Pleiotropic effects of BAFF on the senescence-associated secretome and growth arrest

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 invest...

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Published in:eLife Vol. 12
Main Authors: Rossi, Martina, Anerillas, Carlos, Idda, Maria Laura, Munk, Rachel, Shin, Chang Hoon, Donega, Stefano, Tsitsipatis, Dimitrios, Herman, Allison B, Martindale, Jennifer L, Yang, Xiaoling, Piao, Yulan, Mazan-Mamczarz, Krystyna, Fan, Jinshui, Ferrucci, Luigi, Johnson, Peter F, De, Supriyo, Abdelmohsen, Kotb, Gorospe, Myriam
Format: Journal Article
Language:English
Published: England eLife Science Publications, Ltd 21.04.2023
eLife Sciences Publications, Ltd
eLife Sciences Publications Ltd
Subjects:
Aging - genetics
Analysis
Animals
B-Cell Activating Factor - genetics
B-Cell Activating Factor - metabolism
B-Cell Activating Factor - pharmacology
BAFF
Biological response modifiers
Cell Biology
Cellular Senescence - genetics
Cytokines
Cytokines - metabolism
Developmental Biology
Growth
Humans
Inflammation
Leukemia
Mice
paracrine
Proteases
RNA
SASP
Secretome
senescence
Tumor proteins
Canada
senescence
BAFF
mouse
cell biology
developmental biology
paracrine
SASP
human
ISSN:2050-084X, 2050-084X
Online Access:Get full text
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Summary: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.
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.84238