Age-related Changes in the Regulation of the Hypothalamic-Pituitary Adrenal Axis: The Role of Personality Variables
The hypothalamic-pituitary adrenal (HPA) axis is one of the most important endocrine stress systems in humans. The HPA axis is activated upon the advent of a stressor, and as a consequence a cascade of hormones is released that serve different functions throughout the human organism, generally aimed at providing the necessary metabolic and immunomodulatory adjustments in response to a physiological or psychological stressor.
Basal secretion of the endproduct of the HPA axis, cortisol, follows a circadian rhythm, with the highest levels early in the morning and the lowest levels at night. Moreover, when released in response to stress, cortisol induces a negative feedback in the central nervous system (CNS) to terminate activity of the HPA axis when the stressor is no longer present. This normalization of activity is believed necessary to protect the organism from the long-term detrimental effects of chronic activation of the HPA axis.
Normal aging is accompanied by a number of changes in the regulation and activity of the HPA axis. Basal cortisol levels, especially at night around the time of the nadir, are increased, and feedback sensitivity to cortisol at different levels of the CNS is decreased.
The hippocampus is discussed as one of the structures involved in the changes of HPA regulation with aging. Receptors for glucocorticoids are primarily located in the hippocampus, and recent evidence suggests that basal cortisol and ACTH levels might be inversely associated with hippocampal volume, and thus might be at the origin of the age-related changes. Moreover, it has been shown that the inhibitory effect of glucocorticoid feedback on subsequent activity of the HPA axis is diminished in elderly subjects. Recently, we investigated cortisol levels during human aging together with CNS structures and personality variables. It appears that aging is not predictive of HPA axis regulation and structural CNS changes per se, but that specific personality types are less affected by age-related changes of the CNS and HPA axis regulation.
KeywordsFatigue Depression Corticosteroid Cortisol Dexamethasone
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- Collins L, Evans AC (1999) Animal: Automatic nonlinear image matching and anatomical labeling, Brain warping. Academic Press, San DiegoGoogle Scholar
- Dodt C, Theine KJ, Uthgenannt D, Born J, Fehm HL (1994) Basal secretory activity of the hypothalamo-pituitary-adrenocortical axis is enhanced in healthy elderly. An assessment during undisturbed night-time sleep. Eur J Endocrinol 131: 443–450Google Scholar
- Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL (2002) Age-related total gray matter and white matter changes in normal adult brain. Part II: Quantitative magnetization transfer ratio histogram analysis. AJNR Am J Neuroradiol 23: 1334–1341Google Scholar
- Haus E, Touitou Y (1994) Principles of clinical chronobiology. In: Touitou Y, Haus E (eds) Biologic rhythms in clinical and laboratory medicine. Springer Verlag, Berlin, 6–33Google Scholar
- Kirschbaum C, Prüssner JC, Stone AA, Federenko I, Gaab J, Lintz D, Schommer N, Hellhammer DH (1995) Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men. Psychosomatic Med 57: 468–474Google Scholar
- Molloy DW, Standish TI (1997) A guide to the standardized Mini-Mental State Examination. Int Psychogeriatr 9: 87–94; discussion 143–50Google Scholar
- Pruessner JC, Kohler S, Crane J, Pruessner M, Lord C, Byrne A, Kabani N, Collins DL, Evans AC (2003) Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the anatomical variability of the collateral sulcus. Cereb Cortex, in pressGoogle Scholar
- Pruessner JC, Li LM, Serles W, Pruessner M, Collins DL, Kabani N, Evans AC (2000) Volumetry of hippocampus and amygdala with high-resolution MRI and 3D analyzing software:Google Scholar
- minimizing the discrepancies between laboratories. Cereb Cortex 10: 433–442 Rosen G (1982) Alzheimer Disease Assessment Scale. Neuropsychologica 13: 34–43 Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocrinol Rev 7: 284–301Google Scholar
- Seeman TE, Robbins RJ (1994) Aging and hypothalamic-pituitary-adrenal response to challenge in humans. Endocrinol Rev 15: 233–260Google Scholar
- Talairach J, Tournoux P (1988) Co-planar stereotactic atlas of the human brain; 3-dimensional proportional system: an approach to cerebral imaging. Thieme, New YorkGoogle Scholar
- Teng EL, Chui HC, Gong A (1989) Comparisons between the Mini-Mental State Exam (MMSE) and its modified version - the 3MS test. In: Hasegama K, Homma A (eds) Psychogeriatrics: Biomedical and social advances. Selected proceedings of the fourth congress of the International Psychogeriatrics Association. Excerpta Medica, TokyoGoogle Scholar
- Van Cauter E, Coevorden Av, Blackman J (1990) Modulation of neuroendocrine release by sleep and circadian rhythmicity. In: Yen SSC, Vale WW (eds) Advances in neuroendocrine regulation of reproduction. Serono Symposium, Norwell, 113–122Google Scholar
- Wishart D (1998) Clustan graphics3: interactive graphics for cluster analysis. In: Gaul W, Locarek-Junge H (eds) Classification in the information age. Proceedings of the 22nd annual conference of the Society for Classification.. Springer, Berlin, pp. 268–275Google Scholar
- Wolf OT, Neumann O, Hellhammer DH, Geiben AC, Strasburger CJ, Dressendörfer RA, Pirke KM, Kirschbaum C (1997) Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men. J Clin Endocrinol Metab 82: 2363–2367PubMedCrossRefGoogle Scholar
- Wolf OT, Convit A, de Leon MJ, Caraos C, Qadri SF (2002) Basal hypothalamo-pituitary-adrenal axis activity and corticotropin feedback in young and older men: relationships to magnetic resonance imaging-derived hippocampus and cingulate gyrus volumes. Neuroendocrinology 75: 241–249PubMedCrossRefGoogle Scholar