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Delayed molecular aging, preservation of energy metabolism and enhanced exercise response in exercise-trained human muscle

GSE330697 Homo sapiens Expression profiling by high throughput sequencing 93 samples Submitted 2026/06/16 Platform GPL24676
Summary
Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address this, we performed transcriptomics, lipidomics, and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of sub-maximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy metabolism compared to young adults with comparable activity levels. Here we show that in trained older adults, 50% of these age-related differences were absent, resulting in profiles resembling those of young adults. While all participants displayed transcriptional immune and stress responses upon acute exercise, the magnitude of these responses in older adults correlated positively with their physical fitness. Integrated multi-omic analyses further revealed links between mitochondrial respiration, lipid metabolism, stress responses and NAD⁺ biology. These findings demonstrate that sustained physical training transforms age-related molecular profiles and provides a molecular atlas for studying fitness-dependent aging mechanisms.
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Direct links to NCBI, no account and no request form: the whole study as GSE330697_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 93 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1465274. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

Read from the first 40 of 93 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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