THE EXPRESSION OF HEAT-SHOCK-PROTEIN-70 DECREASES WITH CELLULAR SENESCENCE IN-VITRO AND IN CELLS DERIVED FROM YOUNG AND OLD HUMAN-SUBJECTS

Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of stresses, it wa s of interest to determine what effect cellular senescence in vitro an d cells cultured in vitro from young and old human donors have on the ability of cells to regulate the expression of heat shock protein 70 ( hsp70), the most prominent and most evolutionary conserved of the heat shock proteins. The ability of early and late passage IMR-90 lung fib roblasts and epidermal melanocytes and skin fibroblasts obtained from young and old human donors to express hsp70 was determined after a bri ef heat shock. We found that the levels of hsp70 protein and mRNA were lower in late passage cells and cells from old donors than in early p assage cells and cells from young donors. The binding activity of the heat shock transcription factor HSF1, as measured by a gel shift assay , was significantly higher in early passage cells and cells from young donors in comparison to late passage cells and cells from old donors. In addition, the levels of HSF1 decreased significantly in late passa ge cells and cells from old donors in comparison to early passage cell s and cells from young donors. Thus, our study demonstrates that the i nduction of hsp70 by hyperthermia in fibroblasts is significantly lowe r in late passage fibroblasts and in fibroblasts from old donors. In a ddition, our study shows that the decline in hsp70 expression during c ellular senescence in vitro and in cells derived from old human subjec ts is paralleled by a decrease in the levels of HSF1. (C) 1998 Academi c Press.