[The aged and stress response].
It is generally considered that aged people have less potential for adapting to environmental changes. In this review, an attempt is made to see whether experimental results support the above working hypothesis and how lower adaptation potential is involved in the aging process. Studies with human beings, rats and human diploid fibroblasts showed a gradual reduction of heat shock proteins (HSPs) and their mRNA and DNA binding activity of heat shock factor (HSF) during aging. Furthermore, the activation of HSF from monomer to trimer was reduced irrespective of the presence of comparative amounts of HSF in the aged cells. Cells from elder organisms or late-staged fibroblasts in culture may have altered the redox state and/or abnormal proteins. A clear interpretation of how these changes influence the activation of HSF in aged cells is impossible at present. Stress kinase JNK (Jun NH2kinase) promotes the signal transduction pathway of apoptosis. In contrast, overexpression of HSP suppresses apoptosis mediated by JNK, resulting in the increase of carcinogenic risk of aged cells. HSP as chaperone maintains unfolded intermediate protein to protect aggregation or to form native conformation of nascent protein. On the contrary, this intermediate (rich in beta-sheet) with aid from such as apoprotein E can make insoluble amyloid fibers in the brain of aged people. In certain cases, overexpression of HSP is rather toxic to the cells.
Higashi
K
K
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
D000222:Adaptation, Physiological / Q000502:physiology*; D000368:Aged / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D018384:Oxidative Stress; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*
D018840:HSP70 Heat-Shock Proteins