Apoptosis in stress-induced and spontaneously senescent human fibroblasts.

Although apoptosis has been shown in vivo to be involved in the aging process, in vitro studies of age-dependent apoptosis are limited. In this study, apoptosis was examined in normal human fibroblasts exposed to H(2)O(2) to induce premature senescence and in spontaneously senescent human fibroblasts. Although apoptosis was not observed for several days after exposure to H(2)O(2), morphological changes indicating apoptosis were evident in about 5% of cells 7 days after exposure to 80microM H(2)O(2), concomitantly with expression of senescent phenotype. The apoptotic changes were preceded by caspase activation in majority of the exposed cells. As well as H(2)O(2)-induced senescent cells, spontaneously senescent human fibroblasts showed apoptotic changes in about 2% of cells and majority of the senescent cells also showed activation of caspases. The results indicate that the apoptosis pathway is activated in H(2)O(2)-induced and spontaneously senescent human fibroblasts in vitro.