Aging-related decrease of histone methyltransferase SUV39H1 in adipose-derived stem cells enhanced SASP

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI:10.1016/j.mad.2023.111868

Ruoyu Li , Yungshan Teng , Yuqing Guo , Jianhan Ren , Runze Li , Haotian Luo , Danying Chen , Zhicai Feng , Zheng Fu , Xuenong Zou , Weicai Wang , Chen Zhou

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引用次数: 0

Abstract

Aging-related diseases are closely associated with the state of inflammation, which is known as “inflammaging.” Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed the senescence-associated secretory phenotype (SASP). Epigenetic regulation, especially the structural regulation of chromatin, is closely linked to the regulation of SASP. In our previous study, the suppressor of variegation 3–9 homolog 1 (SUV39H1) was elucidated to interact with Lhx8 and determine the cell fate of mesenchyme stem cells. However, the function of SUV39H1 during aging and the underlying mechanism of its epigenetic regulation remains controversial. Therefore, the C57BL/6 J CAG-Cre; SUV39H1^fl/fl knockout mice and irradiation-induced cellular senescence model were built in this study to deepen the understanding of epigenetic regulation by SUV39H1 and its relation to SASP. In vivo and in vitro studies demonstrated that SUV39H1 decreased with aging and served as an inhibitor of SASP, especially IL-6, MCP-1, and Vcam-1, by altering H3K9me3 enrichment in their promoter region. These results provide new insights into the epigenetic regulation of SASP.

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脂肪来源干细胞中组蛋白甲基转移酶SUV39H1的衰老相关降低增强了SASP。

衰老相关疾病与炎症状态密切相关，炎症状态被称为“炎症”。衰老细胞具有代谢活性，例如分泌炎症细胞因子、趋化因子和生长因子，这被称为衰老相关分泌表型（SASP）。表观遗传学调控，特别是染色质的结构调控，与SASP的调控密切相关。在我们之前的研究中，杂色3-9同源物1的抑制剂（SUV39H1）被阐明与Lhx8相互作用并决定间充质干细胞的细胞命运。然而，SUV39H1在衰老过程中的功能及其表观遗传学调控的潜在机制仍然存在争议。因此，C57BL/6J CAG-Cre；本研究建立了SUV39H1fl/fl敲除小鼠和辐照诱导的细胞衰老模型，以加深对SUV39H1表观遗传学调控及其与SASP关系的理解。体内和体外研究表明，SUV39H1随着年龄的增长而减少，并通过改变启动子区H3K9me3的富集而成为SASP的抑制剂，尤其是IL-6、MCP-1和Vcam-1。这些结果为SASP的表观遗传学调控提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.