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

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 th...

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Autores principales: Werdyani, Salem, Aitken, Dawn, Gao, Zhiwei, Liu, Ming, Randell, Edward W., Rahman, Proton, Jones, Graeme, Zhai, Guangju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819943/
https://www.ncbi.nlm.nih.gov/pubmed/35130970
http://dx.doi.org/10.1186/s13395-022-00286-9
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author Werdyani, Salem
Aitken, Dawn
Gao, Zhiwei
Liu, Ming
Randell, Edward W.
Rahman, Proton
Jones, Graeme
Zhai, Guangju
author_facet Werdyani, Salem
Aitken, Dawn
Gao, Zhiwei
Liu, Ming
Randell, Edward W.
Rahman, Proton
Jones, Graeme
Zhai, Guangju
author_sort Werdyani, Salem
collection PubMed
description 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 60.93±6.50 years, and mean BMI was 27.12±4.18 kg/m(2) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13395-022-00286-9.
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spelling pubmed-88199432022-02-08 Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years Werdyani, Salem Aitken, Dawn Gao, Zhiwei Liu, Ming Randell, Edward W. Rahman, Proton Jones, Graeme Zhai, Guangju Skelet Muscle Research 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 60.93±6.50 years, and mean BMI was 27.12±4.18 kg/m(2) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13395-022-00286-9. BioMed Central 2022-02-07 /pmc/articles/PMC8819943/ /pubmed/35130970 http://dx.doi.org/10.1186/s13395-022-00286-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Werdyani, Salem
Aitken, Dawn
Gao, Zhiwei
Liu, Ming
Randell, Edward W.
Rahman, Proton
Jones, Graeme
Zhai, Guangju
Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title_full Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title_fullStr Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title_full_unstemmed Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title_short Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
title_sort metabolomic signatures for the longitudinal reduction of muscle strength over 10 years
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819943/
https://www.ncbi.nlm.nih.gov/pubmed/35130970
http://dx.doi.org/10.1186/s13395-022-00286-9
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