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Metabolomic characterization of vigor to frailty among community-dwelling older Black and White men and women

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Abstract

Older women and Black individuals are more likely to experience frailty. A metabolomic characterization of frailty may help inform more effective interventions aimed at improving health, reducing disparities, and preventing frailty with aging. We sought to identify metabolites and pathways associated with vigor to frailty and determine whether associations differed by sex and/or race among n = 2189 older Black and White men and women from the Health, Aging, and Body Composition (Health ABC) study. Fasting plasma metabolites were measured using liquid chromatography-mass spectrometry. Vigor to frailty was based on weight change, physical activity, gait speed, grip strength, and usual energy. We used linear regression of a single metabolite on vigor to frailty, adjusting for age, sex, race, study site, and multiple comparisons using a Bonferroni correction. Among 500 metabolites, 113 were associated with vigor to frailty (p < 0.0001). Associations between metabolites and vigor to frailty did not differ significantly by race and/or sex. Lower amino acids, glycerophospholipids, sphingolipids, and dehydroepiandrosterone sulfate and higher acylcarnitines, fatty acids, amino acid derivatives, organic acids, carbohydrates, citric acid cycle metabolites, and trimethylamine oxide were associated with frailer scores. Pathway analyses identified the citric acid cycle as containing more frailty-associated metabolites than expected by chance (p = 0.00005). Calories and protein intake did not differ by vigor to frailty. Frailer Health ABC participants may have lower utilization of energy pathways, potentially as a result of less demand and less efficient utilization of similar amounts of nutrients when compared to more vigorous participants.

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Funding

This work was supported by National Institute on Aging Contracts N01-AG-6–2101, N01-AG-6–2103, and N01-AG-6–2106; National Institute on Aging Grant R01-AG-028050; and National Institute of Nursing Research Grant R01-NR-012459. This work was also supported in part by the Intramural Research Program of the National Institute on Aging. Metabolomics in the Health ABC study were supported by National Institute on Aging Grant R01-AG059729. Dr. Marron is supported by National Institute on Aging Career Development Award K01-AG-075143. Drs. Murthy and Shah are supported in part by grants from the National Institute on Aging (R01 AG059729); National Heart, Lung and Blood Institute (R01 HL136685); and an American Heart Association Strategically Focused Research Network grant in Cardiometabolic Disease.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Megan M. Marron, Shanshan Yao & Anne B. Newman

  2. Vanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, TN, USA

    Ravi V. Shah

  3. Division of Cardiovascular Medicine, Department of Medicine, and Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA

    Venkatesh L. Murthy

  4. Departments of Medicine and Clinical and Translational Science, University of Pittsburgh, Pittsburgh, PA, USA

    Anne B. Newman

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  1. Megan M. Marron
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  2. Shanshan Yao
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  4. Venkatesh L. Murthy
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  5. Anne B. Newman
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Correspondence to Megan M. Marron.

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Competing interests

Dr. Murthy owns stock or stock options in General Electric, Cardinal Health, Ionetix, Boston Scientific, Merck, Eli Lilly, Johnson and Johnson, and Pfizer. He has received research grants and consulting fees from Siemens Medical Imaging. He has served on medical advisory boards for Ionetix. Dr. Shah serves as a consultant for Amgen. Dr. Shah is a co-inventor on a patent for ex-RNA signatures of cardiac remodeling. There are no disclosures from the other authors.

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Marron, M.M., Yao, S., Shah, R.V. et al. Metabolomic characterization of vigor to frailty among community-dwelling older Black and White men and women. GeroScience 46, 2371–2389 (2024). https://doi.org/10.1007/s11357-023-01005-y

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  • DOI: https://doi.org/10.1007/s11357-023-01005-y

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