Attenuated heat shock transcriptional response in aging: molecular mechanism and implication in the biology of aging

A characteristic feature of aging is a progressive impairment in the ability to adapt to environmental challenges. The purpose of this review is to present the experimental evidence of an attenuated heat shock transcriptional response to heat and physiological stresses in a number of aging mammalian model systems. These include 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. The possibility that age-dependent changes in cellular redox status, as exemplified by the increased production of reactive oxygen inter-mediates and accumulation of oxidatively-modified proteins, affects the regulation and function of the heat shock factor 1 (HSF1) and contributes to the attenuated heat shock transcriptional response in aging cells and organisms is discussed. Given the fundamentally important role of 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 produce HSPs in response to stress would contribute to the well known increase in morbidity and mortality of the aged when challenged.