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<p>Aging is accompanied by metabolic alterations that may precede or parallel functional decline. While chronological age correlates with numerous circulating metabolites, the extent to which these associations reflect age-independent functional deterioration remains unclear. To identify plasma metabolites associated with muscle quality (assessed by bioelectrical impedance phase angle at 50&#xa0;kHz) and pulmonary function (forced vital capacity, FVC) independently of chronological age, and to characterize the metabolic signatures shared across these functional domains. We analyzed 135 plasma metabolites using the Biocrates AbsoluteIDQ p180 kit in 72 community-dwelling adults (age range 20–85&#xa0;years) from the Balearic Islands Study of Aging (BILSA). Metabolite associations with age, muscle quality, and FVC were assessed using linear regression models. Functional outcomes were adjusted for age and sex to isolate age-independent associations. Participants were also stratified into sex-specific tertiles for visualization. Thirty metabolites were associated with chronological age (<i>p</i> &lt; 0.05), with seven remaining significant after false discovery rate (FDR) correction, including taurine, free carnitine (C0), glutamate, and long-chain acylcarnitine C18:1. For muscle quality, bivariate analysis identified 55 significant associations, but only 18 remained significant after age and sex adjustment, representing a 67% reduction attributable to age confounding. Similarly, FVC associations decreased from 41 in bivariate analysis to 3 after adjustment, with no FDR-significant metabolites. Among the age-adjusted associations with muscle quality, long-chain acylcarnitines C18:1 (β =  − 0.48, <i>p</i> = 0.002) and C14:1 (β =  − 0.47, <i>p</i> = 0.006) showed the strongest association. Eleven metabolites, mainly sphingomyelins (SM C16:0, SM C16:1, SM C18:1, SM C24:1, SM C26:1, SM(OH) C22:1, SM(OH) C22:2, SM(OH) C24:1), along with taurine, lysoPC a C18:2, and PC ae C30:2, were significant and shared across age, muscle quality and FVC. Most metabolite associations with functional aging markers were substantially attenuated after adjustment for chronological age, highlighting the strong confounding effect of aging on the circulating metabolome. Long-chain acylcarnitines (particularly C18:1 and C14:1) emerged as exploratory candidates for further investigation in relation to muscle quality and functional aging. Overall, these findings emphasize the importance of rigorous covariate adjustment in metabolomic studies of aging and support the need for longitudinal validation in larger independent cohorts.</p> Graphical abstract <p></p>

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Exploratory plasma metabolomics of aging-related associations with muscle quality and pulmonary function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • C. Navas-Enamorado,
  • X. Capo,
  • A. Sánchez-Polo,
  • S. Marín,
  • M. Cascante,
  • L. Masmiquel,
  • M. Torrens-Mas,
  • M. Gonzalez-Freire

摘要

Aging is accompanied by metabolic alterations that may precede or parallel functional decline. While chronological age correlates with numerous circulating metabolites, the extent to which these associations reflect age-independent functional deterioration remains unclear. To identify plasma metabolites associated with muscle quality (assessed by bioelectrical impedance phase angle at 50 kHz) and pulmonary function (forced vital capacity, FVC) independently of chronological age, and to characterize the metabolic signatures shared across these functional domains. We analyzed 135 plasma metabolites using the Biocrates AbsoluteIDQ p180 kit in 72 community-dwelling adults (age range 20–85 years) from the Balearic Islands Study of Aging (BILSA). Metabolite associations with age, muscle quality, and FVC were assessed using linear regression models. Functional outcomes were adjusted for age and sex to isolate age-independent associations. Participants were also stratified into sex-specific tertiles for visualization. Thirty metabolites were associated with chronological age (p < 0.05), with seven remaining significant after false discovery rate (FDR) correction, including taurine, free carnitine (C0), glutamate, and long-chain acylcarnitine C18:1. For muscle quality, bivariate analysis identified 55 significant associations, but only 18 remained significant after age and sex adjustment, representing a 67% reduction attributable to age confounding. Similarly, FVC associations decreased from 41 in bivariate analysis to 3 after adjustment, with no FDR-significant metabolites. Among the age-adjusted associations with muscle quality, long-chain acylcarnitines C18:1 (β =  − 0.48, p = 0.002) and C14:1 (β =  − 0.47, p = 0.006) showed the strongest association. Eleven metabolites, mainly sphingomyelins (SM C16:0, SM C16:1, SM C18:1, SM C24:1, SM C26:1, SM(OH) C22:1, SM(OH) C22:2, SM(OH) C24:1), along with taurine, lysoPC a C18:2, and PC ae C30:2, were significant and shared across age, muscle quality and FVC. Most metabolite associations with functional aging markers were substantially attenuated after adjustment for chronological age, highlighting the strong confounding effect of aging on the circulating metabolome. Long-chain acylcarnitines (particularly C18:1 and C14:1) emerged as exploratory candidates for further investigation in relation to muscle quality and functional aging. Overall, these findings emphasize the importance of rigorous covariate adjustment in metabolomic studies of aging and support the need for longitudinal validation in larger independent cohorts.

Graphical abstract