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 stress such as heat is universal to all organisms and is believed to play a critical protective role. Therefore, it was of interest to determine the influence of aging on the ability of lymphocytes to express the 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 showed a marked decrease in the induction of hsp70 protein levels or hsp70 synthesis when compared to lymphocytes isolated from young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys. The decline with age in the induction of hsp70 by lymphocytes from rats was paralleled by a decrease in the induction of hsp70 mRNA and the nuclear transcription of hsp70. In addition, it was found that the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be physiologically important because the viability of spleen lymphocytes exposed to high temperatures decreases significantly with age.
Pahlavani
M A
MA
Geriatric Research, Education and Clinical Center, Audie L. Murphy Memorial Veterans Hospital, University of Texas Health Science Center, San Antonio 78284, USA.
Harris
M D
MD
Moore
S A
SA
Weindruch
R
R
Richardson
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors