MAP Kinases and Heat Shock–Induced Hormesis in Human Fibroblasts during

ABSTRACT: Adult human skin fibroblasts were exposed repeatedly to 41◦C or 42◦C heat shock (HS) for 1 h twice a week during serial passaging throughout their replicative life span. On the basis of longevity curves, cell size, and morphology, we observed that repeated mild heat shock (RMHS) at 41,◦C had strong anti-aging hormetic effects, including 20% extension of cellular longevity. The basal levels of the MAP kinases JNK1, JNK2, and p38 increased during serial passaging, while that of ERK2 decreased. RMHS further exaggerated these effects, which suggests that age-related changes in MAP kinases may be an adaptive response for better cell survival