Mouse exercise atlas maps how 8 weeks of running remodels 22 tissues, by sex and time of day
A Cell multi-omics study charts how chronic running reshapes 22 mouse tissues, revealing sex and circadian differences and cell-specific epigenetic changes in muscle.
Riepilogo
Exercise lowers all-cause mortality, but how it changes the body at the molecular level across organs, sexes, and times of day is poorly understood. Researchers gave mice 8 weeks of voluntary wheel running, then profiled 22 tissues and plasma in both active and inactive phases using RNA sequencing, metabolomics, proteomics, and single-nucleus RNA and DNA methylation sequencing. Skeletal muscle showed the largest transcriptional changes, including classic fiber-type switching. Most tissues changed more in the active phase, with exceptions in the hypothalamus, kidney, and lung. Females showed broader transcriptional responses. Single-nucleus methylation revealed cell-type-specific epigenetic remodeling that bulk methods miss, with a strong sex-biased response in muscle. Machine learning identified exercise signatures conserved across mammals. These are mouse findings, so human relevance remains to be tested.
Riepilogo Dettagliato
Regular exercise is among the most reliable interventions for lowering all-cause mortality, yet the molecular details of how it benefits different organs, in males and females, and at different times of day remain incompletely mapped. Such a map could help explain exercise's systemic benefits and guide mimetics and personalized training.
The team gave mice 8 weeks of voluntary wheel running and collected 22 tissues plus plasma during both active and inactive phases. They applied bulk RNA sequencing, metabolomics, and proteomics, along with single-nucleus RNA and methylation sequencing, creating a multi-layered atlas of the chronic exercise response.
Exercise caused widespread, tissue-specific remodeling, with skeletal muscle showing the largest transcriptomic shifts, including canonical fiber-type switching. Most tissues responded more strongly during the active phase, except the hypothalamus, kidney, and lung. Females showed broader transcriptional responses, including distinct gene downregulation. Pairing single-nucleus methylomes with transcriptomes identified which cell types drive epigenetic remodeling, changes invisible to bulk analysis. In specific myonuclei, gene-body demethylation and increased transcription tracked with fiber-type switching. Partially methylated domains in muscle were characterized, and the methylation response to training was strong and sex-biased. Machine learning identified exercise signatures conserved across mammalian species.
The atlas is a resource for finding tissue-, sex-, and time-of-day-specific exercise mechanisms, and it hints that timing and sex may matter for exercise prescription and biomarker development.
Caveats: this is based on the abstract only. The work was done in mice using voluntary running, so effect sizes, sample sizes, and direct human applicability are unclear. Findings are descriptive and associative, and the abstract does not report functional validation or health outcomes such as lifespan.
Risultati Principali
- Eight weeks of voluntary wheel running remodeled gene expression across 22 mouse tissues, with skeletal muscle showing the largest transcriptomic changes.
- Most tissues changed more during the active phase; hypothalamus, kidney, and lung were the exceptions.
- Females showed broader transcriptional responses to exercise than males, including distinct gene downregulation.
- Single-nucleus methylomes revealed cell-type-specific epigenetic remodeling, including gene-body demethylation tracking fiber-type switching in specific myonuclei.
- Machine learning identified exercise signatures conserved across mammalian species.
Metodologia
Mice underwent 8 weeks of voluntary wheel running; 22 tissues and plasma were collected in active and inactive circadian phases. Analyses included bulk RNA-seq, metabolomics, proteomics, and single-nucleus RNA and methylation sequencing, plus machine learning to identify cross-species exercise signatures.
Limitazioni dello Studio
Findings come from mice and an abstract-only review, so sample sizes, statistics, and validation are not assessed. Voluntary wheel running differs from human training, and the work is descriptive, without demonstrated links to lifespan or disease outcomes. Cross-species conservation was inferred computationally.
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