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Updated: Sep 14, 2025
In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P
Dieu-Huong Hoang1, Jessica Bouvière1, Johanna Galvis1
1Institut NeuroMyoGène, Unité Physiopathologie et Génétique du Neurone et du Muscle, Université Claude Bernard Lyon 1, Inserm U1315, CNRS 5261, Lyon, France.
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.
Insights
Aging impairs muscle regeneration by affecting muscle stem cell niches, particularly macrophages. The antioxidant Selenoprotein P (Sepp1) is crucial for macrophage function and restoring muscle repair in older mice.
Area of Science:
- Skeletal muscle biology
- Cellular and molecular aging
- Immunology
Background:
- Muscle regeneration declines with age due to intrinsic defects in muscle stem cells (MuSCs) and their niche.
- Aging affects MuSC niche cells, leading to impaired inflammation resolution, particularly in macrophages.
Purpose of the Study:
- To investigate age-related changes in the MuSC niche during muscle regeneration.
- To identify molecular mechanisms underlying impaired regeneration in aged muscle.
- To determine the role of Selenoprotein P (Sepp1) in age-related muscle decline.
Main Methods:
- Monitoring MuSC niche cells in young and old regenerating mouse muscle.
- RNA sequencing of FACS-isolated mononucleated cells.
- Macrophage-specific gene deletion and bone marrow transplantation experiments.
Main Results:
- Aging alters niche cell expansion, with macrophages showing impaired inflammation resolution.
- Distinct gene expression profiles and kinetics were observed in aged versus young muscle cells.
- Macrophages exhibit altered Sepp1 expression with aging.
- Macrophage-specific Sepp1 deletion impairs restorative capacity and skeletal muscle regeneration.
- Young wild-type bone marrow transplantation restored regeneration in aged mice, unlike Sepp1-knockouts.
Conclusions:
- Muscle stem cell niche aging is asynchronous, with macrophages playing a key role.
- Selenoprotein P is identified as a critical factor driving age-related decline in muscle regeneration.
- Targeting Sepp1 in macrophages may offer therapeutic potential for improving muscle repair in the elderly.
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