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Aging (Albany NY). 2017 May 9;9(5):1375-1385. doi: 10.18632/aging.101235.

A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging.

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Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
Texas Pregnancy and Life-course Health Research Center, Department of Animal Sciences, University of Wyoming, Laramie, WY 82071, USA.
Department of Statistics, University of Wyoming, Laramie, WY 82071, USA.
Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
Department of Animal Sciences, University of Wyoming, Laramie, WY 82071, USA.


Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.


HPA axis (hypothalamus-pituitary-adrenal); aging; baboon; glucocorticoids; paraventricular nucleus

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