery plans to accelerate drug discovery and clinical development, and their collegial relationship with BioAge and other companies in the longevity biotech sector. Ben chats about Spring Discovery’s recent Series B funding, then offers a sneak peek into their therapeutic pipeline, and details his experience running a nonprofit clinical trial for a generic drug to fight against COVID, including what this taught him about testing drugs for age-related indications. Finally, Ben shares his favorite aspect of longevity science that his company is not currently working on, and where he sees the field of aging moving toward over the next five to ten years.

To learn more about Ben and Spring Discovery’s work to accelerate drug discovery with machine learning, visit springdiscovery.com.

Episode Highlights:

• Ben Kamens is the founder and CEO of Spring Discovery; he was also the first engineer for Khan Academy
• Introduction to Spring Discovery and how recent Series B funding will help the company advance its work to increase healthy lifespan and dramatically reduce disease
• His initial skepticism and passion for fighting disease 
• Overcoming obstacles in the field of aging
• Building value and resources as a company over time
• Accelerating drug discovery and clinical development
• Machine learning approach
• Spring Discovery’s therapeutic pipeline
• Ben’s involvement running a nonprofit clinical trial for a generic drug against COVID, and what this taught him about testing drugs for age-related indications
• You can read Ben’s article “COVID-19 is the latest disease to point at our need to treat immune aging” here
• Favorite aspect of longevity science that his company is not currently working on

Quotes:

“I couldn't think of a more important mission to try to enable than battling diseases of aging. And our mission is to give the best technology possible to these people who are doing what we think is the most important work possible.”

“I came to this field as an outsider and somebody who's really a team builder, and interested in deploying the intersection of scientists and technology to try to fight disease.”

“I am an extremely pragmatic person, especially when it comes to company building and entrepreneurialism.”

“When you mention aging, you're immediately talking about this extremely broad array of biological phenomena, some of which are going to be relevant clinically, some of which are not.”

“This presented a real opportunity to build the best company in the world at measuring the many changes that occur in us as we age.”

“We've essentially taken an engineering throughput mindset to disentangling the many dimensions of age-related changes that accrue in our cells and tissues over time, and built a company around getting really, really good at that, and then using that to much more quickly search for therapies.”

“You can think of it as a big engine that takes in a whole bunch of primary human samples, spits out this very multidimensional, complete view of cellular function, but does it in a big single screen that's combining tons of phenotypic imaging data with proteomics data, and then uses a set of models we built up to identify different cellular functions that are being identified in that raw data.”

“I do not view that as competition whatsoever. I have nothing but respect for BIOAGE.”

“We can cause all sorts of problems for ourselves. I don't really know what a competitor would do that would really dramatically change our trajectory.”

“Our current focus is in the world of immune aging, and specifically how immune aging applies to both the pulmonary and skin therapeutic areas.”

“We were following our standard path. And then, as you know, the more data that came out, the more it became very obvious that, more so than any other comorbidity, one's age defined one’s outcome with COVID. And it was almost looking like people who are much older who get COVID have an entirely different disease than people who are much younger.”

“For most diseases, they are way worse for you if you're older, and so where is all the therapeutic effort that is focused on that huge fact in COVID?”

“I am very uniquely proud that we found a way to do this.”

“For me, this was just validation that there are ways to run pragmatic, cost effective, timely clinical trials for diseases that are exacerbated by the biology of aging.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Spring Discovery Website springdiscovery.com

Rochelle Buffenstein is one of the world’s leading authorities on the naked mole rat, a fascinating animal that has emerged as an important model for research in longevity science. Dr. Buffenstein is currently a senior principal investigator at Calico Life Sciences, a subsidiary of Alphabet, that is seeking to better understand the biology that controls aging and lifespan. 

Today Dr. Buffenstein joins host Bob Hughes to explain why the naked mole rat is such a powerful model of successful aging. She talks about their resistance to cardiovascular disease, cancer, and neurodegeneration, and what this means for improving human health. You’ll hear about the role of Nrf-2 signaling in maintaining optimal health, looking beyond common animal model systems to understand aging more deeply, and the advantages of looking at health and longevity in naked mole rats versus mice. Dr. Buffenstein also discusses the typical hallmarks of aging and inflammation as they present in the naked mole rat, their unusual reproductive activity, and what this can teach us about human fertility. 

In this episode, you’ll learn why this unique and resilient creature is a “super organism” of sorts, and why Dr. Buffenstein believes they contain the blueprint for how to live long and successfully healthy lives.

Episode Highlights:

• Introduction to naked mole rat as a powerful model of successful aging
• How Dr. Buffenstein came to study these animals and what is unique about their aging process
• Naked mole rat’s reduced susceptibility to cardiovascular disease and cancer
• Research on whether they are resistant to neurodegeneration
• Central mechanism that provides generalized protection may be at play
• Nrf-2 signaling pathway and its role in maintaining optimal health
• Thinking beyond common model systems to learn about molecular processes of aging
• Studying aging in a long-lived system is more pertinent to humans
• Advantages of looking at slow aging process in a natural context
• The Methuselah Mouse Prize (Mprize) is being offered to the first person who can make mice live longer than five years
• Ultimate cause of death in naked mole rats is unknown
• Hallmarks of aging and inflammation process as they relate to naked mole rat
• Naked mole rats lack natural killer cells, which are very important for fighting viruses
• Innate and adaptive immune systems
• Unusual reproductive activity for naked mole rats
• They have adapted to a particularly harsh and hostile environment
• Dr. Buffenstein believes they contain the blueprint for how to stave off many of the adverse effects of aging

Quotes:

“A naked mole rat is a mouse-sized rodent that stands out as an especially powerful model of successful aging, primarily because it is known to live an incredibly long time. It seems to be exceptionally resistant to most age-associated diseases like cancer and cardiovascular disease. And even reproductive senescence.”

“We believe that given this phenotype that these animals are a very good example that aging does not need to be inevitable, and that they hold the blueprint for how to live long and successfully healthy lives.”

“I got my first grant, looking at how it is that they're able to live 17 years. Little did I know then that these animals would be exceeding 39 years of age in my care.”

“The fact that these animals don't seem to show any age-related change in cardiac function to me is remarkable. If we could understand the mechanism behind that, we might be able to come up with ways to improve human heart function and human health.”

“[Naked mole rats] seem to be resistant to just about everything.”

“We think that the mechanisms that protect them against aging might be the same as some mechanisms that protect them against cancer as well.”

“We know that broccoli and the cruciferous vegetables all upregulate Nrf-2 naturally.”

“I think the traditional model organisms have played a very important role in understanding aging. Because while evolutionary distance all of these models share an important feature, and that is, as they get older, their health declines and their probability of dying increases.”

“I think that yes, we've learned a lot from mice, and we've learned how we can manipulate aging or health span, to some extent, but nowhere near the extent that you could, by looking at species that have already over a multimillion year evolutionary process, modified their biology and have features that enable them to live 10 times longer than a mouse. And that's where I think the naked mole rats are an important model.”

“The real answer is we don't really know what it is that kills them. We just know what doesn't kill them are the common diseases that kill mice and rodents.”

“Every time we've tried to induce some kind of stress, we see a very abrogated or attenuated inflammatory response. They don't seem to activate their inflammatory pathways to the same extent as other animals.”

“Unlike mice, which have predominantly lymphoid cells, T cells and B cells, naked mole rats tend to rely much more on the innate immune system, on the myeloid cells.”

“Both humans and more rats have about 40% of their immune cells being the slow responding adaptive immune cells.”

“Any female in the colony can breed, but most of them are stuck in the suspended prepubescent state. When a female becomes the dominant breeding female, she continues to breed throughout her life. There's no sign of menopause.”

“In most species, fertility declines as you get older. It's true of mice, and it's true of humans. And yet mole rats are showing the exact opposite pattern where the number of offspring produced in a litter increases with increasing age.”

“The naked mole rat can survive 18 minutes in an oxygen-free environment without damaging its brain in any way. Whereas humans and mice after three minutes are brain dead.”

“I think many of the effects that we see that pertain to their extreme longevity are byproducts of having to cope with such a harsh and hostile environment.”

“The biology of the naked mole rat provides a proof of concept that it contains a blueprint for how to stave off many of the adverse effects of aging. The real problems with trying to figure out what that blueprint is.”

“To me, the next steps are trying to successfully make transgenic naked mole rats, and being able to manipulate certain genes both in them, and giving their unique genetic makeup to mice to see if we can extend their longevity, or at least their health span in a significant kind of way.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Calico Labs Website calicolabs.com

Earlier this year, the University of California San Francisco launched the Bakar Aging Research Institute (BARI), a scientific community that aims to translate breakthroughs in aging research across many disciplines into new approaches and treatments that help people remain healthy and vibrant in later life. Here to tell us about the Institute are Professor Leanne Jones, who moved from UCLA to UCSF to serve as Director of BARI, and Associate Professor and Associate Director of BARI, Saul Villeda. Today Dr. Jones and Dr. Villeda join host Chris Patil to discuss the mission and structure of the Institute, as well as their goal to bring people from different campuses together to push forward the field of aging research as a whole.

Dr. Jones and Dr. Villeda talk about the collaborative culture at UCSF, lowering barriers to resources across disciplines, and what inspired the idea behind the Institute. They explain how they plan to foster communication between basic scientists, clinicians, and healthcare workers to enhance translational medicine, as well as the pathway to commercialization for BARI, and the value of building a community around improving human health together. Finally, Chris asks Dr. Jones and Dr. Villeda about the greatest challenges they’ve had to overcome in starting the Institute, their top priorities moving forward, and what they’re most excited to achieve through BARI over the next five to ten years.

Episode Highlights:

• Mission and structure of the Bakar Aging Research Institute (BARI)
• Responsibilities and benefits of membership in the institute 
• Connecting researchers across campuses 
• Network creation and community creation
• Spirit of community will help attract other institutions to collaborate
• Providing central resources and lowering barriers to research
• What inspired the Institute and founding vision of Barbara Bakar
• How BARI will enhance and promote translational medicine, translational applications
• Improving communication amongst scientists, clinicians, and healthcare workers who are interested in treating problems related to aging
• QB3 is a University of California hub for innovation and entrepreneurship in life science
• Path to commercialization for BARI
• Value of communicating with the community and including everyone in the conversation about improving human health
• Biggest challenges Dr. Jones and Dr. Villeda have had to overcome in getting BARI started
• Building a tangible community through a hybrid system of virtual/in-person interactions
• Top priorities moving forward and what they hope BARI will achieve in the next five to ten years
• Investing in the community and helping people jumpstart their research programs (e.g., Sandler Fellows Program)

Quotes:

“Our mission is broad, and really focused on building networks and community around aging. And, as we've said, improving the outcomes for older adults.”

“It's exciting to think that our original vision of bringing people together from across all of the campuses is really coming to fruition.”

“The requirement is that you're a full-time faculty member or equivalent at UCSF, and membership brings an ability to have first priority for funding opportunities, as well as the core resources that we're building up currently.”

“What we quickly realized is that there are a lot of existing resources that people just don't know about. There was no centralized place, where you could just send an email and say, Hey, is anyone in Geriatrics...collecting blood from aging people?”

“That's really one of the main things I think that people will get out of this - it's sort of a central place where you can make connections to facilitate and push your research forward.”

“We really took it on as our charge to provide all of these resources for the community at UCSF, so that there's really lowering of any barrier to do the type of research that's related to the biology of aging, and also health span, and improvement of health ultimately, within the community.”

“We're starting locally. But hopefully, we'll have an impact beyond the UCSF campuses soon.”

“Really, I think that's the essence of the entire Institute is this idea of community.”

“Here we have an institution where everyone is so close to each other, they have all the expertise, that just by building a series of bridges, I think we'll have an entire roadmap from beginning to end.”

“We are improving the ability of everyone to take their discoveries, and hopefully have a much wider and a much more long lasting impact.”

“We're really leveraging some of these resources to both facilitate questions that people have wanted to ask for a long time, but maybe didn't feel that they have the support to do it.”

“We decided then that an institute would be the best way to sort of transfer this idea of community in a very tangible way across UCSF.”

“In terms of infrastructure, we're trying to already lay the groundwork for setting up a program to do translational studies.”

“We've got basic biologists, clinicians talking already, we are providing resources and funding for collaborative studies between these groups. And we're trying to go ahead and think about how we can provide a framework for translational neuroscience at UCSF.”

“UCSF is a public university, and our mission is human health. And we want to be able to interact with and connect with the community.”

“One thing that worked in our favor was actually the fact that we have been virtual for almost two years now, and that facilitated a number of town halls.”

“What I'm really hopeful that we will be able to do is to be a place where an individual can come to get a personalized plan for improving their health or for maintaining their health.”

“Every time you bring in someone new, it changes the landscape. So that makes me excited.”

“I have no doubt the seeds that we are planting and sowing right now will really prove to be fruitful in the next five years.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Bakar Aging Research Institute (BARI) Website geroscience.ucsf.edu

Gene therapy screening to discover aging targets (Martin Borch Jensen -  Gordian Biotechnology)

Gordian Biotechnology is a San Francisco Bay Area biotech company that has created the first in vivo therapeutic screening platform aimed at drug development for complex diseases of aging. Co-founder and Chief Science Officer, Dr. Martin Borch Jensen joins the show today to discuss Gordian’s unique in vivo pooled screening in animals, as well as which indications they are targeting, their strategy to bring drugs to market, and how Gordian is currently tackling the challenges inherent to animal models. Martin also speaks about his passion from an early age to help fight age-related disease, and making the transition from academia to entrepreneurship, giving up a K99 fellowship at the Buck Institute for Research on Aging to make the jump into biotech.

You’ll also hear about Martin’s involvement in multiple efforts to promote longevity science and bring new people into the field, including his apprenticeship program, the newly announced Longevity Impetus Grants program, and recording his “Science of Aging” seminar. Next, Martin shares what’s next for Gordian as they get ready to scale to the next level, which areas of longevity science he is most interested in but not currently working on, and how he predicts the field will evolve over the next five to ten years. For more information on Martin’s apprenticeship program and Impetus Grants application process, please visit MartinBorchJensen.com or follow him on Twitter.

Episode Highlights:

• Dr. Martin Borch Jensen is the co-founder and CSO of Gordian Biotechnology
• Gordian Biotechnology created the first in vivo therapeutic screening platform to radically improve drug development for complex diseases of aging
• Martin is also involved with an apprenticeship program and a newly announced grant program to catalyze rapid progress in aging research
• How Gordian’s unique in vivo pooled screening in animals works
• They’re focused on removing the diseases of aging, beginning with their three lead indications, NASH (nonalcoholic steatohepatitis or fatty liver), osteoarthritis and idiopathic pulmonary fibrosis
• How Gordian compiles their gene libraries
• While other companies start with in vitro models and then figure out ways to test them in living animals, Gordian starts with the second step 
• They deliver hundreds of gene therapies at once to a single animal
• The drugs that they ultimately develop won't necessarily be gene therapy, but instead whatever is most appropriate to pursue the indication once they know the target (small molecule drugs, antibodies)
• What a cell needs depends on what a cell is
• Gene therapy has plenty of advantages, but the cost is very high
• How Gordian is overcoming challenges that are inherent to animal models
• Older mice are much more expensive and are rarely used in aging research
• Animal models can actually be useful if the animal has progressively developed a disease in the same way humans do, and has similar biology
• Example of studying osteoarthritis in horses, because the load-bearing structure of their joints is much more similar to humans, as is their cartilage thickness
• Gordian’s strategy to bring drugs to market
• Martin’s transition from academic to entrepreneur and what inspired him make the jump to biotech
• He gave up a K99 fellowship at the Buck Institute for Research on Aging
• He realized as a teenager that he wanted to try to fix aging
• Martin is good friends with Dr. Kristen Fortney, co-founder and CEO of BIOAGE; her journey showed him that it was possible to start his own company
• Martin is also involved in multiple efforts to promote longevity science, and to bring people into the field
• His apprenticeship program was developed as a way to bring people in, and train them to be able to work on direct projects
• Longevity Impetus Grants is a $21 million (update: $26 million as of the release of the podcast) program that provides funding for scientists to start working on what they consider the most important problems in aging biology without delay
• This was inspired by COVID-19 “Fast Grants,” created by Tyler Cowen, Patrick Collison, and Patrick Hsu
• Their goal is to take big bets on projects that could move the field forward, and recipients will be able to publish their findings regardless of what their results are
• Impetus Grants applications open on Monday, September 13, 2021
• Martin also recorded a comprehensive seminar about the science of aging
• What’s next for Gordian as they get ready to scale to the next level
• Martin predicts that in 5-10 years, we will have ways of measuring biomarkers for aging in humans

Quotes:

“It's phenotypic screening, but also because it's gene therapies we're putting in, we know the target immediately. So I call it ‘pheno-target screening,’ combining the best of both discovery modalities that are used.”

“At Gordian, we're focused on removing the diseases of aging. Right now we're doing that with three lead indications, and that number will grow, which are NASH and osteoarthritis and idiopathic pulmonary fibrosis.”

“We've created the platform in order to be able to do somewhat unbiased screens or entirely unbiased screens, and just explore a lot more of the biology of these diseases than has ever been explored in vivo so far, because we have this higher throughput.”

“The logistics of the other method simply don't allow you to test a wide range of things in the in vivo context.”

“I'm very excited about gene therapy in the long run to treat aging, diseases of aging, and just the physiological processes of aging. Because it turns out that what a cell needs depends on what a cell is. And so you probably don't want the same treatment in every type of cell in your body.”

“You need a targeted way to go in and give each type of cell and each tissue what it needs, if we're going to really exercise control over the aging process.”

“Maybe animal models aren't so bad for many diseases, if you find an animal that has continuously developed, progressively, a disease in the same way that humans develop this disease, and has biology that resembles human biology and the relevant organ.”

“We are a drug development company. We've developed this in vivo full screening platform in order to use it ourselves and discover the best drugs for each of the indications that we go into.”

“We are in conversations with a whole bunch of pharma companies about partnering at the clinical stage around the assets that we are discovering with our platform.”

“As a teenager, I came to the realization that I wanted to try to fix aging… The idea that everyone is going to get sick and be in pain, and then die, just seemed really bad.”

“I wanted, with Gordian, not only to have the successful outcome of treating age-related diseases, but I also wanted to feel for myself that I was doing absolutely everything that I could towards the goal that I had decided.”

“It's going to be really hard. There's going to be doubts and challenges… And so if you're doing it for reasons that won't compel you to push through all of that, it's probably not going to work out.”

“[This apprenticeship program] is needed, because there are more things that should happen, and apparently could happen, than I could possibly ever go and do myself.”

“The apprentices end up doing most of the legwork by far. And I'm kind of steering it.”

“This is the real test of success for this apprenticeship - if the people in it end up running important projects within the longevity field overall, then it's a success.”

“If there is something there, if the project does work out, that would actually be a really big push forward for the field, then we should try to fund those things. And many of them won't work out and that's okay. We can learn from that.”

“Any nonprofit can apply from anywhere in the world. Or any researcher at a nonprofit.”

“What you really have to explain to us is, How is what you're doing going to move the field forward, if it works, and why is the way that you're doing it, a good, robust, well thought-out experimental plan for doing it? Those are the main things that we look for.”

“In five to 10 years, I think we will have drawn studies for biomarkers of human aging. So I think that in five to 10 years -hopefully more like five - we will have ways of measuring in humans, something that we choose to call aging.” 

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Martin Borch Jensen Website MartinBorchJensen.com

Martin Borch Jensen on Twitter: @MartinBJensen

Longevity Impetus Grants Website ImpetusGrants.org

Gordian Biotechnology Website Gordian.bio

On today’s episode is Dr. Jennifer Garrison, Professor at the Buck Institute for Research on Aging, and the Faculty Director of the Global Consortium for Reproductive Longevity and Equality (GCRLE), which is devoted to supporting breakthrough research on reproductive aging and women in science through funding, training, infrastructure, and collaborative intellectual networks. 

Dr. Garrison explains that while there are plenty of scientists working on aging and plenty who are working on reproductive biology, there are precious few who are working at the interface of these two fields, which is what they are trying to build at the GCRLE. She shares her fascination with ovarian biology and how it fits into the broader context of longevity research, and details the issue of equality in terms of women having to plan their life choices around reproductive longevity in ways that men do not, as well as funding for women’s health being traditionally overlooked. Dr. Garrison answers questions about menopause across the animal kingdom, the link between reproductive span and lifespan in women, and the most important question we need to answer in order to truly understand ovarian aging. 

Dr. Garrison describes the key role played by the brain in reproductive success, the need for better animal model systems to understand menopause, and how hormone replacement therapy can help mitigate the negative health consequences around menopause. You’ll also hear about the profound economic and societal impact of menopause globally, as well as Dr. Garrison’s goals for the future and dream outcomes she envisions for the Consortium as they continue their cutting-edge research on the causes of ovarian aging. To learn more about their important work, visit BuckInstitute.org/gcrle/.

Episode Highlights:

• The goal of the Global Consortium for Reproductive Longevity and Equality (CGRLE) is to extend the female reproductive span
• The Global Consortium began at the Buck Institute for Research on Aging through a generous donation from Nicole Shanahan and the Sergey Brin Family Foundation
• There are plenty of scientists working on aging and others who are working on reproductive biology, but precious few who are working at the interface of those two fields - that’s what they are trying to build
• The GCRLE has three arms: Funding; providing resources to build out the field; and building a network communications platform to foster dialogue and collaboration among researchers working on female reproductive aging
• They’ve also opened the world’s first ovarian biology core facility at the Buck Institute
• Ovaries are a very complex structure, and they age at a precocious rate - they’re considered geriatric by the time a woman is in her late 20s, early 30s
• Nicole Shanahan’s became involved with starting the CGRLE to find out what causes ovaries to decline in function so early
• Ovarian biology as it relates to reproductive longevity has been traditionally overlooked in terms of receiving funding
• Women’s health has been looked at as a subcategory of medicine
• Equality is a key piece to what they do - women need to plan their life choices around reproductive health in a way that men do not
• Menopause accelerates the aging process
• It is relatively rare in the animal kingdom - humans are one of the only species that go through menopause
• Women who experience menopause later in life also tend to live longer and have an enhanced ability to repair their DNA
• There is a clear link between reproductive span and lifespan in women
• The key question is, What is the cue that tells a woman’s ovaries to start declining in her 20s?
• The brain is a crucial player in reproductive success
• We need better animal model systems to understand menopause
• Female reproductive health trajectory and how medical intervention fits in
• Hormone replacement therapy is one of the best band aids we have to mitigate the negative health consequences of menopause
• Studies show that there is a positive benefit to doing hormone replacement therapy on cognitive function
• Economic impact of menopause and related healthcare costs
• Emerging trend of reproductive aging in biotech industry
• Dr. Garrison’s goals for the future and dream outcomes she envisions for the Consortium

Quotes:

“We started a few years ago, with a really generous gift from Nicole Shanahan and the Sergey Brin Family Foundation. We started a center at the Buck Institute to study female reproductive aging.”

“When we started the center, we realized right away that if we really wanted to have an impact, and truly move the needle, that we were going to have to do something bigger. And that's where the consortium came in.”

“What's different about the ovary, compared to every other organ in the human body, is that it ages precociously, meaning that it's actually the first organ by far to age in the human body, and it's aging at about two and a half times the rate of the rest of the tissues.”

“I think research on women's health is underfunded in general.”

“I think that as we make progress and advances in extending healthy longevity and health span, or the number of years that someone's healthy, if we don't address reproductive longevity, then I think gender inequality is going to get worse, not better.”

“From the minute I went through puberty, whether I wanted to have biological children or not, every decision that I made was overshadowed by the fact that I was going to go through this reproductive decline in midlife - this biological clock, so to speak, that was ticking in the background. Decisions about overall health, my career, family planning. This is an issue of equity. Men don't have these concerns.”

“Humans are really weird. We're very unusual as a species. There's almost no other species - there's very few species that go through menopause.”

“Women who have later menopause tend to live longer. They also have an enhanced ability to repair their DNA.”

“There's no question that the brain is a key player for reproductive success. It controls all aspects of female reproduction: Puberty, menstruation, fertility, conception, pregnancy, childbirth, childcare, and ultimately menopause.”

“That's the goal is to give women more choice and control over their own bodies.”

“By the time a woman actually might want to use her ovaries, she's left with approximately 2 to 3% of the number of eggs that she started with.”

“The bottom line is that hormone replacement therapy is probably the best band aid we have to mitigate the negative health consequences of menopause.”

“I think the basic science has to happen first. I can't emphasize that more strongly. Otherwise, like I said, everything we're doing is a band aid.”

“I really want people to think about a scenario where women aren't constrained by an immutable biological clock, to think about a world where women aren't subject to the detrimental health effects of menopause. And just to consider for a moment, the implications for social, economic and personal empowerment, that that freedom of choice and freedom from health risks would give to half the population.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Global Consortium for Reproductive Longevity and Equality Website buckinstitute.org/gcrle/

Garrison Lab Website garrisonlab.com

Dr. Hanadie Yousef is a scientist, aging biology expert and the co-founder and CEO of Juvena Therapeutics, a Palo Alto-based biopharma startup developing protein-based therapeutics to promote tissue regeneration and increase healthspan to prevent, reverse, and cure degenerative diseases. 

Dr. Yousef joins host Dr. Chris Patil to discuss Juvena’s premise, their use of a machine learning platform to identify proteins that have therapeutic potential, and what most excites her about turning signaling proteins into therapeutics. She answers questions about handling potential challenges within Juvena’s approach, their strategy for bringing drugs to market, and the first aging indication that they are targeting - muscular rejuvenation. Dr. Yousef outlines Juvena’s plans for a clinical study in patients with Myotonic Dystrophy Type 1 by 2023, and shares what’s coming down the pipeline next for her team. You’ll also hear about Dr. Yousef’s transition from academic science to becoming an entrepreneur, her involvement with the On Deck initiative, which seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field, and why it’s so worthwhile to invest in anti-aging science.

The interview concludes with Dr. Yousef’s advice for potential new founders in the biotech industry. She also shares the areas of longevity science that she is most fascinated by, and offers her thoughts on how the field of aging pharma will evolve over the next five to ten years.

Episode Highlights:

• Tissues deteriorate as we get older and our ability to heal slows down - this leads to a wide variety of age-related diseases
• Juvena Therapeutics sets out to find regenerative cures for those diseases
• During the aging process, critical regenerative protein signaling pathways that are important for instructing cells and tissues within our bodies start to change
• They start becoming over-expressed or under-expressed
• There is a change and loss of healthy crosstalk between pathways that can instruct cells
• This leads to a loss of tissue homeostasis
• By understanding what is changing within us, we can use that information to target protein signaling pathways that are important for stem cell function, immune cell function, etc. in order to rejuvenate tissues and reverse the aging process
• Juvena uses a machine learning platform by combining several data modalities
• Their premise is to develop protein-based therapies that can target critical regenerative signaling pathways in our bodies to promote better regeneration
• They do this by mining secretome of the most po-regenerative source of cells, which are human embryonic, or pluripotent, stem cells
• Aging models that they use are cells derived from people who are themselves aged or who have an age-related disease
• There are challenges with every therapeutic intervention targeting the biology of aging 
• Juvena’s strategy for bringing drugs to market and the first aging indication they are targeting
• They are looking to promote tissue-specific rejuvenation, for example, better muscle differentiation, reduced atrophy and improved strength and function
• They are hoping to have FDA approval as an investigative new drug within the next year and a half - this would lead to a Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 by 2023
• Dr. Yousef’s academic background and transitioning to starting her own company
• She has a passion for both drug discovery and taking those inventions to build companies
• The inspiration and motivation behind starting Juvena Therapeutics with co-founder Dr. Jeremy O'Connell, as well as the process of pitching and acquiring funding
• Dr. Yousef was torn between an academic career and entrepreneurship, and she ultimately decided to embrace her role as CEO and focus on building the company
• How investors react to Juvena Therapeutics’ aging focus and how Dr. Yousef puts their minds at ease with regards to the expense of biotech and therapeutic investment
• It’s worth the risk - with a looming healthcare crisis of an aging population around the corner, the company that succeeds in anti-aging science could be one of the most lucrative and successful companies in the world
• Dr. Yousef’s involvement in the On Deck initiative - a fellowship program that seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field
• Advice she would give new entrepreneurs in this field
• She is fascinated by the study of human centenarians, reproductive aging, and plant aging
• Her predictions for the field of aging pharma in the next 5-10 years

Quotes:

“As we all know, tissues deteriorate as we get older, and our ability to heal slows down, which leads to a wide range of age-related diseases. So Juvena Therapeutics sets out to find regenerative cures for these disorders.”

“Through years of dedicated research, we discovered that the cures had been within us all along.”

“By understanding what is changing within us, we can actually use that understanding to target those protein signaling pathways that are so important in regulating stem cell function, immune cell function, tissue regeneration and repair, in order to rejuvenate tissues, and to actually reverse the aging process and to bring our bodies back internally to a more healthy state.”

“Ultimately, our premise at Juvena is to develop protein-based therapies that can target these critical regenerative signaling pathways in our bodies to promote better regeneration.”

“What we're doing with our machine learning enhanced platform is really building a map of regenerative protein biology with a compounding database that's enabled by an array of in-house machinery and computational tools that we establish using these data modalities, to really identify the proteins that have therapeutic potential.”

“What excites us about actually turning signaling proteins into therapeutics is their ability to really interact in more of a systems biology level with multiple pathways.”

“Of course, ultimately, the goal is to calibrate homeostatic levels of signaling to more youthful levels, and not try to over induce any one particular pathway. And so by really recalibrating, and being careful about dosing, we'll be able to avoid things like oncogenic transformation.”

“We are, right now, really interested in bringing our muscle regeneration protein therapeutic to market for a rare neuromuscular, muscle wasting disease, known as Myotonic Dystrophy Type 1.”

“Our hope is that by 2023, we will be conducting what would be a combined Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 to test if our regenerative therapeutic can, in fact, do what it's doing in all the models and all the preclinical data to date.”

“What's really coming is our ultimate goal of enhancing and promoting health span, and reversing multiple age-related and chronic diseases by developing a pipeline of protein therapies that act by rejuvenating your own body endogenous stem and precursor cell function to enhance regeneration and improve and rejuvenate your life.”

“I am a neurobiologist, stem cell biologist and aging biologist by training.”

“What came first for me was really a passion in general and biomedical research, and in the startup environment and in building companies.”

“I really fell in love with the concept that actually understanding the mechanisms driving the aging process, and specifically, the changes in signaling that occur that lead to loss of stem cell function with age, we can actually use that understanding to reverse the process, to rejuvenate stem cell function to revitalize the body, and to then really reverse aging. And so that got me so excited. And I just fell in love with that and knew that that is what I want to dedicate the rest of my life to doing.”

“It was this battle for me of, I love my research, I can really envision myself leading an academic lab and a faculty position to move this forward, really focus on brain aging. But then there was this also entrepreneurial opportunity to start my company and to instead really focus more on translational work, and really building the platform that enables a pipeline of protein therapeutics.”

“The other things investors fear is just the expense associated with some of these indications.”

“In the next decade, the largest demographic of people will be those over the age of 60. I think it's really in investors that just realize, it's worth the risk. Because the company that succeeds will be potentially one of the most lucrative, successful, and sought-after companies in the world.”

“Some advice I wish I had going into this is really looking at what the target product profile of a drug you want to develop is, and as early as possible, creating a plan to really get to that preclinical stage in that translational stage where you need significantly more investment.” 

“I think in five to ten years, we'll get increasing acceptance of aging as a risk factor to diseases and more of an acceptance of therapeutics that can target the aging process.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Juvena Therapeutics website

The Dog Aging Project is an innovative initiative that brings together a community of dogs, owners, veterinarians, researchers, and volunteers to carry out the most ambitious canine health study in the world. The goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence aging, and to use that information to help pets and people increase their healthspan, the period of life spent free from disease. 

Co-directors Dr. Daniel Promislow and Dr. Matt Kaeberlein join the show to discuss the origins of the Dog Aging Project, the overall goals for their initiative, and why dogs are a particularly good model for human aging. They talk about their funding through the National Institutes of Health, the extensive scale of the Dog Aging Project, and its “Community Scientist” component, with canine participants still living at home with their owners. Professors Promislow and Kaeberlein explain their use of molecular biology measures to predict health outcomes for dogs, their commitment to making their data available to the scientific community as a whole, and the difference between how small dogs versus large dogs age, as well as what diseases or conditions different breeds age and die from.

Today’s fascinating conversation also touches on the impact of living in a rural versus urban areas on aging, how veterinarians feel about participating in the Dog Aging Project, the test of rapamycin in aging dogs (TRIAD), and the intrinsic value of being able to increase the lifespan and healthspan of our pets. Professors Promislow and Kaeberlein share what drew them to the field of aging, and review the importance of putting safety first in their work with dogs. Finally, you’ll hear their exciting predictions for what we can expect to see in aging research over the coming decades.

For more information on the Dog Aging Project, visit DogAgingProject.org. Thank you for listening.

Episode Highlights:

• Professors Daniel Promislow and Matt Kaeberlein are co-directors of the Dog Aging Project at the University of Washington in Seattle
• Dog Aging Project started in 2007 to investigate whether IGF-1 was associated with aging for dogs
• Chief Veterinary Officer is Kate E. Creevy
• Overall goals are to understand how genes, environment, and lifestyle shape healthy aging in dogs and the mechanisms by which they do so, and to determine whether we can intervene and improve healthy aging in dogs
• Dogs are a very good model for human aging due to their similar environment (water quality, air quality, home setting)
• Dogs age seven to 10 times more rapidly than humans do, which means we have better success carrying out longitudinal studies with them
• They also get the same types of diseases that we do
• The Dog Aging Project is funded through the National Institutes of Health, and in particular, the National Institute on Aging
• The scale of this project is notable, as well as the fact that the dogs are not in laboratories, but are living at home with their owners
• It’s a “Citizen Scientist” or “Community Science Project” effort
• They now have upwards of 32,000 owners and dogs participating, and are still enrolling at DogAgingProject.org
• They collect information about the dogs’ health, disease, activity, diet every year, over the course of their entire lives
• These molecular biology measures will allow them to predict what might happen in the future for dogs, and to improve diagnosis and prognosis
• The samples are also stored in a biobank at Cornell, with the hopes that can be useful in studying overall aging as time goes on and new technologies become available
• The Dog Aging Project has always been an open science project, with data being made available to the scientific community on an annual basis
• The rate of aging for dogs varies depending on size and breed
• Biological aging is faster in dogs than in humans, but the relationship is not necessarily linear
• What different breeds die of is very different
• Large dogs frequently die of Osteosarcoma, which is rare in smaller breeds and humans
• Certain organs may age faster than others
• The Dog Aging Project is able to control for different breeds using their genetic data
• Dogs who live in rural areas spend more time outside and engage in more physical activity - soon we will be able to tell how this affects the aging process
• Veterinarians are very enthusiastic about participating in this study
• Test of rapamycin in aging dogs (TRIAD) clinical study looks at whether or not the drug Rapamycin can slow aging and increase healthy lifespan in dogs
• Translating this to humans and bridging this to human trial
• If they find success in increasing the healthspan of people’s pets, this could really change the way the field is perceived by the general public
• Challenges of collecting and curating massive amounts of data
• Dogs who were administered rapamycin became more active afterward
• How Professors Promislow and Kaeberlein became interested in the field of aging
• Dogs are becoming increasingly important models for understanding human health
• Safety is always first priority for the animals
• Professors Promislow and Kaeberlein share their predictions for aging breakthroughs and challenges in the coming years
• We will see advances in biomarkers or “precision geroscience” in the next decade
• It’s important to have realistic expectations and use consistent language when discussing aging - to use the term “curing aging” or “defeating aging” is misleading 

Quotes:

“Dogs experience pretty much every aspect of the human environment.”

“Dogs have the advantage, from the perspective of trying to understand aging, that they age about seven to 10 times more rapidly than people do. So that means that we can actually carry out longitudinal studies to understand the most important genetic and environmental risk factors in a few years, whereas in people it would take a few decades.”

“A lot of what we know about human health and disease, we’ve learned from really simple organisms, like yeast, and nematode worms, and fruit flies.”

“There is no upper limit. We hope to continue this project for many generations of dogs.”

“The first, most important level is just to collect the information about health, disease, activity, diet from all the dogs. That's done through surveys, and all participants will be asked to contribute survey updates every year, so we follow the dogs throughout the course of their lives.”

“Our scientists will also analyze what we call the Systems Biology Components - the epigenome, the microbiome, the metabolome. We're also looking at a panel of inflammatory markers, measuring frailty. So these are the sorts of things that we will track throughout the course of the life of these dogs. The hope is that these molecular biology measures that we collect will allow us to predict what might happen in the future for dogs and to improve diagnosis, and prognosis as well.”

“Our expectation is that the samples that are collected and stored in the biobank will be useful to the field for exploring those other types of molecular markers that may be particularly predictive for overall aging, or certain age-related disease processes.”

“The Dog Aging Project, from its inception, has been envisioned as an open science project. And so all of the data that we collect is being made available on an annual basis to the scientific community.”

“The other thing about dogs is that a decade from now, when new technologies may be available, that's about the equivalent of 70 years of biological aging in people. So it's almost as if any human longitudinal study you had biobank samples for seven decades, we can get that sort of biological age resolution in a single decade of dogs.”

“A Great Dane would be considered geriatric at seven years, whereas a Chihuahua might be considered geriatric at 12 or 14, and could very well live 18 or 19 years.”

“The Dog Aging Project will eventually be able to tell us what the relationship is between the epigenetic age clock and actual aging of pathophysiological processes.”

“There's just a lot to learn about how quickly different breeds age and what they age and die from.”

“We shipped a kit to an owner to take to their veterinarian. And these kits are filled with, as I mentioned earlier, blood samples, hair, fecal samples, urine, and then they need to be delivered via FedEx, to our diagnostic lab. This was a rural veterinarian, and there wasn't a FedEx Office or drop-off point in that community. So the veterinarian, not the owner, but the veterinarian after work, drove 40 minutes to the next town over where there was a FedEx drop-off, so that they could deliver the kit. That's the kind of enthusiasm that we see from participating veterinarians.”

“TRIAD is the Test of Rapamycin in Aging Dogs. That’s the only clinical trial the Dog Aging Project is carrying out right now. And the goal of that trial is really to test whether or not the drug Rapamycin can slow aging and increase healthy lifespan in dogs.”

“Everybody on the Dog Aging Project team agrees that this isn't only about what we'll learn about human aging. There's intrinsic value in being able to increase the lifespan and healthspan of our pets. There's value to the pets and there's value to the owner.”

“I think if we're successful in showing that it is possible to increase healthspan in people's pets, that will really be a watershed moment in the field in the way that we are perceived by the general public.”

“There are lots of wearable devices on the market for dogs. And they're very much like the devices that humans were, typically though they go on the collar of the dog. And we will be putting those devices on the Precision dogs and the TRIAD dogs to measure their activity, how it changes with age.”

“There are several companies now that are trying to develop therapies to treat aging or age-related indications with companion animals, at least as the first path to the market. Me personally, I think that's fantastic. Certainly, we view the Dog Aging Project as something that hopefully other people in the field will build off of.”

“We would just want to encourage all of the companies that are considering moving forward in the companion animal space to keep that in mind, and make sure that whatever you are planning to bring to the market, that you do it in the context of safety. Because the last thing that any of us want to do is harm somebody's pet.”

“We're excited to try and recruit these diverse populations to the Dog Aging Project, and maybe even to use that as a model for getting all communities excited about participating in this term that we'd like to use of ‘community science.’”

“I fully expect that within the next decade, we will see the first geroscience intervention approved to treat an age-related indication.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Dog Aging Project Website DogAgingProject.org

Loyal is a San Francisco-based startup that is seeking to treat the underlying causes of aging in dogs. Loyal has raised $11 million in seed funding so far, and is planning to start clinical trials of medications in 2022 and 2023. In this episode, BioAge VP-Media Chris Patil talks with Celine Halioua, CEO and founder of Loyal.

Celine beginswith by describing the striking difference in lifespan among the dog species, with smaller breeds like the Chihuahua living twice as long as larger breeds like the Great Dane. She explains how historical inbreeding to create larger dogs actually caused them to age faster, and her plan to develop a drug that compensates for this accidental genetic disorder. Celine tells us about The Healthspan Study, which tracks aging markers in dogs, as well as what inspired her to start Loyal, and how their research complements the goals of the University of Washington Dog Aging Project. Celine breaks down the role of caloric restriction in anti-aging across species, why dogs are one of the best models for human aging as a disease, her background in neuroscience and longevity, and her passion for developing drugs for healthspan and lifespan extension. Celine also offers her perspective about encountering skepticism in the biotech industry, the unique challenges faced by young women founders, and overcoming sexist assumptions following the controversial story of Elizabeth Holmes. Finally, Celine shares what’s next for Loyal and her dream to build a consumer-focused pharmaceutical company that people love.

To learn more about Loyal and their dedication to aging health for dogs, visit LoyalForDogs.com. 

Episode Highlights:

• Loyal is seeking to determine why, on average, the larger a dog breed is, the shorter their lifespan
• We do not see a 2X lifespan differential among varieties of other animals
• Loyal also looks at ways to pharmacologically improve metabolic resiliency and fitness in aged animals to give them a longer, healthier lifespan
• Historical inbreeding to create larger dogs led them to age faster once they were fully grown
• Loyal is developing a drug that plans to compensate for this accidental genetic disorder
• These drugs will enter clinical trials in 2022 to 2023
• Loyal is also running “The Healthspan Study,” which tracks aging markers in dogs (register your dog here)
• Dogs are like family to their owners, and Celine noticed how heartbroken owners were about their larger dogs aging and dying so early
• This inspired her to start Loyal
• Distinction between healthspan versus simply adding years to life
• Thesis of Dr. Matt Kaeberlein of the University of Washington’s Dog Aging Project 
• Most breeds have some sort of predisposition for some sort of disease
• LOY-001 specifically targets a cellular mechanism that is hypothesized to cause large and giant breed dogs to age faster and have shorter lifespans than their small-breed companions
• They are also developing a second drug that is explicitly for dogs of any size, who have already shown signs of aging
• Caloric restriction is one of the most fundamental agents of fighting aging - Loyal aims to replicate that effect with a drug, since most humans and dogs do not want to calorically restrict themselves
• Veterinary drugs need to be approved by the Veterinary FDA (Center for Veterinary Medicine or CVM)
• Dogs are one of the best models of human aging as a disease because they’ve largely evolved in the same environment as humans
• Because dogs have a shorter lifespan than we do, we can see whether longevity-based drugs have an impact on lifespan more rapidly than in an animal with an 80-year lifespan (like humans)
• Loyal has raised $11 million in seed funding - the largest amount for a woman solo founder
• Her goal is to show that pharmacological interventions to extend lifespan and healthspan are incredibly valuable and worthy of investment
• She has encountered skepticism in terms of both operational and societal barriers
• Going against the current helps her company stand apart in startup culture, which has been beneficial for recruiting an amazing team, 70% of which is female; but she also has to go above and beyond to prove her competence
• What’s next for Loyal and building a consumer-focused pharmaceutical company
• If they can succeed in developing a dog aging drug, it can help humans as well
• False fail risk
• The aging industry has a communal feel, rather than competitive, as we’re all pioneers in the field and individual successes are everyone’s success

Quotes:

“Fundamentally, we're developing various drug products that are targeting various concerned mechanisms by which dogs age to try to give them healthier years.”

“Specifically, our first two products are looking at one of the underlying reasons as hypothesized why smallest dogs like a Chihuahua can live 18 or more years, while Great Danes on average will live seven to eight years.”

“The larger a dog is, on average, the shorter that breed’s median lifespan, and that's abnormal. We don't see a 2x lifespan differential in humans, for example, or really any other species.”

“It's actually a consequence of historical inbreeding of dogs, that was selecting for certain phenotypes like size, that basically looks to have created almost a genetic disorder for aging in these dogs.”

“The drug that we're developing is hoping to compensate for the accidental genetic disease that we gave these dogs that causes them to become larger...and causes them to age faster after they're fully grown.”

“We are basically doing a cross-sectional, observational - that means no drug, no intervention - study, looking at large and small, old and young dogs. And the idea of this study is basically to correlate various aging biomarkers of interest for our drug programs, and also just out of interest in general, to various dog sizes, breeds and conditions.”

“There are different flavors of dog owners. But in general, people love their dogs. They see their dogs as family. They see their dogs as their furry children in some ways.” 

“Our first drug, LOY-001, is specifically indicated for large and giant breed dogs and extending their lifespan and healthspan and intervening while the dog is healthy.”

“Caloric restriction is one of the most fundamental agent interventions there is. So the question is more, How do you emulate that with a drug? Because obviously, people don't really want to calorically restrict themselves or calorically restrict their dog.”

“It's commonly accepted in the field that dogs are one of the best models, if not potentially the best model of human aging as a disease.”

“Because dogs have a shorter lifespan than we do, if longevity-based drugs are efficacious in dogs, we could see whether they have an effect on lifespan much more rapidly in an animal with a 15-year lifespan than in an animal with an 80-year lifespan.”

“Really my thing from, basically when I was 18, was how to develop better medicines for the worst diseases. And the worst diseases that I have always focused on, and been most interested in, were age-delayed diseases.”

“I felt very strongly that my goal was to explicitly develop a drug for healthspan extension and lifespan extension.”

“It's really fundamentally what I'm trying to do is prove a point to the broader population, to the medical community, to the development community, that yes, pharmacological interventions to extend lifespan and healthspan are incredibly valuable, and worthy of investment.”

“I think when I walk into a room, there’s not necessarily an assumption of competency. And I've definitely also felt a requirement of almost like perfection.”

“I'm very careful with how I word things because it's very easy, especially as a female founder, to get labeled as cocky or overconfident. So I'm much more conservative in my language than I might naturally be.”

“Basically, people don't have very positive emotions or feelings towards pharmaceutical companies, which is understandable on some variables, but also disappointing because I think we want people to be excited about spending time...and working on developing new medicines. It's, in my opinion, one of the most important things to spend your life on because health is fundamental.”

“I'm really interested in the opportunity of building a pharma company that people love.”

“Actually if you think about it, aging encompasses probably the majority of cancers, plus nerve center disorders plus sarcopenia, arthritis, all these other diseases.”

“Honestly, every company that's legitimate, that works on aging is only more helpful. It makes my life a little bit easier to prove that it's a valid thing to work on.”

“We all win if we develop better medicines, and that's kind of where it's supposed to go.”

“I feel like my only job is to help develop better medicines. So it means everything to me because I think it's the most important problem to work on.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Loyal website LoyalForDogs.com

Dr. Ashley Zehnder is the co-founder and CEO of Fauna Bio, a San Francisco, Bay Area-based company founded in 2018. Fauna Bio has adopted a fascinating strategy for drug development, studying animal genomics to cure human diseases. They use unique and varied proprietary data sources to identify novel drug targets across a range of clinical applications, beginning with cardiovascular protection. Dr. Zehnder is a veterinarian-scientist at the intersection of animal biology and human health. Today she joins the show to discuss her background in Cancer Biology, her specialty training in exotic/non-traditional species, and the experience of launching Fauna Bio with co-founders, Dr. Linda Goodman and Dr. Katie Grabek in 2018.

Dr. Zehnder explains how genomes from non-model systems and animals can inform our thinking about human disease, why her background in veterinary medicine gives her an advantage in studying comparative physiology, and what her team has learned about neurodegeneration from the hibernation process of the thirteen-lined ground squirrel. She talks about studying highly conserved disease traits across species and whether we can reactivate certain genetic pathways to reverse those diseases. You’ll hear about Fauna Bio’s work with RNA Seq. data, their focus on cardiovascular research and other indications they are now expanding into, as well as the company’s relationship with Novo Nordisk as they explore the connection between hibernation, metabolic changes, and obesity. Dr. Zehnder offers her perspective on the University of Washington’s Dog Aging Project, and talks about the current drug discovery pipeline at Fauna Bio. She addresses how Fauna Bio fits in with other aging research and concludes with her thoughts on how the field of comparative genomics will evolve over the next five to ten years.

Episode Highlights:

• Dr. Ashley Zehnder is a veterinarian with a background in companion exotics (birds, mammals, reptiles)
• She completed a Ph.D. in Oncology and Cancer Biology at Stanford University
• Co-founded Fauna Bio with Dr. Linda Goodman and Dr. Katie Grabek in 2018
• Her background in studying the molecular basis that drives cancer across all different species
• Studying human genetics alone became difficult and frustrating in trying to determine what drives human disease
• Turning to comparative genetics was a way to solve that problem
• Origins of Fauna Bio as a company - decided academia was not the way to take full advantage of new, richer data sets; wanted to make them usable for drug discovery and drug development as quickly as possible
• Traditional model systems organisms versus non-model systems and animals
• Model organisms do not fit the bill in trying to do therapeutics discovery for more complex disorders
• Instead of trying to mimic human diseases in model organisms, Dr. Zehnder focuses on finding similar situations that already exist and have been solved in nature, and learning from those solutions directly
• Her medical training as a veterinarian gives her an incomparable advantage in studying comparative physiology
• Scientists who focus only on humans have a blind spot to the fact that the same disease syndromes can be seen across the animal world
• Research on the thirteen-lined ground squirrel and neurodegeneration
• Certain adaptations that help animals end up causing diseases in humans; animals have a way of reversing these while humans do not
• 200 Mammals Project looks at which animals, including humans, can go into torpor
• Largely study mammalian species due to the similarities with humans
• They work with RNA-Seq data
• Studies on traumatic cardiovascular events (heart attacks) for hibernating species show that they may be resistant to damage caused by reperfusion injury 
• Fauna Bio initially focused on cardiovascular health, and is now expanding into other organs of the body, such as the brain hypothalamus, liver, kidney, muscle and skeletal tissue
• Their relationship with pharmaceutical company Novo Nordisk and studying how certain animals change their metabolism
• Brown fat versus white fat
• University of Washington’s Dog Aging Project
• Fauna Bio’s current drug discovery pipeline
• Branching out into more chronic diseases such as fibrosis
• 30 to 50% increase in life expansion for species that are able to hibernate as compared to similarly sized counterparts who do not hibernate
• What they’re learning from animals is how to repair damage in a way that reduces disease
• How the field of comparative genetics will evolve over the next five to ten years

Quotes:

“I'm a veterinarian. My background is in companion exotics. So I was clinically trained to treat birds, mammals, reptiles, all sorts of strange species. I ended up doing a Cancer Biology Ph.D. at Stanford, focused on the intersection of animal and human health.”

“Looking at cancer traits across different species, why some species get cancers, why some species don't, and understanding the molecular basis that drives all those cancers, which turns out to be the same across all these species.”

“We really have spent a lot of time trying to understand what drives human disease from a genetic level, and really became quite frustrated with the difficulty of trying to figure it out just by studying human genetics.”

“We realized that there was this huge untapped opportunity in the emerging genomic data sets for hundreds of different species that are - the genomes are coming out in higher quality RNA Seq, and Proteomics has become exponentially cheaper. So there's much richer data sets available out there for animals that have naturally evolved disease resistance.”

“It was very much aThree musketeers sort of moment, because we really needed all three of our skill sets to make what Fauna does work.”

“That's really one of the key failure points in biological development and drug development, is that transition back from animal models into humans.”

“Model organisms have a role. And if you need to knock out a gene and know what it does, I think that that's helpful. But in terms of trying to do therapeutics discovery for more complex disorders, they just don't fit the bill.”

“We do use a significant amount of human genetic data on our platform to help enrich the gene sets that we work with.”

“Let's stop trying to make these animal models mimic a human disease. And let's instead look for the reverse. Let's look for situations in nature, where there's been a solution to this problem already. And let's learn from that directly.”

“There's a complete blind spot to the fact that we see all these same disease syndromes across the animal world.”

“We're looking at disease traits and traits across species that are highly conserved. And I think that's why we've seen such success in the compounds in the genes that we've been looking at.”

“Thirteen-lined ground squirrels - they increase their metabolism by 235-fold over a matter of one or two hours. And there's just not many other models in the world that can do that repeatedly, week after week for months at a time.”

“Dogs are not necessarily a species with disease resistance, which is where we tend to focus, but a species that in many ways can age very similarly to humans - they get that same kind of cognitive disorders, they get some of the same metabolic syndromes, they can get some of the same types of muscle wasting and whatnot. But on a shorter timescale - they don't live as long. So you can do aging studies in a shorter timescale.”

“We now have seven genetic targets that we validated in human cardiac fibroblasts that can reduce collagen formation up to 60%.”

“If you look at similarly sized species - ones that hibernate and ones that don't, there is around a 30 to sometimes up to 50% lifespan extension for species that are able to hibernate.”

“That's really what we're learning from these animals is how do you repair damage in a way that reduces disease.”

“How do animals repair damage? How does that relate to lifespan extension? And how do they keep their tissues healthy even as they age? And I think that's something that we can learn from, from hibernators, and other species as well.”

“I want to be able to show that we can create drugs or help others create drugs that are going to work better than drugs that are found by traditional means.”

Links:

Email questions, comments and feedback to [email protected]

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Fauna Bio Website FaunaBio.com

Joining host Dr. Robert Hughes today on this inaugural episode of Translating Aging is our distinguished guest, Dr. Eric Verdin. Dr. Verdin is the president and CEO of the Buck Institute for Research on Aging, where his research primarily focuses on the relationship between aging and the immune system, and how immune aging is regulated by nutrition. He is also a Professor of Medicine at UCSF.

Dr. Verdin begins by sharing his medical background, including his early research on HIV transcription and what drew him to the field of aging. He discusses NAD Metabolism, its connection to the regulation of sirtuins, and his research on why NAD levels decrease during aging, which has a deleterious effect on a variety of organs. Dr. Verdin answers questions about whether NAD supplementation could be helpful in fighting aging and disease, the emergence of startup companies in the Bay Area that are attempting to address aging directly, and the challenges of conducting research on aging when it is not yet defined as a disease. He talks about establishing the world’s first Center for Female Reproductive Longevity and Equality after being approached by Nicole Shanahan (wife of Sergey Brin) about the connection between early infertility and the aging process. In addition, Dr. Verdin explains why the link between health span and life span may be more connected than we think, whether we can ever reach a life expectancy of 115 years or more in humans, and why he believes this period in time will later be viewed as the birth of a whole new age of biology and health.

To learn more about Dr. Eric Verdin, the Buck Institute, and their cutting-edge research to help people live better longer, visit BuckInstitute.org.

Episode Highlights:

• Dr. Eric Verdin’s professional background, medical education and experience
• Background in virology and evolution to field of aging
• His work studying HIV transcription led to research on biology of aging
• Most compelling questions facing aging research 
• Molecular study of aging as a field is less than 30 years old
• Number of hallmarks of aging seem to be happening independently of each other and we do not yet have a sense of the hierarchy of these hallmarks
• Chronic inflammation is a key aspect of the aging process, but was not listed in that collection of hallmarks
• Developing a better understanding of the different manifestations of aging and how they are related
• Working on one aspect of aging influences the other
• NAD Metabolism and its connection to the regulation of sirtuins 
• Decrease in NAD levels with age has deleterious consequences on a variety of organs
• Salvage pathway, CD38 Molecule, and PARP1 may play a role
• Diseases that involve chronic DNA damage and NAD depletion offer insight
• NAD supplementation to help fight against aging and disease
• NAD precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have been shown to alleviate some of the complications associated with aging in animal models 
• Questions about whether these supplements will be truly and rigorously tested to ensure efficacy
• Emergence of other startups that are focusing on aging research has created a number of amazing opportunities for translation - studying the process in humans and molecular pathways in particular
• Dr. Verdin has helped launch startup companies Napa Therapeutics and BHB Therapeutics
• Challenge that aging itself is not recognized as disease and how this impacts the ability to conduct clinical research on it
• Example of Unity Biotechnology, which targets cellular senescence
• Alternative idea is to identify a series of novel indications that are clearly linked to aging, such as Frailty and Sarcopenia
• Novartis demonstrated that pretreatment with rapamycin increased response to influenza vaccines
• Reproductive senescence, and link between early infertility and aging
• Nicole Shanahan has funded the Center for Female Reproductive Longevity and Equality at the Buck Institute for the first five years
• Goal is to increase female reproductive longevity
• Health span versus life span
• Centenarians not only live longer than most of us, but they spend less time being sick over their lifetime as well (5% versus 15%)
• Compressed morbidity and whether average life expectancy will ever reach 115 years or more
• Exciting collaborations and innovative research on the horizon for the Buck Institute

Quotes:

“I think one of the great privileges of being a basic scientist is that you can essentially study whatever you want. And I have a lot of interests and a lot of curiosity.”

“I just found it an irresistible topic to study.”

“One of the things that really drew me to the field is this realization that this is a field where fundamental questions still remain to be answered.”

“One of the things that fascinates me is really the idea of establishing clearer links between these hallmarks of aging and hopefully somewhat of a more unified theory of aging.”

“No one really believes there is a single cause of aging.”

“What is happening during aging is that NAD levels decrease, and that has been documented in a variety of organs.”

“Given the fact that NAD levels are decreasing, there’s been an interest in trying to restore these NAD levels. And one way to do this is two potential precursors to NAD: One called nicotinamide riboside (NR) and the other one called nicotinamide mononucleotide (NMN). Both of these have been explored in the literature and in humans, and both of those actually restore NAD levels to some degree.”

“These companies are just two examples of a whole ecosystem that is rapidly developing in the Bay Area.”

“The way that most companies have decided to tackle the problem is to actually use the knowledge of aging and its pathways to target really unique indications.”

“The hope is that once you have identified a drug that targets senescence, for example, in the knee, is that the same molecule could be used for further indications where senescence is also prevalent.”

“As a physician, there is a part of me that resists the idea of calling aging a disease, but clearly aging itself is a risk factor for a whole series of diseases.”

“It turns out, at least in many of the animal model systems in which we can increase life span, we also increase health span.”

“Our life span is going to continue to increase, and I think our major goal is really to make sure that these gained years actually are quality years, spent with people who are fully in command of their mental and physical abilities.”

“I’m incredibly optimistic of what we’re going to be doing in the future, but also I think we should be realistic about the difficulties that lie on this path.”

“I think it’s an incredible time to be in this field, and I suspect that when we look back 20 or 30 years from now, we will really look at his period as the birth of a whole new age of biology and health.”

Links:

Email questions, comments and feedback to [email protected]

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Description:

On Translating Aging, we talk with the worldwide community of researchers, entrepreneurs, and investors who are moving longevity science from the lab to the clinic. We bring you a commanding view of the entire field, in the words of the people and companies who are moving it forward today. The podcast is sponsored by BioAge labs, a clinical-stage biotechnology company developing therapies to extend human healthspan by targeting the molecular causes of aging.