The senescence-associated secretory phenotype and its physiological and pathological implications

Boshi Wang; Jin Han; Jennifer H Elisseeff; Marco Demaria

doi:10.1038/s41580-024-00727-x

The senescence-associated secretory phenotype and its physiological and pathological implications

Nat Rev Mol Cell Biol. 2024 Apr 23. doi: 10.1038/s41580-024-00727-x. Online ahead of print.

Authors

Boshi Wang¹, Jin Han², Jennifer H Elisseeff², Marco Demaria³

Affiliations

¹ European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, Netherlands.
² Translational Tissue Engineering Center, Wilmer Eye Institute, and Department of Biomedical Engineering, John Hopkins University School of Medicine, Baltimore MD, MD, USA.
³ European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, Netherlands. m.demaria@umcg.nl.

PMID: 38654098
DOI: 10.1038/s41580-024-00727-x

Abstract

Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the composition, dynamics and heterogeneity of the SASP as well as the mechanisms underlying its induction and regulation. We describe the various biological properties of the SASP, its beneficial and detrimental effects in different physiological and pathological settings, and its impact on overall health span. Finally, we discuss the use of the SASP as a biomarker and of SASP inhibitors as senomorphic interventions to treat cancer and other age-related conditions.

Publication types

Review