免疫衰老
生物
衰老
细胞生物学
细胞因子
炎症
早衰
免疫系统
信号转导
免疫学
巨噬细胞
遗传学
体外
作者
Zhou Zhao,Jingfei Yao,Dongmei Wu,Xun Huang,Yushuang Wang,Xinmeng Li,Qiang Lu,Yifu Qiu
出处
期刊:Immunity
[Elsevier]
日期:2024-03-01
卷期号:57 (3): 513-527.e6
被引量:10
标识
DOI:10.1016/j.immuni.2024.01.001
摘要
Summary
Accumulation of senescent cells in organs and tissues is a hallmark of aging and known to contribute to age-related diseases. Although aging-associated immune dysfunction, or immunosenescence, is known to contribute to this process, the underlying mechanism remains elusive. Here, we report that type 2 cytokine signaling deficiency accelerated aging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophages from senescence. Mechanistically, activated STAT6 promoted the expression of genes involved in DNA repair both via homologous recombination and Fanconi anemia pathways. Conversely, STAT6 deficiency induced release of nuclear DNA into the cytoplasm to promote tissue inflammation and organismal aging. Importantly, we demonstrate that IL-4 treatment prevented macrophage senescence and improved the health span of aged mice to an extent comparable to senolytic treatment, with further additive effects when combined. Together, our findings support that type 2 cytokine signaling protects macrophages from immunosenescence and thus hold therapeutic potential for improving healthy aging.
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