肌萎缩
骨骼肌
衰老
纤维化
细胞外基质
生物
巨噬细胞
表型
医学
内科学
内分泌学
细胞生物学
体外
遗传学
基因
作者
Norika Liu,Joshua T. Butcher,Atsushi Nakano,Andrea del Campo
出处
期刊:Aging
[Impact Journals, LLC]
日期:2023-05-25
卷期号:15 (10): 4035-4050
标识
DOI:10.18632/aging.204750
摘要
One of the most pronounced changes in the elderly is loss of strength and mobility due to the decline of skeletal muscle function, resulting in a multifactorial condition termed sarcopenia. Although significant clinical changes begin to manifest at advanced ages, recent studies have shown that changes at the cellular and molecular level precede the symptomatology of sarcopenia. By utilizing a single-cell transcriptomic atlas of mouse skeletal muscle across the lifespan, we identified a clear sign of immune senescence that presents during middle age. More importantly, the change in macrophage phenotype in middle age may explain the changes in extracellular matrix composition, especially collagen synthesis, that contributes to fibrosis and overall muscle weakness with advanced age. Our results show a novel paradigm whereby skeletal muscle dysfunction is driven by alterations in tissue-resident macrophages before the appearance of clinical symptoms in middle-aged mice, providing a new therapeutic approach via regulation of immunometabolism.
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