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Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years


Werdyani, S and Aitken, D and Gao, Z and Liu, M and Randell, EW and Rahman, P and Jones, G and Zhai, G, Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years, Skeletal Muscle, 12, (1) pp. 1-15. ISSN 2044-5040 (2022) [Refereed Article]


Copyright Statement

The Author(s) 2022. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1186/s13395-022-00286-9


Background: Skeletal muscles are essential components of the neuromuscular skeletal system that have an integral role in the structure and function of the synovial joints which are often affected by osteoarthritis (OA). The aim of this study was to identify the baseline metabolomic signatures for the longitudinal reduction of muscle strength over 10 years in the well-established community-based Tasmanian Older Adult Cohort (TASOAC).

Methods: Study participants were 50-79 year old individuals from the TASOAC. Hand grip, knee extension, and leg strength were measured at baseline, 2.6-, 5-, and 10-year follow-up points. Fasting serum samples were collected at 2.6-year follow-up point, and metabolomic profiling was performed using the TMIC Prime Metabolomics Profiling Assay. Generalized linear mixed effects model was used to identify metabolites that were associated with the reduction in muscle strength over 10 years after controlling for age, sex, and BMI. Significance level was defined at α=0.0004 after correction of multiple testing of 129 metabolites with Bonferroni method. Further, a genome-wide association study (GWAS) analysis was performed to explore if genetic factors account for the association between the identified metabolomic markers and the longitudinal reduction of muscle strength over 10 years.

Results: A total of 409 older adults (50% of them females) were included. The mean age was 60.936.50 years, and mean BMI was 27.124.18 kg/m2 at baseline. Muscle strength declined by 0.09 psi, 0.02 kg, and 2.57 kg per year for hand grip, knee extension, and leg strength, respectively. Among the 143 metabolites measured, 129 passed the quality checks and were included in the analysis. We found that the elevated blood level of asymmetric dimethylarginine (ADMA) was associated with the reduction in hand grip (p=0.0003) and knee extension strength (p=0.008) over 10 years. GWAS analysis found that a SNP rs1125718 adjacent to WISP1gene was associated with ADMA levels (p=4.39*10-8). Further, we found that the increased serum concentration of uric acid was significantly associated with the decline in leg strength over 10 years (p=0.0001).

Conclusion: Our results demonstrated that elevated serum ADMA and uric acid at baseline were associated with age-dependent muscle strength reduction. They might be novel targets to prevent muscle strength loss over time.

Item Details

Item Type:Refereed Article
Keywords:asymmetric dimethylarginine, biomarkers, hand grip, knee extension, leg muscle strength, metabolomics, muscle strength reduction, uric acid
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Aged health care
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Determinants of health
UTAS Author:Aitken, D (Associate Professor Dawn Aitken)
UTAS Author:Jones, G (Professor Graeme Jones)
ID Code:154032
Year Published:2022
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-10-25
Last Modified:2022-11-09
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