Aging and the adrenal cortex

Area of Science:

• Endocrinology
• Neuroscience
• Aging Research

Background:

• Aging is associated with altered adrenal steroidogenesis, including increased cortisol and decreased androgens.
• Cortisol excess is implicated in cognitive decline and hippocampal damage, driving interest in hormone replacement for healthy aging.
• Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are key adrenal steroids with complex roles throughout the lifespan.

Purpose of the Study:

• To explore the intricate relationship between adrenal glucocorticoid and androgen secretion during human aging.
• To investigate the potential impact of DHEA-S on liver metabolism and its implications for health and disease.
• To examine the dynamic changes in the cortisol/DHEA-S ratio across the lifespan and its significance.

Main Methods:

• Review of existing literature on adrenal steroid function in aging.
• Analysis of recent studies on DHEA-S interaction with peroxisome proliferator-activated receptor alpha (PPAR alpha).
• Examination of lifespan changes in cortisol and DHEA-S levels and their ratio.

Main Results:

• DHEA-S, but not DHEA, activates PPAR alpha in the liver, suggesting a role in regulating fatty acid metabolism and gene expression.
• DHEA-S may contribute to the chemoprotective effects of endogenous steroids.
• The cortisol/DHEA-S ratio exhibits a U-shaped curve across the lifespan, with higher ratios in infancy and old age.

Conclusions:

• Adrenal steroid dynamics, particularly the interplay between cortisol and DHEA/DHEA-S, are critical throughout human aging.
• DHEA-S has potential physiological roles in liver metabolism and may possess protective properties.
• Further research into the simultaneous study of cortisol and DHEA-S is warranted to understand their combined impact on health and aging.