"With age, the incidence of stress-related pathologies, in the etiopathogenesis of which endocrine dysfunctions play an important role, increases."
BUFFALO, NY — July 1, 2026 — A new review was published in Volume 18 of Aging on June 11, 2026, titled " Age-related dysfunctions of the neuroendocrine axes in nonhuman primates with depression-like and anxious behavior ."
The review, dedicated to the late Dr. Mikhail (Misha) Blagosklonny , was written by Nadezhda D. Goncharova from the Kurchatov Complex of Medical Primatology, National Research Center "Kurchatov Institute," Adler, Sochi, Russian Federation .
As people grow older, their risk of developing stress-related disorders—including depression, metabolic disease, cardiovascular disease, cognitive decline, and neurodegenerative conditions—increases substantially. However, not everyone ages in the same way. Some individuals appear more resilient to stress, while others develop endocrine and metabolic disturbances that may accelerate aging and disease. Understanding the biological mechanisms behind these differences could help identify people at greater risk and support more personalized approaches to healthy aging.
In this review, the author summarizes decades of experimental research investigating how aging affects two major neuroendocrine systems—the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-thyroid (HPT) axis—in nonhuman primates displaying either typical adaptive behavior or depression-like and anxiety-like behavior. Because rhesus monkeys closely resemble humans in their physiology, endocrine function, and behavior, they provide a valuable translational model for studying age-related changes that are difficult to examine in people.
The research shows that older monkeys with depression-like and anxiety-like behavior develop more pronounced dysfunction of the HPA axis than animals with standard behavior. These animals exhibited impaired negative feedback regulation, higher evening and nighttime cortisol levels, increased responses to acute stress, and greater activation of stress-related hormonal pathways. Together, these findings suggest impaired regulation of stress responses during aging.
The review also describes important age-related alterations in thyroid function. Older animals with depression-like and anxiety-like behavior showed lower thyroxine secretion, diminished thyroid responsiveness to hormonal stimulation, and evidence of impaired thyroid gland function. These endocrine changes were accompanied by greater insulin resistance, altered triglyceride metabolism, and reduced insulin secretion in overweight animals, indicating that stress-related neuroendocrine dysfunction may extend well beyond the brain.
Importantly, the findings suggest that behavioral characteristics may influence how endocrine systems age. Rather than experiencing identical biological changes over time, individuals with greater vulnerability to stress may develop more severe hormonal disturbances that contribute to age-related disease.
The review further highlights the value of functional endocrine testing. Dynamic assessments that measure hormonal responses to physiological stimulation or stress may provide more informative biomarkers of vulnerability than resting hormone levels alone, potentially allowing earlier identification of individuals at increased risk for stress-related disorders.
"Monitoring the behavior of individuals, as well as the functions of key adaptive endocrine systems, is promising for the early diagnosis of age-related pathology, its prevention and personalized treatment."
According to the author, integrating behavioral assessment with endocrine biomarkers could improve the identification of individuals who are especially susceptible to accelerated aging and stress-related disease. Such approaches may ultimately support more personalized prevention strategies and targeted interventions aimed at preserving healthy aging.
Overall, this review highlights that age-related changes in the body's stress and thyroid hormone systems are strongly influenced by behavioral characteristics. Findings from nonhuman primate studies suggest that individuals with depression-like and anxiety-like behavior may experience greater endocrine dysfunction during aging, providing valuable insight into mechanisms that could contribute to human age-related disease and inform future personalized medicine approaches.
Paper DOI: https://doi.org/10.18632/aging.206388
