Potential regulators of the senescence-associated secretory phenotype during senescence and ageing

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Vol. 77; no. 11; pp. 2207 - 2218
• Main Authors: Han, Xiaojuan, Lei, Qing, Xie, Jiamei, Liu, Huanhuan, Sun, Haoran, Jing, Li, Zhang, Xiaohua, Zhang, Tianying, Gou, Xingchun
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 21-11-2022
• Subjects: Aging; Cell cycle; Cells; Chemokines; Chromatin remodeling; Cytokines; Extracellular matrix; Fibrosis; Growth factors; Immune clearance; Phenotypes; Senescence; Structure-function relationships; Tumor cells; Tumors; Wound healing; NcRNAs; Senescence; Epigenetic regulation; Transcription factor; SASP
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/glac097

Senescent cells express and secrete a variety of extracellular modulators that include cytokines, chemokines, proteases, growth factors and some enzymes associated with ECM remodeling, defined as the senescence-associated secretory phenotype (SASP). SASP reinforces senescent cell cycle arrest, stimulates and recruits immune cells for immune-mediated clearance of potentially tumorigenic cells, limits or induces fibrosis and promotes wound healing and tissue regeneration. On the other hand, SASP mediates chronic inflammation leading to destruction of tissue structure and function and stimulating the growth and survival of tumour cells. SASP is highly heterogeneous and the role of SASP depends on the context. The regulation of SASP occurs at multiple levels including chromatin remodelling, transcription, mRNA translation, intracellular trafficking and secretion. Several SASP modulators have already been identified setting the stage for future research on their clinical applications. In this review, we summarize in detail the potential signalling pathways that trigger and regulate SASP production during ageing and senescence.