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Cited by 218Muscle Physiology and DisordersSingle-cell and spatial transcriptomicsNutrition and Health in Aging

Human skeletal muscle aging atlas

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Kedlian, Veronika R., Wang, Yaning, Liu, Tianliang, Chen, Xiaoping, Bolt, Liam, Tudor, Catherine, Shen, Zhuojian, Fasouli, Eirini S. +24 more·2024·Nature Aging
DOI 10.1038/s43587-024-00613-3PMC PMC11108788
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Abstract

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

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  • This gradual aging-related reduction in SM mass contributes towards an overall decline in SM strength, function, and regenerative capacity, and is a key contributor to aging-related frailty.

    “This gradual aging-related reduction in SM mass (trending towards a state of sarcopenia) contributes towards an overall decline in SM strength, function, and regenerative capacity, and is a key contributor to aging-related frailty with important implications for global health and economics [29,30,31,32].”

    From Optimised Skeletal Muscle Mass as a Key Strategy for Obesity Management (2025) · cites this paper as [32]

    The Main section reports age-related loss of muscle mass and strength, sarcopenia, and reduced muscle stem-cell activation and proliferation. It does not establish that loss of mass itself causes the declines in strength, function, or regenerative capacity; nor does the cited passage address economic implications. The Main section links skeletal muscle aging to falls and fractures, but does not directly characterize loss of mass as a key cause of frailty. (LLM, conf=0.85)

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Authors
Kedlian, V. R., Wang, Y., Liu, T., Chen, X., Bolt, L., Tudor, C., Shen, Z., Fasouli, E. S., Prigmore, E., Kleshchevnikov, V., Pett, J. P., Li, T., Lawrence, J. E. G., Perera, S., Prete, M., Huang, N., Guo, Q., Zeng, X., Yang, L., Polański, K., Chipampe, N.-J., Dabrowska, M., Li, X., Bayraktar, O. A., Patel, M., Kumasaka, N., Mahbubani, K. T., Xiang, A. P., Meyer, K. B., Saeb-Parsy, K., Teichmann, S. A., & Zhang, H.
Affiliations
  • Wellcome Sanger Institute (GB)
  • Sun Yat-sen University (CN)
  • University of Cambridge (GB)
Corresponding author
  • Teichmann, Sarah A.
  • Zhang, Hongbo
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2024-04-15
Volume
4
Issue
5
Pages
727-744
ISSN
2662-8465 (ISSN-L)
DOI
10.1038/s43587-024-00613-3
PMC
PMC11108788
OpenAlex
W4394812780
Cited by
218
References
17
Citations by year
2026: 107 · 2025: 87 · 2024: 23 · 2022: 1
FWCI
29.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (WT211276/Z/18/Z, WT206194, 220540/Z/20/A)
  • National Natural Science Foundation of China (32000840, 31871370)
  • Natural Science Foundation of Guangdong Province (2021A1515012065)
  • EC | Horizon 2020 Framework Programme (101026233)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
skeletal muscle aging, intercostal muscles, single-cell atlas, single-nucleus RNA sequencing, muscle stem cells, ribosome biogenesis, MCP-1, neuromuscular junction, reinnervation, myofiber regeneration, muscle microenvironment, sarcopenia, age-related frailty
MeSH terms
Adult, Aged, Aging, Animals, Female, Humans, Male, Middle Aged, Neuromuscular Junction, Muscle, Skeletal, Mice, Sarcopenia

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