Aging reduces adaptive capacity and stress protein expression in the liver after heat stress.

A decline in an organism's ability to cope with stress through acute response protein expression may contribute to stress intolerance with aging. We investigated the influence of aging on stress tolerance and the capacity to synthesize the 70-kDa heat shock protein (HSP70) in young and old rats exposed to an environmental heating protocol. Livers were assessed for injury and HSP70 expression after heat stress by use of immunohistochemical and immunoblotting techniques. The inducible HSP70 response in the cytoplasm and nucleus was markedly reduced with age at several time points over a 48-h recovery period, although senescent rats were able to strongly express HSP70 early in recovery. Older animals had extensive zone-specific liver injury, which corresponded to the diminished HSP70 response observed in these regions, and a significant reduction in thermotolerance compared with their young counterparts. These data highlight the regional nature of stress-induced injury and HSP70 expression in the liver and the impact of aging on these responses. Furthermore, the results suggest a functional link between the age-related decrements in the expression of inducible HSP70 and the pathophysiological responses to heat stress.

[1]  R. Bucala,et al.  Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[2]  K. Abe,et al.  Different thresholds of HSP70 and HSC70 heat shock mRNA induction in post-ischemic gerbil brain , 1992, Brain Research.

[3]  L. Oberley,et al.  Immunohistochemical localization of glutathione-S-transferase and glutathione peroxidase in adult Syrian hamster tissues and during kidney development. , 1991, The American journal of pathology.

[4]  U. K. Laemmli,et al.  Cleavage of structural proteins during , 1970 .

[5]  P. Moseley,et al.  New Frontiers in Thermoregulation and Exercise , 1993, Sports medicine.

[6]  S. Al-Sedairy,et al.  Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. , 1991, Journal of applied physiology.

[7]  M. Jäättelä,et al.  Heat-shock proteins protect cells from monocyte cytotoxicity: possible mechanism of self-protection , 1993, The Journal of experimental medicine.

[8]  A. Henschel,et al.  An analysis of the heat deaths in St. Louis during July, 1966. , 1969, American journal of public health and the nation's health.

[9]  D. Yellon,et al.  Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. , 1995, The Journal of clinical investigation.

[10]  J. Fargnoli,et al.  Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Brenner,et al.  A simplified method for the preparation of transcriptionally active liver nuclear extracts. , 1990, DNA and cell biology.

[12]  B. Li,et al.  Attenuated induction of heat shock gene expression in aging diploid fibroblasts. , 1989, The Journal of biological chemistry.

[13]  K. Riabowol,et al.  Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. , 1988, Science.

[14]  B. Wu,et al.  The effect of age on the synthesis of two heat shock proteins in the hsp70 family. , 1993, Journal of gerontology.

[15]  R. Currie,et al.  Characterization of the synthesis and accumulation of a 71-kilodalton protein induced in rat tissues after hyperthermia. , 1983, Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire.

[16]  C. Tipton,et al.  Thermal adjustments to nonexertional heat stress in mature and senescent Fischer 344 rats. , 1990, Journal of applied physiology.

[17]  J. Fargnoli,et al.  Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats. , 1991, The American journal of physiology.

[18]  C. Franceschi,et al.  Mitochondria are selective targets for the protective effects of heat shock against oxidative injury. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. Melcher,et al.  Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. , 1999, Journal of immunology.

[20]  B. Fleischer,et al.  In vivo and in vitro activation of T cells after administration of Ag-negative heat shock proteins. , 1999, Journal of immunology.

[21]  R. Weindruch,et al.  Caloric restriction improves thermotolerance and reduces hyperthermia‐induced cellular damage in old rats , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  V. Guerriero,et al.  HSP70 induction during exercise and heat stress in rats: role of internal temperature , 1995 .

[23]  W. Welch Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. , 1992, Physiological reviews.

[24]  G. Li,et al.  Elevated levels of 70,000 dalton heat shock protein in transiently thermotolerant Chinese hamster fibroblasts and in their stable heat resistant variants. , 1985, International journal of radiation oncology, biology, physics.

[25]  R. Johnston,et al.  Competitive inhibition of hsp70 gene expression causes thermosensitivity. , 1988, Science.

[26]  H. Howe,et al.  Heat-related deaths during the July 1995 heat wave in Chicago. , 1996, The New England journal of medicine.

[27]  P. Moseley,et al.  HSP70 accumulation in tissues of heat-stressed rats is blunted with advancing age. , 1995, Journal of applied physiology.

[28]  H. Kolb,et al.  Human 60-kDa heat-shock protein: a danger signal to the innate immune system. , 1999, Journal of immunology.

[29]  J. Raese,et al.  Expression of Heat Shock Protein 70 and Heat Shock Cognate 70 Messenger RNAs in Rat Cortex and Cerebellum After Heat Shock or Amphetamine Treatment , 1991, Journal of neurochemistry.

[30]  P. Gathiram,et al.  Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates. , 1988, Circulatory shock.

[31]  P. Moseley,et al.  Differential effects of exercise and heat stress on liver HSP70 accumulation with aging. , 1996, Journal of applied physiology.

[32]  A. Ryan,et al.  Tissue-specific HSP70 response in animals undergoing heat stress. , 1995, The American journal of physiology.

[33]  M. Kew,et al.  Liver damage in heatstroke. , 1970, The American journal of medicine.