Hormetic prevention of molecular damage during cellular aging of human skin fibroblasts and keratinocytes.

Progressive accumulation of molecular damage is a hallmark of cellular aging, which is amenable to intervention and prevention by hormesis through mild stress. Our studies have shown that repeated mild heat stress (RMHS) has antiaging effects on growth and various other cellular and biochemical characteristics of normal human skin fibroblasts undergoing aging in vitro. RMHS at 41 degrees C, for 1 h twice a week, increased the basal levels of various chaperones, reduced the accumulation of oxidatively and glycoxidatively damaged proteins, stimulated proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogen peroxide, and UV-B rays, enhanced the levels of various antioxidant enzymes, and increased the phosphorylation-mediated activities of various stress kinases. RMHS-exposed human fibroblasts are also better protected against glucose- and glyoxal-induced growth inhibition and apoptosis. We have also observed various hormetic effects of RMHS on normal human epidermal keratinocytes, which include increased replicative life span, increased proteasomal activity, and enhanced levels of Na/K-ATPase pump. We are also testing the above effects of RMHS in combination with potential hormetic molecules, such as curcumin, on aging, longevity, and differentiation of human cells in culture.