Abstract
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.
Highlights
Of the roughly 150,000 people who die daily in the world, about two thirds die of age-related causes [1]
arginine vasopressin (AVP), corticotropin-releasing hormone (CRH), GR, Phospho-glucocorticoid receptor (p-GR), MR, 11βHSD1, 11beta hydroxysteroid dehydrogenase Type 2 (11βHSD2), and Hexose-6-phosphate dehydrogenase (H6PD) were all detected in the paraventricular nucleus (PVN)
CRH and p-GR were not correlated with ages (P > 0.05)
Summary
Of the roughly 150,000 people who die daily in the world, about two thirds die of age-related causes [1]. There are three main general theories of aging: genetic mutation, wear and tear (both proposed in the 1950s by Denham Harman [3]), and accumulated functional impairments in multiple tissues in the body [4,5]. In addition most studies are based across relatively small age windows of data making it difficult to draw conclusions on events across the periods lacking data between the documented stages. This is especially true if there are long time gaps between the data sets
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