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Peer-reviewedCC BY-NC-NDCell Metabolism

Pro-aging effects of chronic glucocorticoid signaling

  • Flavia Lambertucci1
  • Frédéric Castinetti2
  • Isabelle Martins1
  • Carlos López-Otı́n3
  • Guido Kroemer
  1. 1Université Paris Cité, Sorbonne Université, Inserm U1138, Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Paris, France
  2. 2Assistance Publique Hôpitaux de Marseille, Department of Endocrinology, La Conception Hospital, Marseille, France
  3. 3Université Paris Cité, Sorbonne Université, Inserm U1138, Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Paris, France; Facultad de Ciencias de la Vida y la Naturaleza, Universidad Nebrija, Madrid 28248, Spain
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Abstract

Glucocorticoids (GCs) are essential endocrine regulators coordinating stress responsiveness, metabolic flexibility, inflammatory resolution, and circadian physiology. While acute GC fluctuations are adaptive, sustained exposure (arising from psychosocial stress, circadian disruption, obesity, chronic inflammation, neoplasms, or steroid therapy) elicits pleiotropic effects that overlap with biological aging. Prolonged GC signaling intersects with multiple hallmarks of aging by altering nutrient sensing, suppressing autophagy, impairing mitochondrial quality control, and promoting cellular senescence. In this context, the GC-responsive polypeptide ACBP/DBI (acyl-coenzyme A [CoA]-binding protein/diazepam-binding inhibitor) has emerged as a stress-induced inhibitor of macroautophagy that amplifies several metabolic and immune consequences of GC excess linked to aging phenotypes. Clinically, chronic GC elevation is associated with earlier and more severe manifestations of age-related diseases, including metabolic syndrome, osteoporosis, sarcopenia, neurodegeneration, cardiovascular disease, immunosenescence, and cancer. Here, we review mechanistic links between GC signaling and systemic aging and discuss strategies to mitigate the age-accelerating consequences of persistent GC exposure.

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Cite

BibTeXRIS
BibTeX
@article{lambertucci2026proaging,
  title = {{Pro-aging effects of chronic glucocorticoid signaling}},
  author = {Flavia Lambertucci and Frédéric Castinetti and Isabelle Martins and Carlos López-Otı́n and Guido Kroemer},
  journal = {Cell Metabolism},
  year = {2026},
  month = may,
  doi = {10.1016/j.cmet.2026.05.002},
  url = {https://doi.org/10.1016/j.cmet.2026.05.002},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Pro-aging effects of chronic glucocorticoid signaling
AU  - Flavia Lambertucci
AU  - Frédéric Castinetti
AU  - Isabelle Martins
AU  - Carlos López-Otı́n
AU  - Guido Kroemer
PY  - 2026
DA  - 2026/05/28
JO  - Cell Metabolism
DO  - 10.1016/j.cmet.2026.05.002
UR  - https://doi.org/10.1016/j.cmet.2026.05.002
AB  - Glucocorticoids (GCs) are essential endocrine regulators coordinating stress responsiveness, metabolic flexibility, inflammatory resolution, and circadian physiology. While acute GC fluctuations are adaptive, sustained exposure (arising from psychosocial stress, circadian disruption, obesity, chronic inflammation, neoplasms, or steroid therapy) elicits pleiotropic effects that overlap with biological aging. Prolonged GC signaling intersects with multiple hallmarks of aging by altering nutrient sensing, suppressing autophagy, impairing mitochondrial quality control, and promoting cellular senescence. In this context, the GC-responsive polypeptide ACBP/DBI (acyl-coenzyme A [CoA]-binding protein/diazepam-binding inhibitor) has emerged as a stress-induced inhibitor of macroautophagy that amplifies several metabolic and immune consequences of GC excess linked to aging phenotypes. Clinically, chronic GC elevation is associated with earlier and more severe manifestations of age-related diseases, including metabolic syndrome, osteoporosis, sarcopenia, neurodegeneration, cardiovascular disease, immunosenescence, and cancer. Here, we review mechanistic links between GC signaling and systemic aging and discuss strategies to mitigate the age-accelerating consequences of persistent GC exposure.
SN  - 1550-4131
SN  - 1932-7420
ER  -