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Biomarkers associated with lower limb muscle function in individuals with sarcopenia: a systematic review

Jones, Rebecca; Paul, Lorna; Steultjens, Martijn; Smith, Stephanie Louise


Rebecca Jones

Lorna Paul

Martijn Steultjens


Lower limb muscle dysfunction is a key driver for impaired physical capacity and frailty status, both characteristics of sarcopenia. Sarcopenia is the key pathway between frailty and disability. Identifying biological markers for early diagnosis, treatment, and prevention may be key to early intervention and prevention of disability particularly mobility issues. To identify biological markers associated with lower limb muscle (dys)function in adults with sarcopenia, a systematic literature search was conducted in AMED, CINAHL, Cochrane Library, EMBASE, Medline, PubMed, Scopus, SPORTDiscus, and Web of Science databases from inception to 17 November 2021. Title, abstract, and full-text screening, data extraction, and methodological quality assessment were performed by two reviewers independently and verified by a third reviewer. Depending on available data, associations are reported as either Pearson's correlations, regression R2 or partial R2, P value, and sample size (n). Twenty eligible studies including 3306 participants were included (females: 79%, males: 15%, unreported: 6%; mean age ranged from 53 to 92years) with 36% in a distinct sarcopenic subgroup (females: 73%, males: 19%, unreported: 8%; mean age range 55–92years). A total of 119 biomarkers were reported, categorizedinto: genetic and microRNAs (n=64), oxidative stress (n=10), energy metabolism (n=18), inflammation (n=7), enzyme (n=4), hormone (n=7), bone (n=3), vitamin (n=2), and cytokine (n=4) markers) and seven lower limb muscle measures predominately focused on strength. Seven studies reported associations between lower limb muscle measures including (e.g. power, force, and torque) and biomarkers. In individuals with sarcopenia, muscle strength was positively associated with free testosterone (r=0.40, P=0.01; n=46). In analysis with combined sarcopenic and non-sarcopenic individuals, muscle strength was positively associated with combined genetic and methylation score (partial R2=0.122, P=0.03; n=48) and negatively associated with sarcopenia-driven methylation score (partial R2=0.401, P<0.01; n=48). Biomarkers related to genetics (R2=0.001–0.014, partial R2=0.013–0.122, P>0.05; n=48), oxidative stress (r=0.061, P>0.05; n≥77), hormone (r=0.01, ρ=0.052 p>0.05, n≥46) and combined protein, oxidative stress, muscle performance, and hormones (R2=22.0, P>0.05; n≥82) did not report significant associations with lower limb muscle strength. Several biomarkers demonstrated associations with lower limb muscle dysfunction. The current literature remains difficult to draw clear conclusions on the relationship between biomarkers and lower limb muscle dysfunction in adults with sarcopenia. Heterogeneity of biomarkers and lower limb muscle function precluded direct comparison. Use of international classification of sarcopenia and a set of core standardized outcome measures should be adopted to aid future investigation and recommendations to be made.


Jones, R., Paul, L., Steultjens, M., & Smith, S. L. (2022). Biomarkers associated with lower limb muscle function in individuals with sarcopenia: a systematic review. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2791-2806.

Journal Article Type Review
Acceptance Date Jul 4, 2022
Online Publication Date Aug 17, 2022
Publication Date 2022-12
Deposit Date Jul 5, 2022
Publicly Available Date Aug 17, 2022
Journal Journal of Cachexia, Sarcopenia and Muscle
Print ISSN 2190-5991
Electronic ISSN 2190-6009
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
Volume 13
Issue 6
Pages 2791-2806
Keywords Physiology (medical); Orthopedics and Sports Medicine
Public URL
Publisher URL


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