{"doi":"10.14814/phy2.70497","title":"Transcriptomic time course of skeletal muscle disuse and rehabilitation in middle‐aged adults","abstract":"Disuse drives rapid muscle atrophy and metabolic dysfunction. This study aimed to characterize phenotypic and transcriptomic skeletal muscle changes in middle-aged individuals during disuse and rehabilitation. Eleven healthy middle-aged adults (6 males, 5 females; age; 57 ± 5 years) underwent 7 days of unilateral lower limb suspension (ULLS). Following disuse, participants participated in a rehabilitation program consisting of either a lower-body resistance exercise (RE) or walking control (WC) three times weekly for 2 weeks. Bilateral skeletal muscle biopsies were collected at Day 0 and Day 7 of disuse and 2 h post-exercise on Days 7, 9, 11, and 21. Strength testing was conducted, and RNA sequencing was performed on muscle samples. Seven days of disuse reduced knee extension strength (14%; p < 0.05) and isometric force (13%; p < 0.05). Over-representation analysis revealed a downregulation of mRNAs related to cellular respiration and NADH dehydrogenase complex assembly. Resistance exercise induced robust, but different, transcriptional changes in both disuse- and control-legs. Walking had minimal effect on the muscle transcriptome. We conclude that 7 days of disuse reduced leg strength, decreased mitochondrial gene expression, and increased inflammation and apoptosis-related genes. We also conclude that resistance exercise enhanced recovery from disuse by improving strength, associated with significant transcriptomic changes.","journal":"Physiological Reports","year":2025,"id":524090,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9408,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1048111,"name":"Sean P. Kilroe","orcid":null,"position":1,"is_corresponding":false},{"id":1396969,"name":"Erik D. Marchant","orcid":"0000-0002-2222-7594","position":2,"is_corresponding":false},{"id":477671,"name":"Emily Arentson‐Lantz","orcid":"0000-0001-7303-8067","position":3,"is_corresponding":false},{"id":225076,"name":"Steven G. Widen","orcid":"0000-0002-6512-363X","position":4,"is_corresponding":false},{"id":691495,"name":"Jill C. Thompson","orcid":null,"position":5,"is_corresponding":false},{"id":370877,"name":"Alejandro Villasante‐Tezanos","orcid":"0000-0001-5108-8637","position":6,"is_corresponding":false},{"id":242036,"name":"Elena Volpi","orcid":"0000-0001-8776-0384","position":7,"is_corresponding":false},{"id":344877,"name":"Douglas Paddon‐Jones","orcid":"0000-0002-3762-5130","position":8,"is_corresponding":false},{"id":235357,"name":"Blake B. Rasmussen","orcid":"0000-0001-7854-5375","position":9,"is_corresponding":false},{"id":1048110,"name":"Zachary D. Von Ruff","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40771108","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}