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- W4366602833 abstract "Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to a pattern of chronic inflammation associated with aging and implicated in many age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor; encoded by the TNFSF13B gene), a SASP protein, in multiple senescence models. We first characterized BAFF production across different senescence paradigms, including senescent human diploid fibroblasts (WI-38, IMR-90) and monocytic leukemia cells (THP-1), and tissues of mice induced to undergo senescence. We then identified IRF1 (interferon regulatory factor 1) as a transcription factor required for promoting TNFSF13B mRNA transcription in senescence. We discovered that suppressing BAFF production decreased the senescent phenotype of both fibroblasts and monocyte-like cells, reducing IL6 secretion and SA-β-Gal staining. Importantly, however, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-κB and general SASP secretion, while in fibroblasts, BAFF contributed to the production and function of TP53 (p53). We propose that BAFF is elevated across senescence models and is a potential target for senotherapy." @default.
- W4366602833 created "2023-04-23" @default.
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- W4366602833 date "2023-04-21" @default.
- W4366602833 modified "2023-10-18" @default.
- W4366602833 title "Pleiotropic effects of BAFF on the senescence-associated secretome and growth arrest" @default.
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- W4366602833 doi "https://doi.org/10.7554/elife.84238" @default.
- W4366602833 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37083495" @default.
- W4366602833 hasPublicationYear "2023" @default.
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