ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Aging
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1655325
This article is part of the Research TopicDecoding Neurodegeneration: Insights into the Pathways of Neurological DeclineView all 3 articles
Comparative Analysis of Sex-Dependent Serum Metabolomic Patterns Across the Lifespan of Rhesus Macaques
Provisionally accepted
- 1Wisconsin National Primate Research Center, Madison, United States
- 2Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, United States
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Aging is accompanied by systemic metabolic changes that contribute to disease susceptibility and functional decline. Sex differences in aging have been reported in humans, yet their mechanistic basis remains poorly understood. Due to their physiological similarity to humans, rhesus macaques are a powerful translational model to investigate sex-specific metabolomic aging under controlled conditions. Methods: Targeted serum metabolomics were conducted in 58 rhesus (35 females, 23 males), ranging from 1.66 to 25.71 years of age, quantifying 513 metabolites spanning lipids, amino acids, and related compounds. Multivariate, univariate, and generalized additive model (GAM) analyses were performed to evaluate age-associated trajectories and test for sex differences. Results: Age-related changes in both sexes were identified in metabolites related to hormones (e.g. DHEAS), amino acid biosynthesis and catabolism (e.g. beta-alanine, sarcosine, t4-OH-pro), and energy metabolism (e.g. hexose). Sex affected age-related metabolic trajectories in lipids, amino acids and related compounds, and gut microbial species. Females demonstrated a profound increase in serum triglycerides (TGs), amino acids, and other small molecules, while males exhibited a heterogenous profile with changes in lipids, but no TGs were affected. Males also exhibited altered levels of amino acids and related metabolites, hormones, gut microbial metabolites, and energy-associated metabolites. Conclusions: These results highlight pronounced sex differences in metabolomic aging trajectories in rhesus macaques, particularly in lipid and amino acid metabolism. These findings underscore the importance of incorporating sex as a biological variable in aging studies and support the utility of rhesus macaques for identifying conserved, sex-specific biomarkers of biological aging.
Keywords: Metabolomics, age, rhesus macaques, Lipids, Amino Acids, sex differences
Received: 27 Jun 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Metzler, Goy, Metzger, Emborg and Kapoor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Amita Kapoor, Wisconsin National Primate Research Center, Madison, United States
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