Cellular senescence refers to a process in which certain cells, after becoming stressed or damaged, undergo a series of harmful changes. Cells may become senescent as a result of many variabilities, including misfolded proteins, DNA damage, replicative stress, and failed protein removal. Key features of senescent cells (SCs) are their resistance to apoptotic cell death and increases in secretory activity. These may contribute to the inducement of senescence in neighboring cells.  

Studies suggest that even a relatively small quantity of SCs may cause tissue dysfunction. Although rare in younger individuals, SCs increase in many tissues within the human body during the aging process. Tissues containing SCs may be more vulnerable to disease with increases in inflammation and decreases in function over time.  

A review article by Gao and colleagues explored the relationship between cellular senescence and adrenocortical health. The authors describe some age-related changes in the body that have been recently associated with the adrenal cortex. For instance, decreases in cortisol and increases in aldosterone over time have been associated with the aging process. The authors posit that cellular senescence may play a role in these age-related changes in adrenal function. 

The adrenal cortex consists of three layers: zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR). According to Gao and colleagues, each layer of the adrenal cortex has a different relationship with SCs. The SCs present in the ZG are believed to suppress some ability to produce aldosterone, which is a hormone critical to the renin-angiotensin-aldosterone system. Adrenal androgen production in the ZR may also be reduced in the presence of SCs. Cortisol-producing cells in the ZF may not inhibit cortisol production in the presence of SCs. However, more information is needed before clinical conclusions can be made.  

Healthy hormone production is critical to endocrine function and overall health. Disruptions in adrenocortical steroid production may lead to the development of more SCs. This can result in increased oxidative stress, damage to DNA, and telomere shortening. Telomeres are nucleotide sequences located at the ends of chromosomes. Shortened telomeres are associated with cellular senescence and cell cycle arrest.  

Age-related changes and cellular senescence have been shown to play roles in the development of certain chronic diseases, including osteoporosis and type 2 diabetes mellitus. Although further research is needed, cellular senescence may also influence age-related changes in the adrenal cortex. Certain bioactive molecules (including polyphenols) have been shown to support healthy aging and the body’s response to cellular senescence.  

By Colleen Ambrose, ND, MAT