PMC

Cells that enter the senescence program slow cell cycle progression and eventually stop proliferating. However, proliferative arrest is not associated with functional silence. Rather, senescent cells acquire the senescence-associated secretory phenotype (SASP) characterized by the secretion of proteins, such as cytokines, through which they regulate neighboring cells and tissues. SASP proteins typically elicit an inflammatory response. Cells and tissue structures potentially exposed to senescent T cells are shown.

With progressive age, the T cell compartment undergoes profound changes induced by slowing T cell replenishment, replicative stress and chronic antigen-specific and nonspecific stimulation. Three major mechanisms have been implicated in the altered T cell functionality of the elderly and of individuals affected by premature immunosenescence. Repertoire contraction results from uneven clonal expansion and restricts T cell diversity. Recently, several molecular networks have been discovered which rewire the signaling apparatus of senescent T cells, leading to inappropriate responsiveness. Inefficiencies in DNA repair have a major impact on T cell survival, and possibly T cell differentiation, as they lower the apoptotic threshold and impose chronic genomic stress.