Long-term culture studies using CD8 T cells, the immune cells responsible for control of viral infection, have identified the major features of replicative senescence. Aging is associated with increased proportions of CD8 T cells with similar characteristics, such as absence of expression of the CD28 costimulatory molecule and reduced antiviral effector functions. Proinflammatory cytokines produced by senescent CD8 T cells also may exert pleiotropic suppressive effects on overall immune function and bone homeostasis. Thus, modulation of T cell replicative senescence may provide a comprehensive therapeutic strategy to prevent multiple age-associated pathologies.