•Impaired immunological responsiveness is common in the elderly
•The immunological competence of an individual is determined by the presence of mature lymphocytes formed in primary lymphoid organs, and secondary lymphoid tissues such as the liver, lung and GI tract.
•Immunological equilibrium requires steady lymphocyte output, and controlled expansion
•Thymic and lymph-node stromal microenvironments thus represent key elements in the development of the adaptive immune system. Consequently, impairment of the lymphoid microenvironment will ultimately lead to insufficient primary and secondary immune responses or to the decline of thymic selection, manifesting in immune senescence accompanied by late-onset autoimmune disorders, often observed in elderly.
•Self-tolerant cytotoxic and helper T-lymphocytes, the crucial regulator cells in adaptive immune responses, develop in the specialized epithelial network of the thymus. The thymus, however, gradually loses its capacity to support lymphopoiesis in an involution process that results in a decline of de novo T-cell production.
•Cancers of epithelial origin (carcinomas) are the most frequent type of malignancy in humans, with their incidence and aggressiveness increasing with age
•This observation raises the question as to whether the aging process itself contributes to tumor progression
•. In this regard, telomere biology seems to play a pivotal role since shortening of telomeres has been associated with cellular senescence and organismal aging as well as with cancer incidence and mortality .
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•In the multistep carcinogenesis model, telomere shortening has been observed together with increased chromosome instability (CIN) in early precancerous conditions
•Experimental models have also shown that a transient period of telomere instability followed by reactivation of telomerase contributes to the acquisition of the metastatic phenotype