THE ACCUMULATION OF NONREPLICATIVE, NONFUNCTIONAL, SENESCENT T-CELLS WITH AGE IS AVOIDED IN CALORICALLY RESTRICTED MICE BY AN ENHANCEMENT OF T-CELL APOPTOSIS

Peripheral blood lymphocytes of elderly humans show an increased perce ntage of T cells with characteristics of replicative senescence. Simil arly, the overall decrease in T cell proliferation in aged mice reflec ts a progressively increasing proportion of non-functional cells rathe r than a uniform decline in function by all cells. The improved immune function of calorically restricted (CR) animals is, paradoxically, ac companied by a relative lymphopenia. To test whether the reduction in lymphocyte number in the CR mice might reflect more efficient eliminat ion of T cells, we measured apoptosis in young, old and CR old mice. T cell apoptosis induced by irradiation, Staurosporine, anti-CD3, and h eat shock was reduced by 62, 42, 32, and 30%, respectively, in old com pared with young mice. Caloric restriction normalized apoptosis in T c ells from aged mice. Enhanced elimination of non-functional T cells in CR mice may be, at least in part, responsible for their improved immu ne functional status relative to non-CR mice of the same age. (C) 1997 Elsevier Science Ireland Ltd.