Skeletal muscle aging is a complex biological process that involves coordinated changes in multiple cell types. Recent breakthroughs in single-cell sequencing technology have provided new perspectives regarding this process. Here, we systematically summarize current progress in single-cell technology with respect to skeletal muscle aging. We focused on specific molecular characteristics and interaction networks of muscle fiber, satellite and immune cells during aging. Aging skeletal muscles develop cellular heterogeneity such as a decline in stem cell function, formation of a chronic inflammatory microenvironment, and remodeling the extracellular matrix. We integrated multi-omics data to identify potential intervention targets and explored precise anti-aging strategies using single-cell data. Although this field has significantly progressed, persistent challenges include technical methods, data integration, and clinical translation. Future studies are needed to optimize single-cell analysis techniques, deepen understanding of cell interaction mechanisms, and promote the translation of related findings into clinical applications. These will provide vital references for understanding the molecular basis of muscle aging and developing new intervention methods.
Yanteng Wang, Yichen Yang, W. Guan et al.· Ageing Research Reviews· 0 citations
ABSTRACT Aim Skeletal muscle atrophy is tightly associated with maladaptive alterations in mitochondrial function and morphology. Itchy E3 ubiquitin‐protein ligase (ITCH) modulates mitochondria, and thrombospondin 1 (THBS1) positively regulates muscle atrophy, but their roles in muscle atrophy are unclear. Methods A muscle atrophy model was established in C57BL/6 mice via daily intraperitoneal injection of dexamethasone (Dex, 20 mg/kg). ITCH overexpression in skeletal muscle was achieved by adeno‐associated virus serotype 9 injection. C2C12 cells were treated with 50 μM Dex to mimic in vitro muscle atrophy. Skeletal muscle atrophy in mice was evaluated using hematoxylin–eosin staining and immunofluorescence staining. Mitochondrial damage was assessed via transmission electron microscopy, succinate dehydrogenase staining, and JC‐1 staining. Immunoprecipitation‐liquid chromatography/mass spectrometry, molecular docking, and co‐immunoprecipitation were used to investigate the interaction between ITCH and THBS1. Phosphoproteomics analysis was performed to detect the THBS1 downstream proteins. Results Dex treatment downregulated ITCH expression in skeletal muscle. ITCH overexpression increased body weight, muscle mass, and muscle strength, downregulated the expression of atrophy‐related genes (Atrogin‐1, Mstn, MuRF‐1), and promoted mitochondrial biogenesis. The results of the C2C12 cells were consistent with those obtained in vivo. Proteomic profiling and Co‐IP confirmed ITCH–THBS1 interaction and subsequent THBS1 ubiquitination. THBS1 knockdown reduced the expression of Atrogin‐1 and MuRF‐1 and inhibited the phosphorylation of JUN and Map3k7, whereas THBS1 overexpression reversed the ITCH‐mediated improvement in mitochondrial biogenesis. Conclusion ITCH enhances mitochondrial biogenesis and mitigates Dex‐induced muscle atrophy by promoting the ubiquitin‐dependent degradation of THBS1 and subsequent inhibition of downstream JUN/Map3k7 phosphorylation.
Wan Yu, Yanteng Wang, Na Li et al.· Acta Physiologica· 0 citations
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