Serum metabolomics reveals signatures associated with physical resilience trajectories from middle to older age
- 1Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States / Department of Nutritional Sciences, Th
Abstract
Lifecourse physical resilience is defined by the ability to maintain abilities across multiple domains of physical performance. While the importance of physical resilience in functional independence and mobility disability is clear, studies investigating metabolomic signatures of physical resilience are lacking. Here, we performed untargeted metabolomics on serum samples from a community-based cohort of 237 individuals followed over 28 years, and applied spectral data mining tools to map identified metabolites to health phenotypes from public repositories. We identified metabolites across multiple chemical classes, including acylcarnitines, glutamine conjugates, and phosphocholines, that were differentially associated with physical resilience status. Notably, medium-chain acylcarnitines negatively associated with physical resilience were more frequently observed in disease phenotypes than in healthy individuals. Kynurenine, a tryptophan metabolite linked to age-related functional decline, increased more steeply with age in individuals with low physical resilience. We also found that metabolites of the antihypertensive drug verapamil were associated with physical resilience in a metabolism-dependent manner, differing between oxidative and glucuronidated forms. Together, these metabolic signatures offer a resource for identifying biochemical pathways and biomarkers relevant to physical resilience for healthy aging.
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BibTeX
@misc{seo2026serum,
title = {{Serum metabolomics reveals signatures associated with physical resilience trajectories from middle to older age}},
author = {J. I. Seo and T. A. W. Scheurink and C. X. Wang and K. E. Kvitne and W. D. G. Nunes and J. Zemlin and J. Bergstrom and P. C. Dorrestein and I. Mohanty and A. J. A. Molina},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751497},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751497v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Serum metabolomics reveals signatures associated with physical resilience trajectories from middle to older age
AU - J. I. Seo
AU - T. A. W. Scheurink
AU - C. X. Wang
AU - K. E. Kvitne
AU - W. D. G. Nunes
AU - J. Zemlin
AU - J. Bergstrom
AU - P. C. Dorrestein
AU - I. Mohanty
AU - A. J. A. Molina
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751497
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751497v1
AB - Lifecourse physical resilience is defined by the ability to maintain abilities across multiple domains of physical performance. While the importance of physical resilience in functional independence and mobility disability is clear, studies investigating metabolomic signatures of physical resilience are lacking. Here, we performed untargeted metabolomics on serum samples from a community-based cohort of 237 individuals followed over 28 years, and applied spectral data mining tools to map identified metabolites to health phenotypes from public repositories. We identified metabolites across multiple chemical classes, including acylcarnitines, glutamine conjugates, and phosphocholines, that were differentially associated with physical resilience status. Notably, medium-chain acylcarnitines negatively associated with physical resilience were more frequently observed in disease phenotypes than in healthy individuals. Kynurenine, a tryptophan metabolite linked to age-related functional decline, increased more steeply with age in individuals with low physical resilience. We also found that metabolites of the antihypertensive drug verapamil were associated with physical resilience in a metabolism-dependent manner, differing between oxidative and glucuronidated forms. Together, these metabolic signatures offer a resource for identifying biochemical pathways and biomarkers relevant to physical resilience for healthy aging.
ER -