Mild stress-induced stimulation of heat-shock protein synthesis and improved functional ability of human fibroblasts undergoing aging in vitro.

Repeated mild heat-shock (RMHS) treatment has anti-aging hormetic effects on human fibroblasts undergoing aging in vitro. Since heat and various other stresses induce the transcription and translation of heat-shock proteins (Hsp), it was investigated if RMHS treatment affected the basal levels of four major stress proteins Hsp27, 70, 90 and Hsc70. The basal levels of Hsp27, Hsc70, and Hsp70 increased significantly in late passage senescent cells, which is indicative of an adaptive response to cumulative intracellular stress during aging. RMHS increased the levels of these Hsp even in early passage young cells and were maintained high throughout their replicative lifespan. In comparison, the amount of Hsp90 decreased both with aging and RMHS treatment in vitro. However, whereas the difference in the levels of Hsp70 and Hsp90 was statistically significant, the levels of Hsp27 and Hsc70 were statistically similar in normal and RMHS-treated serially passaged cells. These alterations were accompanied by an improved functional and survival ability of the cells in terms of increased proteasomal activities, increased ability to decompose H(2)O(2), reduced accumulation of lipofuscin and enhanced resistance to ethanol, H(2)O(2) and UV-A radiation.