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Pro-aging effects of chronic glucocorticoid signaling
Flavia Lambertucci1, Frederic Castinetti2, Isabelle Martins1
1Université Paris Cité, Sorbonne Université, Inserm U1138, Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Paris, France.
Cell Metabolism
|May 28, 2026
Summary
Sustained exposure to glucocorticoids (GCs) accelerates biological aging by disrupting cellular processes like autophagy and mitochondrial function. This review explores GC signaling
Area of Science:
- Endocrinology
- Gerontology
- Molecular Biology
Background:
- Glucocorticoids (GCs) are vital endocrine regulators with acute fluctuations being adaptive.
- Sustained GC exposure, from various stressors, significantly overlaps with biological aging processes.
- Chronic GC elevation is linked to accelerated age-related diseases.
Purpose of the Study:
- To review the mechanistic links between glucocorticoid signaling and systemic aging.
- To discuss strategies for mitigating age-accelerating effects of persistent GC exposure.
Main Methods:
- Literature review of mechanistic links between GC signaling and aging.
- Analysis of GC effects on hallmarks of aging.
- Examination of ACBP/DBI's role in GC-induced aging phenotypes.
Main Results:
- Prolonged GC signaling intersects with aging hallmarks: altered nutrient sensing, suppressed autophagy, impaired mitochondrial quality control, and promoted senescence.
- ACBP/DBI acts as a stress-induced inhibitor of macroautophagy, exacerbating GC excess consequences.
- Chronic GC elevation is clinically associated with earlier, severe age-related diseases.
Conclusions:
- Glucocorticoid signaling is a key driver of accelerated aging and age-related diseases.
- Understanding these mechanisms can inform strategies to counteract GC-induced aging.
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