Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.10.25.513730v1?rss=1

Authors: Rossi, M., Anerillas, C., Idda, M. L., Munk, R., Shin, C. H., Donega, S., Tsitsipatis, D., Herman, A. B., Martindale, J. L., Yang, X., Piao, Y., Mazan-Mamczarz, K., Fan, J., Ferrucci, L., De, S., Abdelmohsen, K., Gorospe, M.

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), a SASP protein, in multiple senescence models. We first characterized BAFF production across different senescence models, 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 response factor 1) as a transcription factor required for promoting BAFF mRNA transcription in senescence. We discovered that suppressing BAFF production decreased the senescent phenotype of both fibroblasts and monocyte-derived THP-1 cells, overall reducing IL6 secretion, SA-{beta}-Gal staining, and {gamma}-H2AX accumulation. Importantly, however, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-{kappa}B 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.

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