THE EXPRESSION OF HEAT-SHOCK PROTEIN-70 DECREASES WITH AGE IN LYMPHOCYTES FROM RATS AND RHESUS-MONKEYS

The ability of cells to express heat shock proteins in response to a s tress such as heat is universal to all organisms and is believed to pl ay a critical protective role. Therefore, it was of interest to determ ine the influence of aging on the ability of lymphocytes to express th e heat shock protein hsp70 in response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated from old (24-26 months) rats s howed a marked decrease in the induction of hsp70 protein levels or hs p70 synthesis when compared to lymphocytes isolated from young (4-5 mo nths) rats. An age-related decrease in the induction of hsp70 levels b y heat also was observed in peripheral lymphocytes isolated from rhesu s monkeys, The decline with age in the induction of hsp70 by lymphocyt es from rats was paralleled by a decrease in the induction of hsp70 mR NA and the nuclear transcription of hsp70. In addition, it was found t hat the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefo re, it appears that the reduced ability of lymphocytes from old rats t o express hsp70 in response to a heat shock occurs at the level of tra nscription because of an alteration in the ability of the heat shock t ranscription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be phys iologically important because the viability of spleen lymphocytes expo sed to high temperatures decreases significantly with age. (C) 1995 Ac ademic Press, Inc.