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Cited by 6Genetics, Aging, and Longevity in Model OrganismsMuscle Physiology and DisordersNutrition and Health in Aging

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Metabolic analysis of sarcopenic muscle identifies positive modulators of longevity and healthspan in C. elegans

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Jonk, Steffi M., Nicol, Alan, Chrysostomou, Vicki, Lardner, Emma, Yu, Shu-Che, Stålhammar, Gustav, Crowston, Jonathan G., Tribble, James R., Swoboda, Peter, Williams, Pete A.·2025·Redox Biology
DOI 10.1016/j.redox.2025.103732PMC PMC12226095

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Abstract

Sarcopenia is the age-related degeneration of skeletal muscle, resulting in loss of skeletal muscle tone, mass, and quality. Skeletal muscle is a source of systemic metabolites and macromolecules important for neuronal health, function, and healthy neuronal aging. Age-related loss of skeletal muscle might result in decreased metabolite and macromolecule availability, resulting in reduced neuronal function or increased susceptibility to unhealthy aging and neurodegenerative diseases. We aimed to identify muscle metabolite candidates that regulate healthy aging. C57BL/6J mice were aged to young adult (4 months) and old age (25 months) and skeletal muscle was collected. Age-related muscle loss was confirmed by reduced muscle mass, muscle fiber degeneration, reduced myosin intensity, in addition to a metabolic shift and increased DNA damage in skeletal muscle. Using a low molecular weight enriched metabolomics protocol, we assessed the metabolic profile of skeletal muscle from young adult and old age mice and identified 20 metabolites that were significantly changed in aged muscle. These metabolite candidates were tested in C. elegans assays of lifespan, healthspan, muscle, and mitochondrial morphology under normal and stressed conditions. We identified four metabolite candidates (beta-alanine, 4-guanidinobutanoic acid, 4-hydroxyproline, pantothenic acid) that, when supplemented in C. elegans provided robust gero- and mitochondrial protection. These candidates also affected life-, and health- span in C. elegans models of amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Our findings support that aging muscle can be used to identify novel metabolite modulators of lifespan and health and may show promise for future treatments of neurodegenerative and neuromuscular disorders.

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Metadata

Authors
Jonk, S. M., Nicol, A., Chrysostomou, V., Lardner, E., Yu, S.-C., Stålhammar, G., Crowston, J. G., Tribble, J. R., Swoboda, P., & Williams, P. A.
Affiliations
  • Karolinska Institutet (SE)
  • National University of Singapore (SG)
  • The University of Sydney (AU)
Corresponding author
Williams, Pete A.
ORCID
Venue
Redox Biology
Publisher
Elsevier BV
Published
2025-09
Volume
85
Pages
103732
ISSN
2213-2317 (ISSN-L)
DOI
10.1016/j.redox.2025.103732
PMC
PMC12226095
OpenAlex
W4411302192
Cited by
6
References
2
Citations by year
2026: 4 · 2025: 2
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Redox Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • S:t Eriks Ögonforskningsstiftelse
  • Swedish Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Keywords
sarcopenia, skeletal muscle aging, muscle metabolomics, longevity, healthspan, beta-alanine, 4-hydroxyproline, pantothenic acid, mitochondrial protection, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, neurodegeneration, DNA damage
MeSH terms
Aging, Animals, Longevity, Mice, Inbred C57BL, Caenorhabditis elegans, Muscle, Skeletal, Mice, Metabolomics, Metabolome, Sarcopenia

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