Novel metabolomics markers are associated with pre-clinical decline in hand grip strength in community-dwelling older adults.
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2021-01
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Abstract
Background
Hand grip strength (HGS) has been proposed as a robust predictor for frailty and sarcopenia. Hence, identifying biomarkers for declining HGS accompanying aging could deepen our understanding of the biological underpinnings, informing pre-emptive intervention. Acylcarnitines (ACs) are metabolites generated by fatty acid metabolism in the mitochondria and are dysregulated in multiple disorders affecting the musculature. However, they have not been comprehensively profiled and examined regarding their utility in predicting variability in declining HGS, longitudinally. Thus, we aimed to: 1) validate previous findings on insignificant cross-sectional association between ACs and HGS, and 2) examine whether baseline ACs were associated with both decline and variability in HGS over 18 months, in community-dwelling older adults.Methods
We included participants who had HGS measured with dynamometer longitudinally (N = 121). We quantified ACs by targeted plasma metabolomics profiling. Multivariable linear regressions were then performed.Results
Cross-sectionally, ACs were not significantly associated with HGS. Longitudinally, baseline short-chain dicarboxylic and hydroxylated acylcarnitines (AC-DC/-OH) levels were inversely associated with and significantly explained the variability in 18-month decline in HGS. A specific AC species, the C4-OH, accounted for most of the variance explained.Conclusions
We showed novel biomarkers for declining HGS, furthering molecular understanding and informing nutritional pre-emptive programs.Type
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Ng, Ted Kheng Siang, Jean-Paul Kovalik, Jianhong Ching, Angelique W Chan and David Bruce Matchar (2021). Novel metabolomics markers are associated with pre-clinical decline in hand grip strength in community-dwelling older adults. Mechanisms of ageing and development, 193. p. 111405. 10.1016/j.mad.2020.111405 Retrieved from https://hdl.handle.net/10161/22764.
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Scholars@Duke
David Bruce Matchar
My research relates to clinical practice improvement - from the development of clinical policies to their implementation in real world clinical settings. Most recently my major content focus has been cerebrovascular disease. Other major clinical areas in which I work include the range of disabling neurological conditions, cardiovascular disease, and cancer prevention.
Notable features of my work are: (1) reliance on analytic strategies such as meta-analysis, simulation, decision analysis and cost-effectiveness analysis; (2) a balancing of methodological rigor the needs of medical professionals; and (3) dependence on interdisciplinary groups of experts.
This approach is best illustrated by the Stroke Prevention Patient Outcome Research Team (PORT), for which I served as principal investigator. Funded by the AHCPR, the PORT involved 35 investigators at 13 institutions. The Stroke PORT has been highly productive and has led to a stroke prevention project funded as a public/private partnership by the AHCPR and DuPont Pharma, the Managing Anticoagulation Services Trial (MAST). MAST is a practice improvement trial in 6 managed care organizations, focussing on optimizing anticoagulation for individuals with atrial fibrillation.
I serve as consultant in the general area of analytic strategies for clinical policy development, as well as for specific projects related to stroke (e.g., acute stroke treatment, management of atrial fibrillation, and use of carotid endarterectomy.) I have worked with AHCPR (now AHRQ), ACP, AHA, AAN, Robert Wood Johnson Foundation, NSA, WHO, and several pharmaceutical companies.
Key Words: clinical policy, disease management, stroke, decision analysis, clinical guidelines
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