Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults
Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults
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.
Ageing muscle metabolism, Muscle hypertrophy, Resistance training
Lim, Changhyun
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Lixandrão, Manoel
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Trivedi, Dakshat
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Xu, Yun
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Prokopidis, Konstantinos
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Roschel, Hamilton
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Phillips, Stuart M.
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Muhamadali, Howbeer
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Isanejad, Masoud
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Lim, Changhyun
159aaaa4-391f-4ec3-b3db-b7f739a61218
Lixandrão, Manoel
1e9c5002-cd37-4976-8318-ce7737aed1c4
Trivedi, Dakshat
0306079b-4ce0-468f-85ff-181aecca2619
Xu, Yun
7434b08c-2e13-476a-8902-b352a6ba8d1c
Prokopidis, Konstantinos
31f1f079-d93c-4ecd-9de6-df7759180fd8
Roschel, Hamilton
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Phillips, Stuart M.
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Muhamadali, Howbeer
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Isanejad, Masoud
4474352e-f563-4178-9811-426781dac7db
Lim, Changhyun, Lixandrão, Manoel, Trivedi, Dakshat, Xu, Yun, Prokopidis, Konstantinos, Roschel, Hamilton, Phillips, Stuart M., Muhamadali, Howbeer and Isanejad, Masoud
(2026)
Skeletal muscle metabolomic markers underlying the enhanced exercise-induced hypertrophy response to resistance training in older adults.
GeroScience.
(doi:10.1007/s11357-025-02074-x).
Abstract
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.
Text
s11357-025-02074-x
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Accepted/In Press date: 17 December 2025
e-pub ahead of print date: 5 January 2026
Keywords:
Ageing muscle metabolism, Muscle hypertrophy, Resistance training
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Local EPrints ID: 508713
URI: http://eprints.soton.ac.uk/id/eprint/508713
ISSN: 2509-2723
PURE UUID: e844847d-f055-4997-b7dc-44de9370bcd8
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Date deposited: 30 Jan 2026 17:50
Last modified: 31 Jan 2026 08:19
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Author:
Changhyun Lim
Author:
Manoel Lixandrão
Author:
Dakshat Trivedi
Author:
Yun Xu
Author:
Konstantinos Prokopidis
Author:
Hamilton Roschel
Author:
Stuart M. Phillips
Author:
Howbeer Muhamadali
Author:
Masoud Isanejad
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