Journal Club: Slaying the Sleeper Cells of Aging

Today we are revisiting a topic and episode that was originally aired back when Journal Club was part of the a16z podcast. We are covering it again in light of a new research article published in Science, as both this episode and this newer research article are trying to find a way to kill senescent cells.

The article we discuss in this episode, "Senolytic CAR T cells reverse senescence-associated pathologies" by Amor et al, published in Nature, selectively targets senescent cells with engineered T cells.

The new article, "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders" by Johmura et al, published in Science, kills senescent cells by inhibiting an enzyme essential for their metabolism.

So what are senescent cells, and why is killing them so important? Senescent cells are those in a non-dividing but metabolically active state, and what’s interesting is that they play both protective and pathological roles in the body. When senescent cells accumulate, as often happens during aging, they kick off an inflammatory process that underlies many age-related diseases. Thus the targeted destruction of senescent cells has the potential to treat a wide range of conditions, and possibly to improve longevity.

Both of the approaches described in these two articles have their pros and cons, and it remains to be seen which will be effective in humans, but together they highlight the interest and importance of senescence-killing, or senolytic, methods for future therapeutics.

On this episode, a16z general partner Jorge Conde (@JorgeCondeBio) and bio deal team partner Andy Tran (@andy23tran) join host Lauren Richardson (@lr_bio) to discuss the results and implications of the article "Senolytic CAR T cells reverse senescence-associated pathologies" by Corina Amor, Judith Feucht, Josef Leibold, Yu-Jui Ho, Changyu Zhu, Direna Alonso-Curbelo, Jorge Mansilla-Soto, Jacob A. Boyer, Xiang Li, Theodoros Giavridis, Amanda Kulick, Shauna Houlihan, Ellinor Peerschke, Scott L. Friedman, Vladimir Ponomarev, Alessandra Piersigilli, Michel Sadelain & Scott W. Lowe, published in Nature.

The introduction also references the article "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders" by Yoshikazu Johmura, Takehiro Yamanaka, Satotaka Omori, Teh-Wei Wang, Yuki Sugiura, Masaki Matsumoto, Narumi Suzuki, Soichiro Kumamoto, Kiyoshi Yamaguchi, Seira Hatakeyama, Tomoyo Takami, Rui Yamaguchi, Eigo Shimizu, Kazutaka Ikeda, Nobuyuki Okahashi, Ryuta Mikawa, Makoto Suematsu, Makoto Arita, Masataka Sugimoto, Keiichi I. Nakayama, Yoichi Furukawa, Seiya Imoto, Makoto Nakanishi