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Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults

Lookup NU author(s): Dr Changhyun LimORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2025. Resistance training (RT) is an effective intervention for improving muscle health and metabolism in ageing, but the degree of responsiveness (hypertrophy) to RT varies substantially. We examined muscle metabolomic profiles before and after 10-weeks RT in older adults classified into upper (UPPER) and lower (LOWER) tertiles of hypertrophy to identify key metabolic adaptation differences. Fifty older adults (23 males, 27 females, mean 68.2 years old) completed 10 weeks of RT combined with whey protein supplementation. Quadriceps cross-sectional area (CSA) was assessed via magnetic resonance imaging before and after RT. Participants were grouped into UPPER (n = 25, 10.3 ± 2% CSA increase) or LOWER (n = 25, 3.3 ± 2% CSA increase) based on ranked CSA changes. We profiled skeletal muscle tissues from the UPPER and LOWER groups using a metabolomics platform. Over 2,500 metabolites were mapped to 104 metabolic pathways. In the UPPER group, upregulation of tryptophan-indole metabolites and the kynurenine pathway suggests a potential role of gut function and anti-inflammatory effect on RT-induced hypertrophy. Also, leucine, isoleucine and valine were significantly upregulated in the absence of their catabolites. Enrichment of urea cycle/amino group metabolism alongside mitochondria-matrix metabolites in the UPPER group indicates improved amino acids and energy homeostasis. Our findings highlight distinct RT-induced skeletal muscle metabolic profiles between UPPER and LOWER in older adults, underscoring the value of metabolic data. These metabolic pathways are important for understanding what contributes to the heterogeneity of hypertrophic response to RT in older adults.


Publication metadata

Author(s): Lim C, Lixandrao M, Trivedi D, Xu Y, Prokopidis K, Roschel H, Phillips SM, Muhamadali H, Isanejad M

Publication type: Article

Publication status: Published

Journal: GeroScience

Year: 2026

Pages: Epub ahead of print

Online publication date: 05/01/2026

Acceptance date: 17/12/2025

Date deposited: 19/01/2026

ISSN (print): 2509-2715

ISSN (electronic): 2509-2723

Publisher: Springer Nature

URL: https://doi.org/10.1007/s11357-025-02074-x

DOI: 10.1007/s11357-025-02074-x

Data Access Statement: Most of the data supporting the findings of this study are available in the supplemental materials.

PubMed id: 41491333


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Funding

Funder referenceFunder name
Canada Research Chairs Program (CRC-2021–00495)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)—Process Numbers: 2016/22635–6 and 2018/15691–2
Liverpool Shared Research Facilities (LIV-SRF)
Natural Sciences and Engineering Research Council (NSERC) of Canada (RGPIN-2020–06346)
UKRI Biotechnology and Biological Sciences Research Council

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