Adrenal Aging: Region-Specific Vulnerability And Proteostatic Decline - Mechanisms, Biomarkers, And Translational Opportunities
Our bodies rely on the adrenal glands, small organs that sit atop the kidneys, to manage stress, metabolism, immunity, and our daily rhythms. Despite their crucial role, how these glands age has been largely overlooked. Recent research, however, is shedding light on this process, revealing that adrenal aging is not a uniform decline but rather a targeted vulnerability within specific regions of the gland.
It turns out that two particular zones, the zona reticularis and zona glomerulosa, are more susceptible to age-related changes than others. This vulnerability stems from several factors, including a limited supply of cholesterol, which is essential for hormone production, and a breakdown in “proteostasis”—the cellular process responsible for maintaining healthy proteins. As we age, the body’s ability to manage and clear damaged proteins declines, leading to their accumulation and impairing cellular function.
These changes manifest as a decrease in important hormones like DHEA-S and aldosterone. While cortisol levels might appear stable on average, their daily rhythm can flatten, and there’s a higher chance of the gland producing cortisol autonomously, without proper regulation. At a cellular level, the vulnerable regions show signs of aging, immune activation, and problems with fat metabolism. The reduced ability to import cholesterol further exacerbates the decline in hormone production.
This research highlights that adrenal aging is a complex process influenced by factors like the aging of blood vessels and chronic low-grade inflammation. Understanding these mechanisms opens doors for developing new ways to measure “adrenal age” and potentially intervene to maintain adrenal health as we get older.
Source: link to paper