”Glucocorticoids, Cushing syndrome and cellular senescence: a mechanistic link to metabolic ageing”

Apr 9, 2026Endocrine connections

How Stress Hormones and Cushing Syndrome May Connect to Cell Aging and Metabolic Aging

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Chronic glucocorticoid excess is associated with alterations that resemble physiological ageing.

Glucocorticoids regulate immune responses, stress reactions, and metabolic pathways.
Excess glucocorticoids can lead to loss of tissue regeneration and impaired glucose and lipid balance.
Increased cardiovascular and neuropsychiatric vulnerability may occur with chronic glucocorticoid exposure.
Glucocorticoid excess is linked to cellular senescence and heightened inflammatory signaling.
Key metabolic organs affected include adipose tissue, skeletal muscle, liver, bone, and the brain.
The concept of glucocorticoid-driven metabolic ageing is emerging as a significant area of research.

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Glucocorticoids are key regulators of immune, stress and inflammatory responses, as well as of multiple metabolic pathways throughout life, and they play an anabolic role in tissue and organ development. Chronic glucocorticoid excess, whether due to endogenous Cushing syndrome, long-term pharmacological treatment or persistent stress, induces tissue-specific alterations that closely resemble those seen during physiological ageing. These shared changes include loss of tissue regenerative capacity, altered body composition, impaired glucose and lipid homeostasis and increased cardiovascular and neuropsychiatric vulnerability. Emerging evidence indicates that glucocorticoid excess can promote cellular senescence, amplify proinflammatory signalling and disrupt interorgan communication, thereby accelerating a state of metabolic ageing. This review synthesises current clinical and experimental data linking glucocorticoid excess with cellular senescence in key metabolic organs and systems, including adipose tissue, skeletal muscle, liver, bone, the cardiovascular system and the brain. Particular emphasis is placed on chronic neoplastic hypercortisolism as a human model, while also considering prolonged pharmacological glucocorticoid exposure and sustained stress as more prevalent, subclinical sources of hormonal overload. By integrating these lines of evidence, we outline the emerging concept of glucocorticoid-driven metabolic ageing and highlight potential mechanistic targets along the glucocorticoid axis and within senescence pathways. A better understanding of these mechanisms may inform strategies to prevent or mitigate age-related metabolic and cardiovascular complications in patients with Cushing syndrome, in individuals exposed to long-term glucocorticoid therapy and in the broader ageing population.

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”Glucocorticoids, Cushing syndrome and cellular senescence: a mechanistic link to metabolic ageing”

Abstract

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