Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-18 DOI:10.1038/s44319-025-00516-3

Dieu-Huong Hoang, Jessica Bouvière, Johanna Galvis, Pauline Moullé, Orane Mercier, Eugenia Migliavacca, Ananga Ghosh, Gaëtan Juban, Sophie Liot, Pascal Stuelsatz, Fabien Le Grand, Jérôme N Feige, Rémi Mounier, Bénédicte Chazaud

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引用次数: 0

Abstract

Muscle regeneration is impaired with aging, due to both intrinsic defects of muscle stem cells (MuSCs) and alterations of their niche. Here, we monitor the cells constituting the MuSC niche over time in young and old regenerating mouse muscle. Aging alters the expansion of all niche cells, with prominent phenotypes in macrophages that show impaired resolution of inflammation. RNA sequencing of FACS-isolated mononucleated cells uncovers specific profiles and kinetics of genes and molecular pathways in old versus young muscle cells, indicating that each cell type responds to aging in a specific manner. Moreover, we show that macrophages have an altered expression of Selenoprotein P (Sepp1). Macrophage-specific deletion of Sepp1 is sufficient to impair the acquisition of their restorative profile and causes inefficient skeletal muscle regeneration. When transplanted in aged mice, bone marrow from young WT mice, but not Sepp1-KOs, restores muscle regeneration. This work provides a unique resource to study MuSC niche aging, reveals that niche cell aging is asynchronous and establishes the antioxidant Selenoprotein P as a driver of age-related decline of muscle regeneration.

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免疫老化通过巨噬细胞来源的抗氧化硒蛋白P损害肌肉再生。

由于肌肉干细胞（MuSCs）的内在缺陷和其生态位的改变，肌肉再生随着年龄的增长而受损。在这里，我们监测构成MuSC生态位的细胞随着时间的推移在年轻和年老的再生小鼠肌肉。衰老改变了所有生态位细胞的扩张，巨噬细胞的突出表型显示炎症消退受损。facs分离的单核细胞的RNA测序揭示了老年和年轻肌肉细胞中基因和分子途径的特定特征和动力学，表明每种细胞类型以特定的方式对衰老作出反应。此外，我们发现巨噬细胞有硒蛋白P （Sepp1）的表达改变。巨噬细胞特异性的Sepp1缺失足以损害其恢复特性的获得，并导致骨骼肌再生效率低下。当移植到老年小鼠体内时，来自年轻WT小鼠的骨髓，而不是Sepp1-KOs，可以恢复肌肉再生。这项工作为研究MuSC生态位老化提供了独特的资源，揭示了生态位细胞老化是异步的，并建立了抗氧化剂硒蛋白P作为肌肉再生年龄相关下降的驱动因素。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.