Heat shock response, heat shock transcription factor and cell aging.
A characteristic feature of aging is a progressive impairment in the ability to adapt to environmental challenges. The purpose of this article is to review the evidence of an attenuated response to heat and physiological stresses in a number of mammalian aging model systems, including the human diploid fibroblasts in culture, whole animals and animal-derived cells and cell cultures, as well as peripheral blood mononuclear cells obtained from human donors. Analyses of the regulation and function of heat shock factor 1 (HSF1), a transcription factor that mediates the response to heat shock, showed that while the relative abundance of both the hsf1 transcript and the HSF1 protein did not change as a function of age, the responsiveness of HSF1 to heat-induced activation, as measured by its trimerization and ability to bind to the heat shock element consensus sequence, was inversely related to the age of the cells used. Given the fundamentally important role of heat shock proteins (HSPs) in many aspects of protein homeostasis and signal transduction it seems likely that the inability, or compromised ability, of aging cells and organisms to activate HSF1 and produce HSPs in response to stress would contribute to the well-known increase in morbidity and mortality of the aged when challenged.
Lee
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YK
Department of Biological Sciences, Rutgers-The State University of New Jersey, Piscataway 08855-1059, USA.
Manalo
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Liu
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D000375:Aging / Q000502:physiology*; D016922:Cellular Senescence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D012769:Shock / Q000235:genetics* / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors