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Review
. 2024 Dec;25(12):958-978.
doi: 10.1038/s41580-024-00727-x. Epub 2024 Apr 23.

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

Boshi Wang  1 , Jin Han  2 , Jennifer H Elisseeff  2 , Marco Demaria  3
Affiliations
Review

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

Boshi Wang et al. Nat Rev Mol Cell Biol. 2024 Dec.

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.

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Conflict of interest statement

Competing interests: M.D. is co-inventor of patents held by the Buck Institute for Research on Aging and by Cleara Biotech. M.D. is the scientific cofounder of Cleara Biotech and consultant for Oisin Biotechnologies. The M.D. laboratory currently receives research funding from Ono Pharmaceuticals. J.H.E. holds equity in Unity Biotechnology and Aegeria Soft Tissue and is an adviser for Tessera Therapeutics, HapInScience, and Font Bio.

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