Multi-Omics Atlas of Chronic Exercise [AcuteRW_RNAseq]

ABSTRACT: Regular exercise reduces all-cause mortality, yet its molecular effects across organs, sexes, and circadian phases remain incompletely understood. We subjected mice to 8-week voluntary wheel running and collected 22 tissues and plasma during the inactive and active phases, profiling bulk RNA sequencing, metabolomics, proteomics, and single-nucleus RNA and methylation sequencing. Exercise induced canonical fiber-type switching and widespread, tissue-specific remodeling, with the largest transcriptomic changes in skeletal muscle. Most tissues changed more during the active phase; kidney and lung, during the inactive phase. Females showed broader transcriptional responses, with distinct downregulation. Pairing single-nucleus methylomes with transcriptomes resolved, at single-cell and single-base resolution, which cell types drive exercise-induced epigenetic remodeling, unresolved by bulk studies: coordinated gene-body demethylation and transcription tracked fiber-type switching in specific myonuclei, and cell-type-resolved methylation—including partially methylated domains characterized in muscle for the first time—revealed a strong, sex-biased epigenetic training response. Machine learning identified conserved cross-mammalian exercise signatures.

ORGANISM(S): Mus musculus

PROVIDER: GSE344070 | GEO | 2026/10/15

REPOSITORIES: GEO