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Updated: May 3, 2026
Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
A comprehensive single-cell RNA transcriptomic analysis identifies a unique SPP1+ macrophages subgroup in aging
Wen Bi1, Mengyue Yang2, Mengjia Shi3
1Department of Sports Medicine, The Sixth Affiliated Hospital of Shenzhen University, Shenzhen Nanshan People's Hospital, Shenzhen, 518052, China.
Abstract:
Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging.
Insights
Aging skeletal muscle shows increased SPP1+ macrophages, linked to senescence and fat accumulation. Senolytic treatment with dasatinib + quercetin reduced these macrophages, offering a potential therapeutic target for age-related muscle weakness.
Area of Science:
- Cellular senescence
- Muscle biology
- Immunology
Background:
- Skeletal muscle (SkM) senescence contributes to age-related weakness and disability.
- Macrophage (Mac) populations within SkM play diverse roles in aging.
- An imbalance between damage and repair processes is implicated in declining SkM function.
Purpose of the Study:
- To compare metabolic pathways and biological functions of cells in young and old mouse SkM.
- To identify and characterize specific macrophage subgroups in aged SkM.
- To investigate the therapeutic potential of targeting senescence-related macrophages.
Main Methods:
- Comprehensive single-cell transcriptomic analysis of young and old mouse SkM.
- Identification and characterization of macrophage subgroups.
- Quantitative analysis of SPP1+ macrophage proportion in mouse quadriceps.
- Assessment of senotherapeutic drug combination (dasatinib + quercetin) effects.
Main Results:
- A unique macrophage subgroup expressing high levels of SPP1 was identified in old mouse SkM, exhibiting senescence and adipogenesis features.
- The proportion of SPP1+ macrophages significantly increased in the quadriceps of old mice.
- The senotherapeutic combination of dasatinib + quercetin markedly reduced the proportion of SPP1+ macrophages.
Conclusions:
- SPP1+ macrophages represent a distinct cellular component associated with SkM aging and adipogenesis.
- Targeting SPP1+ macrophages with senolytics like dasatinib + quercetin may offer a novel therapeutic strategy for SkM aging.
- This study highlights SPP1+ macrophages as a potential senotherapeutic target for combating age-related muscle decline.
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