Skip to main content
Log in

Chrono-neuroendocrine markers of the aging brain

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

The study of the neuroendocrine changes occurring in aging may give information about the CNS functions, and also explain the impaired plasticity of the aged organism. In 16 elderly women and in 14 young controls, the circadian rhythms of plasma melatonin, GH, PRL, ACTH and cortisol, and of oral temperature were simultaneously studied. The plasma cortisol circadian rhythm was also evaluated after DXM administration (1 mg orally at 23:00). The circadian profile of all the bioperiodic functions evaluated was clearly flattened in elderly subjects, and an impairment of the hormonal nocturnal secretion of GH, PRL and melatonin was apparent in elderly subjects when compared to young controls. The plasma ACTH levels throughout the 24-hour cycle were significantly higher in elderly than in young subjects. The cortisol circadian profile exhibited significantly higher values in the evening- and night-time in elderly subjects, compared to young controls; the cortisol nadir values were significantly age-related. A reduction of the sensitivity to DXM inhibition occurred in the elderly group. Both the selective impairment of nocturnal melatonin secretion, and the reduction of hypothalamo-pituitary-adrenal (HPA) sensitivity to steroid feedback might be considered as markers of aging brain. The neuroendocrine alterations of physiological aging may be ascribable to both the structural and neurochemical changes occurring in the CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Reiter R.J.: Pineal and associated neuroendocrine rhythms. Psychoneuroendocrinology 1: 255–263, 1976.

    Article  CAS  PubMed  Google Scholar 

  2. Axelrod J.: The pineal gland: a neurochemical transducer. Science 184: 1341–1344, 1974.

    Article  CAS  PubMed  Google Scholar 

  3. Grad B.R., Rozencwaig R.: The role of melatonin and serotonin in aging: update. Psychoneuroendocrinology 18: 283–295, 1993.

    Article  CAS  PubMed  Google Scholar 

  4. Halberg F.: Chronobiology. Ann. Rev. Physiol. 31: 675–725, 1969.

    Article  CAS  Google Scholar 

  5. Bingham C., Arbogast B., Guillaume G.C., Lee J.K., Halberg F.: Inferential statistical methods for estimating and comparing cosinor parameters. Chronobiologia 9: 397–439, 1982.

    CAS  PubMed  Google Scholar 

  6. Carrol B.J., Feinberg M., Gerden J.F.: A specific laboratory test for the diagnosis of melanchonia: standardization, validation and clinical utility. Arch. Gen. Psychiatry 38: 15–22, 1981.

    Article  Google Scholar 

  7. Scheving L.E., Roig C., Halberg F., Pauly J.E., Hand E.A.: Circadian variations in residents of a “senior citizens” home. In: Scheving L.E., Halberg F., Pauly J.E. (Eds.), Chronobiology. Igaku Shoin Ltd., Tokio, 1974, pp. 353–357.

    Google Scholar 

  8. Touitou Y., Reinberg A., Bogdan A., Auzeby A., Beck H., Touitou C.: Age-related changes in both circadian and seasonal rhythms of rectal temperature, with special reference to senile dementia of Alzheimer type. Gerontology 32: 110–118, 1986.

    Article  CAS  PubMed  Google Scholar 

  9. Reinberg A., Smolensky M.: Chronobiology and thermoreg-ulation. Pharmacol. Ther. 22: 425–464, 1983.

    Article  CAS  PubMed  Google Scholar 

  10. Martin J.B., Reichlin S.: Clinical neuroendocrinology, ed. 2, F.A. Davis Co., Philadelphia, 1987, pp. 379–421.

    Google Scholar 

  11. Halberg F.: Biological rhythms, hormones and aging. In: Vernadakis A., Timiras P.S. (Eds.), Hormones in development and aging. S.P. Medical and Scientific Books, New York, 1982, pp. 451–476.

    Google Scholar 

  12. Touitou Y., Fevre M., Bogdan A., Reinberg A., Touitou C., Beck H.: Age and mental health-related circadian rhythms of plasma levels of melatonin, prolactin, luteinizing hormone and follicle-stimulating hormone in man. J. Endocrinol. 91: 467–475, 1981.

    Article  CAS  PubMed  Google Scholar 

  13. Tapp E., Huxley M.: The histological appearance of the human pineal gland from puberty to old age. J. Pathol. 108: 137–144, 1972.

    Article  CAS  PubMed  Google Scholar 

  14. Brown G.M., Young S.N., Gauthier S., Tsui H., Grota L.J.: Melatonin in human cerebrospinal fluid in daytime; its origin and variation with age. Life Sci. 25: 929–936, 1979.

    Article  CAS  PubMed  Google Scholar 

  15. Iguchi H., Kato K.J., Ibayashi H.: Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J. Clin. Endocrinol. Metab. 55: 27–30, 1982.

    Article  CAS  Google Scholar 

  16. Sack R.L., Lewi A.J., Erb D.L., Voliner W.M., Singer C.M.: Human melatonin production decreases with age. J. Pineal Res. 3: 379–388, 1986.

    Article  CAS  PubMed  Google Scholar 

  17. Thomas D.R., Miles A.: Melatonin secretion and age. Biol. Psychiatry 25: 363–369, 1989.

    Article  Google Scholar 

  18. Sharma M., Palacios-Bois J., Schwartz G., Iksandar H., Thakur M., Quirion R., Nair N.P.V.: Circadian rhythms of melatonin and cortisol in aging. Biol. Psychiatry 25: 305–319, 1989.

    Article  CAS  PubMed  Google Scholar 

  19. Ferrari E., Solerte S.B., Dori D., Magri F., Fioravanti M., Bossolo P.A.: Changes of the circadian pattern of plasma melatonin related to aging. In: Reinberg A., Smolensky M., Labreque G. (Eds.), Annual Review Chronopharmacology. Pergamon Press, Oxford, New York, 1990, Vol. 7, pp. 7374.

    Google Scholar 

  20. Greenberg L., Weiss B.: Beta-adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. Science 201: 61–63, 1978.

    Article  CAS  PubMed  Google Scholar 

  21. Ebstein R.B., Stessman J., Eliaikim R., Menczel J.: The effect of age on beta-adrenergic function in man: a review. Isr. J. Med. Sci. 21: 302–311, 1985.

    CAS  PubMed  Google Scholar 

  22. Scarpace P.J., Abrass I.B.: Alpha and beta-adrenergic receptor function in the brain during senescence. Neurobiol. Aging 9: 53–58, 1988.

    Article  CAS  PubMed  Google Scholar 

  23. Hornykiewicz O.: Dopamine changes in the aging human brain: functional considerations. In: Agnoli A., Crepaldi G., Spano P.F., Trabucchi M. (Eds.), Aging brain and ergot alkaloids. Raven Press, New York, 1983, pp. 9–14.

    Google Scholar 

  24. Petkov V.D., Petkov V.V., Stancheva S.L.: Age-related changes in brain neurotransmission. Gerontology 34: 14–21, 1988.

    Article  CAS  PubMed  Google Scholar 

  25. Finkelstein W.J., Roffwarg H.P., Boyar R.M., Kream J., Hellman L.: Age-related change in the twenty-four hour spontaneous secretion of growth hormone. J. Clin. Endocrinol. Metab. 35: 665–670, 1972.

    Article  CAS  PubMed  Google Scholar 

  26. Rudman D., Kutner M.H., Rogers C.M., Lubin M.F., Fleming G.A., Bain R.P.: Impaired growth hormone secretion in the adult population. J. Clin. Invest. 67: 1361–1369, 1981.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Rudman D., Rao U.M.P.: The Hypothalamic-Growth Hor-mone-Somatomedin C axis: the effect of aging. In: Morley J., Korenman S.G. (Eds.), Endocrinology and Metabolism in the Elderly. Blackwell Scient. Publ., Boston, 1992, pp. 35–57.

    Google Scholar 

  28. Timiras P.S.: Neuroendocrine theories of aging: homeostasis and stress. In: Vernadakis A., Timiras P.S. (Eds.), Hormones in development and aging. Spectrum Publications Inc., Jamaica, New York, 1982, pp. 551–586.

    Google Scholar 

  29. Zakria F., Stern N., McGinty D., Beahm E., Littner M., Sowers J.R.: Effect of age on circadian rhythm of prolactin in normal men. Chronobiologia 15: 219–222, 1988.

    CAS  PubMed  Google Scholar 

  30. VanCoeverden A., Mockel J., Laurent E., Kerkhofs M., L’Hermite-Baleriaux M., Decoster C., Neve P., Van Cauter E.: Neuroendocrine rhythms and sleep in aging men. Am. J. Physiol. 260: E651–E661, 1991.

    Google Scholar 

  31. Marrama P., Carani C., Baraghini G.F., Volpe A., Zini D., Celani M.F., Montanini V.: Circadian rhythm of testosterone and prolactin in aging. Maturitas 4: 131–138, 1982.

    Article  CAS  PubMed  Google Scholar 

  32. Roland E., Magnani G., Sannia A., Barreca T.: Evaluation of PRL secretion in elderly subjects. Acta Endocrinol. (Co-penh.) 100: 351–357, 1982.

    Google Scholar 

  33. Krieger D.T., Silverberg A.I., Rizzo F., Krieger H.P.: Abolition of circadian periodicity of plasma 17-OH cs levels in the cat. Am J. Physiol. 215: 959–967, 1968.

    CAS  PubMed  Google Scholar 

  34. Greenspan S.L., Klibanski A., Rowe J.W., Elahi D.: Age alters pulsatile prolactin release: influence of dopaminergic inhibition. Am. J. Physiol. 258: E799–E804, 1990.

    CAS  PubMed  Google Scholar 

  35. Ferrari E., Bossolo P.A., Vailati A., Martinelli I., Rea A., Nosari I.: Variations circadiennes des effectes d’une substance vagolytique sur le système ACTH-secrétant chez l’homme. Ann. Endocrinol. (Paris) 38: 203–213, 1977.

    CAS  Google Scholar 

  36. Sapolsky R.M., Krey L.C., McEwen B.S.: The neuroendocri-nology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Rev. 7: 284–301, 1986.

    Article  CAS  PubMed  Google Scholar 

  37. Angelucci L., Patacchioli F.R., Scaccianoce S., Di Sciullo A., Catalani A., Taglialatela G., Ramacci M.T.: Hypothalamo-pituitary-adrenocortical function and process of brain aging. In: Nerozzi D., Goodwin F.K., Costa E. (Eds.), Hypotha-lamic Dysfunction in Neuropsychiatric Disorders. Raven Press, New York, 1987, pp. 293–304.

    Google Scholar 

  38. Kaplan A.S., Garfinkel P.E., Warsh J.J., Brown G.: Neuroen-docrine responses in bulimia. In: Ferrari E., Brambilla F. (Eds.), Disorders of eating behaviour: a psychoneuroendo-crine approach. Pergamon Press, Oxford, New York, 1986, pp. 241–245.

    Google Scholar 

  39. Wetterberg L.: The relationship between the pineal gland and the pituitary-adrenal axis in health, endocrine and psychiatric conditions. Psychoneuroendocrinology 8: 75–80, 1983.

    Article  CAS  PubMed  Google Scholar 

  40. Sachar E.J., Asnis G., Nathan S., Halbreich U., Tabrizi M.A., Halpern F.S.: Dextro-amphetamine and cortisol in depression. Morning plasma cortisol levels suppressed. Arch. Gen. Psychiatry 37: 755–757, 1980.

    Article  CAS  PubMed  Google Scholar 

  41. Tuomisto J., Mannisto P.: Neurotransmitter regulation of anterior pituitary hormones. Pharmacol. Rev. 37: 249–332, 1985.

    CAS  PubMed  Google Scholar 

  42. Halbreich U.: The circadian rhythm of cortisol and MHPG in depressive and normal. In: Halaris A. (Ed.), Chronobiology and Psychiatric Disorders. Elsevier, Amsterdam, 1987, pp. 49–73.

    Google Scholar 

  43. Dickson K.L., Hasty D.L.: Effects of the pineal gland in unilaterally adrenalectomized rats. Acta Endocrinol. (Copenh.) 70: 438–442, 1972.

    CAS  Google Scholar 

  44. Chakraborty S.: Exogenous melatonin may act as a reproductive-phase dependent modulator of the relationship in morphology between pineal and adrenal cortex in male Blos-somheaded Parakeet (Psittacula cyanocephala) and Indian Weaver Bird (Ploceus philippinus). Biol. Rhythm Res. 25: 121–132, 1994.

    Article  CAS  Google Scholar 

  45. Sanchez De La Pena S., Halberg F., Ungar F.: Pineal Chronomodulation- the feed-sideward. Clin. Chem. News-lett. 2: 129–135, 1982.

    Google Scholar 

  46. Milin J., Djakovic-Svajcer K., Demajo M.: Rat pineal gland suppresses the injection stress-reactive ACTH outflow. Horm. Metab. Res. 25:149–151, 1993.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrari, E., Magri, F., Locatelli, M. et al. Chrono-neuroendocrine markers of the aging brain. Aging Clin Exp Res 8, 320–327 (1996). https://doi.org/10.1007/BF03339588

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03339588

Key words

Navigation