Senescent T Cells And Mortality

The ultimate effect of T cells on aging is with respect to mortality itself. Early work suggested a connection, based on correlative data, between T cell proliferative responses in cell culture and mortality over the subsequent few years (Wikby et al., 1998). More recently, telomere analysis of total lymphocytes in a group of 60 year olds was shown to be predictive of mortality many years later (Cawthon et al., 2003). In these studies, it was shown that the individuals who had telomeres in the lowest quartile were 7-8 times more likely to die from infections compared with those with the longest telomeres. Longitudinal studies of elderly Swedes over several decades confirm the link between immune parameters and lifespan. These data show that early mortality is associated with a so-called immune risk phenotype, which includes a cluster of T cell parameters, including high proportions of senescent CD8+ T cells (Nilsson et al., 2003). Interestingly, the presence of these risk factors is strongly correlated with chronic CMV infection (Wikby et al., 2002). Moreover, the predictive value of the immune profile is retained for a variety of causes of death. In sum, there is accumulating evidence that immune system function is intimately linked with a variety of age-related pathologies, some of which are actual causes of death.

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