Cell senescence, the senescence-associated secretory phenotype, and cancers

Sep 24, 2026

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Cellular senescence is a fate triggered by diverse stresses, characterized by an essentially irreversible replicative arrest and a capacity to reshape tissues. Early work dismissed it as a culture artifact, but later findings tied senescence to human health, including cancer defense and—when persistent—contributions to multiple age-related disorders. Senescent cells remain metabolically active and resist death, producing a SASP that develops over days, drives inflammation and fibrosis, attracts immune cells, and can promote cancer progression via SASP-dependent paracrine signaling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Perspective

Cellular senescence and its relevance to health

Senescence-associated secretory phenotype (SASP)

Immune clearance and persistent senescent cells

SASP links to cancer progression and therapy implications

OPEN ACCESS Citation: Langhi Prata LGP, Tchkonia T, Kirkland JL (2023) Cell senescence, the senescence-associated secretory phenotype, and cancers. PLoS Biol 21(9): e3002326 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pbio.3002326 Published: September 21, 2023 Copyright: © 2023 Langhi Prata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: L.G. P. L. P. was supported by NIH grant T32 5T32AG049672-07. J. L. K. and T.T. were supported by NIH grants R37AG 13925 and R33AG 61456, the Connor Group, Robert J. and Theresa W. Ryan, and the Noaber and Ted Nash Long Life Foundations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: J. L. K. and T.T. have a financial interest related to this research. Patentson senolytic drugs are held by Mayo Clinic. L.G. P. L. P. declared that no competing interests exist. PERSPECTIVE Cell senescence, the senescence-associated secretory phenotype, and cancers Larissa G. P. Langhi Prata1, Tamar Tchkonia1, James L. Kirkland1,2 * 1 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America * [kirkland.james@mayo.edu](kirkland.james@mayo.edu) Cellular senescence is a cell fate caused by multiple stresses. A 2008 article in PLOS Biology reported a senescence-associated secretory phenotype that can promote inflammation and cancer, eventually enabling the development of senolytic drugs. This article is part of the PLOS Biology 20th Anniversary Collection. Cellular senescence was first described in 1961 by Hayflick and Moorehead [ 1] . At first, it was dismissed by many as a phenomenon or artefact related to repeated replication of cultured cells. The relevance of cellular senescence to human health took decades to uncover. It is now appreciated that senescent cells, which exist in a state of essentially irreversible replicative arrest, can occur in response to stresses such as telomeric dysfunction, DNA damage, oncogene expression, metabolic stresses, cytotoxic chemotherapy, radiation, and many others [2] . Almost any vertebrate cell type, including terminally differentiated cells and cancer cells, can become senescent. Senescence can be beneficial: it appears important in tissue remodeling, such as after injury or during embryogenesis and, importantly, can serve as a defense against cancer development. Indeed, preventing the generation ofsenescent cells by interfering with expression or activity of senescence-inducing regulators (such as p16INK4a, Rb, p21CIP1, and p53) can accelerate cancer development. However, persisting senescent cells can be harmful and appear to be root cause contributors to multiple disorders and diseases across the lifespan that account for considerable morbidity and the bulk of health care expenditures [3] . Beneficial effects of being able to form senescent cells when needed may have evolved at the expense of adverse effects caused by persisting senescent cells in older, post-reproductive individuals, who have lived beyond the point at which natural selection principally acts [4,5] . Senescent cells are metabolically active, quite resistant to cell death and, as reported in a seminal 2008 paper in PLOS Biology by Copp´e and colleagues [5], express a senescence-associated secretory phenotype (SASP) . As shown in that paper, the SASP takes 4 days or more to develop fully in cultured fibroblasts. It can include a range offactors that leads to damage, inflammation, fibrosis, metabolic dysfunction, spread of senescence to other cells, and multiple other effects at the tissue level. Copp´e and colleagu

FAQs

What triggers cellular senescence and what is its key cellular feature?

Cellular senescence is caused by multiple stresses and results in an essentially irreversible replicative arrest. It can occur across many vertebrate cell types, including terminally differentiated cells and cancer cells.

What is the senescence-associated secretory phenotype (SASP)?

Senescent cells express a SASP, produced after senescence induction and taking 4 days or more to develop fully in cultured fibroblasts. It includes factors that can cause damage, inflammation, fibrosis, metabolic dysfunction, and spread of senescence.

How can persistent senescent cells influence cancer?

Persistent senescent cells can promote cancer progression through SASP-dependent paracrine effects, including epithelial-to-mesenchymal transitions and increased invasiveness. SASP factors such as IL-6 and IL-8 contribute to this pro-cancer signaling.

Sep 24, 2026

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