4.5 Review

The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?

期刊

INFLAMMATION AND REGENERATION
卷 42, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s41232-022-00197-8

关键词

Cellular senescence; Senescence-associated secretory phenotype; cGAS-STING pathway; Toll-like receptor; Tumor microenvironment; Senolysis

资金

  1. AMED (Japan Agency for Medical Research and Development)
  2. AMED-CREST [JP21gm1010009]
  3. Japan Society for the Promotion of Science (JSPS) [19H04002]
  4. Takeda Science Foundation
  5. Yakult Bio-Science Foundation
  6. Research Grant of the Princess Takamatsu Cancer Research Fund [1825003]
  7. Grants-in-Aid for Scientific Research [19H04002] Funding Source: KAKEN

向作者/读者索取更多资源

Cellular senescence is an irreversible cell cycle arrest state that suppresses tumorigenesis, but recent studies have revealed that senescent cells also secrete substances that alter the tissue environment and contribute to chronic inflammation and cancer. This secretion phenomenon, known as senescence-associated secretory phenotype (SASP), can be observed in vitro and in vivo. The production of SASP factors is mainly mediated through the cGAS-STING pathway, and there are also external triggers for SASP induction.
Cellular senescence is a state of irreversible cell cycle arrest that can be induced by a variety of potentially oncogenic stimuli, including DNA damage. Hence, senescence has long been considered to suppress tumorigenesis, acting as a guardian of homeostasis. However, recent studies have revealed that senescent cells exhibit the secretion of a series of inflammatory cytokines, chemokines, growth factors, and matrix remodeling factors that alter the local tissue environment and contribute to chronic inflammation and cancer. This senescence phenotype is termed as senescence-associated secretory phenotype (SASP) and is observed not only in cultured cells in vitro but also in vivo. Recently, the physiological and pathological roles of SASP have been increasingly clarified. Notably, several studies have reported that the intrinsic mechanism of SASP factor production is predominantly mediated through the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway by aberrantly accumulated DNA fragments from the nucleus of senescent cells. In contrast, various extrinsic triggers of SASP also exist in vivo, for example, the SASP induction in hepatic stellate cells in the tumor microenvironment of obesity-associated liver cancer by the translocated gut microbial metabolites. Recently, the strategy for the elimination of senescent cells (senolysis) has attracted increasing attention. Thus, the role of SASP and the effects and outcomes of senolysis in vivo will be also discussed in this review.

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