Untargeted Metabolomics Reveals Effects of Calorie Restriction on Skeletal Muscle in Older Female and Male Rats

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ID: 315566
2026
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Abstract
This study used untargeted metabolomics to investigate how calorie restriction (CR) affects skeletal muscle in older female and male rats. Fischer-344 Brown Norway rats of both sexes (22-23-months-old) were randomly assigned to an ad libitum-fed (AL) group or a CR group, which received 65% of the daily food intake of their sex-matched AL counterparts for eight-weeks. Epitrochlearis muscles were collected and analysed using untargeted metabolomics and immunoblotting. CR altered the abundance of 554 out of the 999 detected muscle metabolites. Additionally, 521 metabolites differed between females and males. CR raised the levels of metabolites related to bile acids, with significantly greater CR-induced elevation of secondary bile acids in females, suggesting possible sex-dependent interactions involving the gut, liver, and muscle. Furthermore, CR increased the levels of five glycolytic metabolites. These changes occurred without increases in the abundance of phosphofructokinase (a rate-limiting glycolytic enzyme) or in key allosteric activators (AMP and ADP). There was no evidence for a CR-induced increase in NAD+/NADH ratio: NAD+ levels decreased and NADH levels increased for CR versus AL rats. Approximately 78% of dipeptides were lower in CR rats compared to AL rats, and 38% of dipeptides were greater for females versus males. Levels for 5-methyl-2'-deoxycytidine (a methylated DNA breakdown product and potential marker for changes in DNA remodelling) were significantly reduced by CR only in females. Together, these findings offer important insights for understanding both the shared and sex-specific mechanisms through which CR influences muscle metabolism, health, and function.
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openalex_W7163130451 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Haiyan Wang, Jiwei Hao, Gregory D. Cartee
Journal the journals of gerontology series a, biological sciences and medical sciences
Year 2026
DOI
10.1093/gerona/glag144
URL
https://doi.org/10.1093/gerona/glag144
Keywords Keywords not found

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