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Related Experiment Video

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Single-Cell RNAseq Identifies Heterogeneity in Myoblasts From Older Adults With Differences Related to Muscle Mass

Mark A Burton1,2, Emma S Garratt1,2, Hanan Y Sharkh1,3

  • 1Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.

Journal of Cachexia, Sarcopenia and Muscle
|February 18, 2026
PubMed
Summary

Aging muscle stem cells show significant transcriptional differences. In older adults with low muscle mass and strength, these cells tend to become fibrogenic or stressed, impacting muscle health.

Keywords:
ageingcell heterogeneitymyoblastssarcopeniasingle‐cell transcriptomicsskeletal muscle

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Area of Science:

  • Skeletal muscle biology
  • Cellular and molecular aging
  • Transcriptomics

Background:

  • Aging leads to muscle mass and function decline, affecting metabolic health, frailty, and independence.
  • Investigating transcriptional heterogeneity in muscle stem cells (myoblasts) of older adults is crucial.
  • Understanding variations between healthy and low-muscle-mass individuals is key.

Purpose of the Study:

  • To explore the transcriptional heterogeneity of human proliferating muscle satellite/stem cells (myoblasts) in older adults.
  • To determine how this heterogeneity differs between healthy individuals and those with reduced muscle mass and function.

Main Methods:

  • Single-cell transcriptomic analysis of myoblasts from 132 older adults (72-83 years).
  • Uniform Manifold Approximation and Projection (UMAP) clustering to identify distinct cell populations.
  • Gene Ontology and pseudotime trajectory analyses to understand cell functions and lineages.
  • Differential gene expression analysis correlated with appendicular lean-mass index (ALMi) and grip strength.

Main Results:

  • Thirteen distinct myoblast transcriptional clusters were identified.
  • Clusters associated with muscle development and RNA processing were more abundant in individuals with higher grip strength and ALMi.
  • Cells from individuals with low ALMi and grip strength were more likely to progress towards stressed, pre-senescent, or fibrogenic states.

Conclusions:

  • Significant transcriptional heterogeneity exists within skeletal muscle myoblasts of older adults.
  • Myoblasts from individuals with low muscle mass and strength exhibit a propensity towards fibrogenic or stressed cellular states.
  • These findings highlight cellular mechanisms underlying age-related muscle decline.