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Glucocorticoids and aging

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Abstract

Information on the role of glucocorticoids in the aging of vertebrate species is reviewed. There is strong evidence that elevated plasma glucocorticoid levels have a causal role in the rapid deterioration following reproduction in semelparous vertebrate species. If this deterioration is an example of rapid senescence, then it is clear that glucocorticoids can promote aging processes in vertebrate species. However, the evidence that glucocorticoids promote aging in the gradual senescence characteristic of most vertebrate species is not robust. Indeed, there is reason to believe that periods of moderately elevated plasma glucocorticoid levels may retard aging processes in rats, mice, and humans.

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References

  1. Selye H.: A syndrome produced by diverse nocuous agents. Nature 138: 32–34, 1936.

    Article  Google Scholar 

  2. Masoro E.J.: Aging: Current concepts. In: Masoro E.J. (Ed.), Handbook of Physiology, Section 11: Aging. Oxford University Press, New York, 1995, pp. 3–21.

    Google Scholar 

  3. Riegle G.D.: Aging and adrenocortical function. In: Everitt A.W., Burgess J.A. (Eds.), Hypothalamus, Pituitary, and Aging. Charles C. Thomas, Springfield, IL, 1976, pp. 547–552.

    Google Scholar 

  4. Finch C.E.: Longevity, Senescence and the Genome. University of Chicago Press, Chicago, IL, 1990.

    Google Scholar 

  5. Sapolsky R.M.: The adrenalcortical axis. In: Schneider E.L., Rowe J.W. (Eds.), Handbook of the Biology of Aging. Academic Press, San Diego, CA, 1990, pp. 330–346.

    Chapter  Google Scholar 

  6. Lee A.K., Cockburn A.: Spring decline in small mammalian populations. Acta Zool. Fennica 173: 75–76, 1985.

    Google Scholar 

  7. Finch C.E., Rose M.R.: Hormones and the physiological architecture of life history evolution. Quant. Rev. Biol. 70: 1–52, 1995.

    Article  CAS  Google Scholar 

  8. Hane S., Robertson O.H.: Changes in plasma concentration of 17-hydroxycorticosteroids accompanying sexual maturation and spawning of the Pacific salmon (Oncorhynchus tshawytscha) and rainbow trout (Salmo gairdnerii). Proc. Natl. Acad. Sci. USA 45: 886–893, 1959.

    Article  PubMed  CAS  Google Scholar 

  9. vanOverbecke A.P., McBride J.R.: Histological effects of 11-ketotestosterone, 17α-methyltestosterone, estradiol cyprionate, and cortisol on the interrenal tissue, thyroid gland, and pituitary gland of gonadectomized Sockeye salmon (Oncorhynchus nerka). J. Can. Res. Bd. Can. 28: 477–481, 1971.

    Article  Google Scholar 

  10. Robertson O.H., Hane S., Wexler B.C., Rinfret A.P.: The effect of hydrocortisone on immature rainbow trout (Salmo gairdnerii). Gen. Comp. Endocrinol. 3: 422–436, 1963.

    Article  CAS  Google Scholar 

  11. Robertson O.H., Wexler B.C., Miller B.F.: Degenerative changes in the cardiovascular system of spawning Pacific salmon (Oncorhynchus tshawytscha). Circ. Res. 9: 826–834, 1961.

    Article  PubMed  CAS  Google Scholar 

  12. Larsen L.O.: The role of hormones in reproduction and death in lampreys and other species which reproduce once and die. In: Lofts B., Holmes W.N. (Eds.), Current Trends in Comparative Endocrinology. Hong Kong University Press, Hong Kong, 1985, pp. 613–616.

    Google Scholar 

  13. Dickhoff W.W.: Salmonoids and annual fishes: Death after sex. In: Schreibman M.P., Scanes C.G. (Eds.), Development, Maturation, and Senescence of Neuroendocrine Systems: A Comparative Approach. Academic Press, New York, 1989, pp. 256–266.

    Google Scholar 

  14. Kirkwood T.B.L., Cremer T.: Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress. Hum. Genet. 60: 101–121, 1982.

    Article  PubMed  CAS  Google Scholar 

  15. Weindruch R.: Animal models. In: Masoro E.J. (Ed.), Handbook of Physiology, Section 11: Aging. Oxford University Press, New York, 1995, pp. 37–52.

    Google Scholar 

  16. Sapolsky R.M.: Do glucocorticoid concentrations rise with age in the rat? Neurobiol. Aging 13: 171–174, 1992.

    Article  PubMed  CAS  Google Scholar 

  17. DeKoskey S.T., Scheff S.W., Cotman C.W.: Elevated corti-costerone levels. A possible cause for reduced axon sprouting in aged animals. Neuroendocrinology 38: 33–38, 1984.

    Article  Google Scholar 

  18. Meany M.J., Aitken D.H., Van Kerkel C., Bhatnager S., Sapolsky R.M.: Effect of neonatal handling on age-related impairments associated with the hippocampus. Science 239: 766–768, 1988.

    Article  Google Scholar 

  19. Sapolsky R.M., Krey L.C., McEwen B.S.: The adrenocortical stress-response in the aged male rat: Impairment of recovery from stress. Exp. Gerontol. 18: 55–64, 1983.

    Article  PubMed  CAS  Google Scholar 

  20. Stewart J., Meany M.J., Aitken D., Jensen L., Kalant N.: The effect of acute life-long food restriction on basal and stress-induced serum corticosterone level in young and aged rats. Endocrinology 123: 1934–1941, 1988.

    Article  PubMed  CAS  Google Scholar 

  21. Sabatino F., Masoro E.J., McMahan C.A., Kuhn R.W.: Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. J. Gerontol. 46: B171–B179, 1991.

    Article  PubMed  CAS  Google Scholar 

  22. Hess G., Riegle G.: Adrenocortical responsiveness to stress and ACTH in aging rats. J. Gerontol. 25: 354–358, 1970.

    Article  PubMed  CAS  Google Scholar 

  23. Sonntag W.E., Golizek A.G., Brodish A., Eldridge J.C.: Diminished diurnal secretion of adrenocorticotropin (ACTH) but not corticosterone in old rats: Possible relation to increased adrenal sensitivity to ACTH in vivo. Endocrinology 120: 2308–2315, 1987.

    Article  PubMed  CAS  Google Scholar 

  24. Tang F., Phillips J.G.: Some age-related changes in pituitary-adrenal function in the male laboratory rat. J. Gerontol. 33: 377–382, 1978.

    PubMed  CAS  Google Scholar 

  25. Ida Y., Tanaka M., Tsuda A.: Recovery of stress-induced increase in noradrenaline turnover is delayed in specific brain regions of old rats. Life Sci. 34: 2357–2361, 1984.

    Article  PubMed  CAS  Google Scholar 

  26. Brodish A., Odio M.: Age-dependent effects of chronic stress on ACTH and corticosterone responses to acute novel stress. Neuroendocrinology 49: 496–501, 1989.

    Article  PubMed  CAS  Google Scholar 

  27. Meany M., Aitken D., Sapolsky R.: Postnatal handling attenuates neuroendocrine, anatomical, and cognitive dysfunctions associated with aging in female rats. Neurobiol. Aging 12: 31–42, 1990.

    Article  Google Scholar 

  28. Oxenkrug G.F., McIntyre I.M., Stanley M., Gershon S.: Dexamethasone suppression test: experimental model in rats and effect of age. Biol. Psychiatry 19: 413–416, 1984.

    PubMed  CAS  Google Scholar 

  29. Sapolsky R.M., Krey L.C., McEwen B.S.: The adrenocortical axis in the aged rat: Impaired sensitivity to both fast and delayed feedback inhibition. Neurobiol. Aging 7: 331–335, 1986.

    Article  PubMed  CAS  Google Scholar 

  30. Sapolsky R.M., Krey L.C., McEwen B.S.: The neuroen-docrinology of stress and aging: The Glucocorticoid Cascade Hypothesis. Endocr. Rev. 7: 284–301, 1986.

    Article  PubMed  CAS  Google Scholar 

  31. Stein-Behrens B.A., Sapolsky R.M.: Stress, glucocorticoids, and aging. Aging Clin. Exp. Res. 4: 197–210, 1992.

    Article  CAS  Google Scholar 

  32. Sapolsky R.M., Donnelly T.: Vulnerability to stress-induced tumor growth increases with age in the rat: Role of glucocorticoid hypersecretion. Endocrinology 117: 662–666, 1985.

    Article  PubMed  CAS  Google Scholar 

  33. Landfield P.W., Eldridge J.C.: The glucocorticoid hypothesis of brain aging and neurodegeneration: Recent modifications. Acta Endocrinol. (Copenh.) 125: 54–64, 1991.

    CAS  Google Scholar 

  34. Landfield P.W., Waymire J.L., Lynch G.S.: Hippocampal aging and adrenocorticoids: quantitative correlations. Science 202: 1098–1102, 1978.

    Article  PubMed  CAS  Google Scholar 

  35. Landfield P.W., Baskin R.K., Pitler T.A.: Brain aging correlates. Retardation by hormonal-pharmacological treatments. Science 214: 581–584, 1981.

    Article  PubMed  CAS  Google Scholar 

  36. Kerr D.S., Campbell L.W., Applegate M.D., Brodish A., Landfield P.W.: Chronic stress-induced acceleration of electrophysiological and morphological biomarkers of aging. J. Neurosci. 11: 1316–1324, 1991.

    PubMed  CAS  Google Scholar 

  37. Issa A.M., Rowe W., Gauthier S., Meany M.J.: Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. J. Neurosci. 10: 3247–3254, 1990.

    PubMed  CAS  Google Scholar 

  38. Masoro E.J.: Dietary restriction and aging. J. Am. Geriatr. Soc. 41: 994–999, 1993.

    PubMed  CAS  Google Scholar 

  39. Masoro E.J.: Retardation of aging processes by nutritional means. Ann. NY Acad. Sci. 673: 29–35, 1992.

    Article  PubMed  CAS  Google Scholar 

  40. Nelson J.F.: The potential role of endocrine systems in the retardation of aging by caloric restriction. Age Nutr. 3: 171–178, 1992.

    Google Scholar 

  41. Klebanov S., Diais W., Stavinoha W., Suh Y., Nelson J.F.: Hyperadrenocorticism, attenuated inflammation and the life-prolonging action of food restriction in mice. J. Gerontol. 50A: B78–B82, 1995.

    Article  CAS  Google Scholar 

  42. Spencer R.L., Miller A.H., Stein M., McEwen B.S.: Corticosterone regulation of Type I and Type II adrenal steroid receptors in brain, pituitary, and immune tissue. Brain Res. 549: 236–246, 1991.

    Article  PubMed  CAS  Google Scholar 

  43. Han E., Levin N., Bengami B., Roberts J.L., Suh H., Karelus K., Nelson J.F.: Hyperadrenocorticism and food restriction-induced life extension in the rat: evidence for divergent regulation of pituitary proopiomelanocortin-RNA and adrenocorticotropic hormone biosynthesis. J. Gerontol. 50A: B288–B294, 1995.

    Article  CAS  Google Scholar 

  44. Nelson J.F., Levin N., Karelus K., Roberts J., Brooks B.: Effects of aging and food restriction on hypothalamic neuropeptide Y (NPY) and corticotropin releasing hormone (CRH) mRNA’s in Fischer 344 rats. Soc. Neurosci. Absts. 19: 897, 1993.

    Google Scholar 

  45. Nelson J.F.: Calorie restriction as a probe for understanding neuroendocrine involvement in aging processes. Neuroprotocols: A Companion to Methods in Neurosciences 4: 204–209, 1994.

    Article  Google Scholar 

  46. Munck A., Guyre P.M., Holbrook N.J.: Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr. Rev. 5: 25–44, 1984.

    Article  PubMed  CAS  Google Scholar 

  47. Masoro E.J.: Diet and the aging processes. Clin. J. Sport Med. 4: 262–267, 1994.

    Article  Google Scholar 

  48. Nelson J.F.: The potential role of selected endocrine systems in aging processes. In: Masoro E.J. (Ed.), Handbook of Physiology, Section 11: Aging. Oxford University Press, New York, 1995, pp. 377–394.

    Google Scholar 

  49. Heydari A.R., Wu B., Takahashi R., Richardson A.: The expression of heat shock protein 70 is altered by age and diet at the level of transcription. Mol. Cell. Biol. 13: 2909–2918, 1993.

    PubMed  CAS  Google Scholar 

  50. Bellamy D.: Long-term action of prednisolone phosphate on a strain of short lived mice. Exp. Gerontol. 3: 327–333, 1968.

    Article  PubMed  CAS  Google Scholar 

  51. Forbes W.F.: The effect of prednisolone phosphate on life span of DBA/6J mice. Exp. Gerontol. 10: 27–29, 1975.

    Article  PubMed  CAS  Google Scholar 

  52. Hochschild R.: Effects of various drugs on longevity in female C57BL/6J mice. Gerontologia 19: 271–280, 1973.

    Article  PubMed  CAS  Google Scholar 

  53. Sacher G.A.: Life table modification and life prolongation. In: Finch C.E., Hayflick L. (Eds.), Handbook of the Biology of Aging. Van Nostrand Reinhold, New York, 1977, pp. 582–638.

    Google Scholar 

  54. Holloszy J.O., Smith E.K.: Longevity of cold-exposed rats: A reevaluation of the “rate of living theory”. J. Appl. Physiol. 61: 1656–1660, 1986.

    PubMed  CAS  Google Scholar 

  55. Pashko L.L., Schwartz A.G.: Reversal of food restriction-induced inhibition of mouse skin tumor promotion by adrenalectomy. Carcinogenesis 10: 1925–1928, 1992.

    Article  Google Scholar 

  56. Miller R.A.: Gerontology as oncology. Research on aging as the key to the understanding of cancer. Cancer 68: 2496–2501, 1991.

    Article  PubMed  CAS  Google Scholar 

  57. Weindruch R., Walford R.: The Retardation of Aging and Disease by Dietary Restriction. Charles C. Thomas, Springfield, IL, 1988.

    Google Scholar 

  58. Schwarz J.A., Viaje A., Slaga T.J., Yuspa S.H., Hennings H., Lichti U.: Fluocinolone acetonide: A potent inhibitor of mouse skin tumor promotion and epidermal DNA synthesis. Chem. Biol. Interactions 17: 331–347, 1977.

    Article  CAS  Google Scholar 

  59. Schwartz A.G., Pashko L.L.: Role of adrenocortical steroids in mediating cancer-preventive and age-retarding effects of food restriction in laboratory rodents. J. Gerontol. 49: B37–B41, 1994.

    Article  PubMed  CAS  Google Scholar 

  60. O’Steen W.K., Cadwallader L.B., Vinsant S., Landfield P.W.: Biomarkers of hippocampal and retinal aging are not altered by dietary restriction. Soc. Neurosci. Absts. 16: 1161, 1990.

    Google Scholar 

  61. Armani D., Karbowiak I., Scali M., Orlandini E., Zampollo V., Vittadello G.: Corticoid receptors and lymphocyte subsets in mononuclear leukocytes in aging. Am. J. Physiol. 262: E464–E466, 1992.

    Google Scholar 

  62. Rolandi F., Francheschini R., Marabini A., Messina V., Cataldi A., Salvemini M., Barrera T.: Twenty-four-hour beta-endorphin secretory pattern in the elderly. Acta Endocrinol. (Copenh.) 115: 441–446, 1987.

    CAS  Google Scholar 

  63. Rosenthal M.J., Woodside W.F.: Nocturnal regulation of free fatty acids in healthy young and elderly men. Metabolism 37: 645–648, 1988.

    Article  PubMed  CAS  Google Scholar 

  64. Sherman B., Wysham C., Pfohl B.: Age-related changes in circadian rhythm of plasma cortisol in man. J. Clin. Endocrinol. Metab. 61: 439–443, 1985.

    Article  PubMed  CAS  Google Scholar 

  65. Touitou Y., Sulon J., Bogdan A., Touitou C., Reinberg A., Beck H., Sodoyez J-C., Demey-Ponsart E., Van Cauwenberg H.: Adrenal circadian system in young and elderly human subjects, a comparative study. J. Endocrinol. 93: 201–210, 1982.

    Article  PubMed  CAS  Google Scholar 

  66. Waltman C., Blackman M.R., Chrousos G.P., Riemann C., Harman S.M.: Spontaneous and glucocorticoid-inhibited adrenocorticotropic hormone and cortisol secretion in healthy young and old men. J. Clin. Endocrin. Metab. 73: 495–502, 1991.

    Article  CAS  Google Scholar 

  67. Halbreich W., Asnio G., Zumoff B., Nathan R., Shindledecker R.: Effect of age and sex on cortisol secretion in depressives and normals. Psychiatr. Res. 13: 221–229, 1984.

    Article  CAS  Google Scholar 

  68. Weiner M., Davis B., Mohs R., Davis K.: Influence of age and relative weight on cortisol suppression in normal subjects. Am. J. Psychiatry 144: 646–650, 1987.

    PubMed  CAS  Google Scholar 

  69. Zimmerman M., Coryll W.: The dexamethasone suppression test in healthy controls. Psychoneuroendocrinology 12: 245–251, 1987.

    Article  PubMed  CAS  Google Scholar 

  70. Maes M., Jacobs M., Suy E., Minner B., Rous J.: DST results in depression by means of urinary free cortisol secretion, dexamethasone levels, and age. Biol. Psychiatry 28: 349–356, 1990.

    Article  PubMed  CAS  Google Scholar 

  71. DeLeon M.J., McRae T., Tsai J.R., George A., Marcus D., Friedman M., Wolf A., McEwen B.: Abnormal cortisol response in Alzheimer’s disease linked to hippocampal atrophy. Lancet 391: 2–3, 1988.

    Google Scholar 

  72. Brandtstadter J., Baltes-Gotz B., Kirschbaum C., Hellhammer B.: Developmental and personality correlates of adrenocortical activity as indexed by salivary cortisol: Observations in the age range of 35 to 65 years. J. Psychosom. Res. 35: 173–185, 1991.

    Article  PubMed  CAS  Google Scholar 

  73. Touitou Y., Sulon J., Bogdan A., Reinberg A., Sodoyez J-C., Demey-Ponsart E.: Adrenocortical hormones, ageing and mental condition: seasonal and circadian rhythms of plasma 18-hydroxy-11 deoxycorticosterone, total and free cortisol and urinary corticosteroids. J. Endocrinol. 96: 5 -64, 1983.

    Google Scholar 

  74. Sparrow D., O’Connor G.T., Rosner B., DeMolles D., Weiss S.T.: A longitudinal study of plasma cortisol concentration and pulmonary function decline in men. The Normative Aging Study. Am. Rev. Respir. Dis. 147: 1345–1348, 1993.

    Article  PubMed  CAS  Google Scholar 

  75. Dilman V.M.: The hypothalamic control of aging and age-associated pathology. The elevation mechanism of aging. In: Everitt A.W., Burgess J.A. (Eds.), Hypothalamus, Pituitary and Aging. Charles C. Thomas, Springfield, IL. 1976, pp. 634–667.

    Google Scholar 

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Masoro, E.J. Glucocorticoids and aging. Aging Clin Exp Res 7, 407–413 (1995). https://doi.org/10.1007/BF03324354

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