Advancing Single-Cell Transcriptomic Analysis to Reveal Age-Related Skeletal Muscle Changes: A Systematic Review

Oct 24, 2025Aging and disease

Using Single-Cell Gene Analysis to Show Age-Related Changes in Skeletal Muscle

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Twenty-nine studies were included in this review, examining age-related changes in muscle at the single-cell level.

Muscle cell composition changes with age, showing fewer muscle stem cells, vascular cells, and Schwann cells, alongside an increase in myocytes and certain immune cells.
Age is associated with alterations in inflammation levels, collagen signaling, protein breakdown, and various cellular processes, including apoptosis and autophagy.
Delayed muscle regeneration in older individuals may be linked to issues with immune response, muscle formation, blood vessel development, and the remodeling of structural proteins.
Three treatments reviewed could partially reverse the dysfunction seen in muscle cells due to aging.
Investigating age-related muscle changes at the single-cell level may support the development of more effective treatments for sarcopenia.

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Population aging has become a widespread health problem that leads to huge socioeconomic burden. Skeletal muscle as an important component of motor system, gradually degenerates with age. Age-related muscle disorders, such as sarcopenia is associated with higher risks of falls, fracture, disability, and mortality in old people. As there is still no Food and Drug Administration (FDA) approved drug to treat sarcopenia, conducting research of in-depth mechanisms is warranted to develop novel treatments. The cutting-edge techniques single-cell and single-nuclei RNA sequencing can help to address this issue by discovering age-related changes of muscle at the single-cell level. This review aims to systematically explore current evidence of age-related muscle changes during normal aging, regeneration, and after treatments at the single-cell level. 29 studies were eligible and included in the current review according to the PRISMA guideline. The muscle cell composition was altered with age, such as diminished muscle stem cells (MuSCs), vascular cells, Schwann cells, and increased myocytes as well as some types of immune cells. Inflammation levels, collagen and extracellular matrix (ECM) signaling, protein catabolism, TGFβ signaling, apoptosis, and autophagy of MuSCs, myocytes, fibro-adipogenic progenitor cells, vascular cells, or immune cells were regulated with age. Delayed muscle regeneration of aged muscle was relied on disorders of cell-specific immune response, myogenesis, angiogenesis, and ECM remodeling. Three treatments involved in this review could reverse age-related dysfunction of muscle cells to some extent. Further research targeting age-related changes of muscle at the single-cell level is an important tool in assisting development of more effective treatments for sarcopenia.

Advancing Single-Cell Transcriptomic Analysis to Reveal Age-Related Skeletal Muscle Changes: A Systematic Review

Abstract

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