{"doi":"10.3389/fphys.2025.1686942","title":"Chronic circadian misalignment accelerates sarcopenia progression in mice","abstract":"Introduction: In today's 24/7 society, circadian misalignment caused by environmental and lifestyle factors is associated with various adverse health consequences. Understanding tissue-specific pathology is required to counter this growing public health challenge. A potential association of environmental circadian misalignment with sarcopenia, or accelerated loss of skeletal muscle strength and mass, is poorly documented. Methods: 14-week-old wild-type C57BL/6J male mice were exposed to a chronic jet lag (CJL) paradigm consisting of an 8-h phase advance every 4 days (the ADV group) or a fixed light-dark cycle (the LD group) for 64 weeks. Grip strength was measured during the experiment, and hindlimb muscle weight was assessed after the 64-week CJL. In addition, transcriptomic and histological analysis of the hindlimb muscles were performed in all animals. Results: ADV mice exhibited significant reductions in grip strength and muscle weight relative to LD mice. Transcriptomic and histological analyses showed activation of TWEAK/Fn14 signaling and reduced myofiber cross-sectional area, hallmark features of sarcopenia, in the ADV group. Somewhat surprisingly, ADV mice showed increased centrally nucleated fibers, myosin heavy chain co-expressing fibers, and myogenic gene expression, suggesting that compensatory muscle regeneration and remodeling processes are activated but remain insufficient to counter muscle atrophy. Conclusion: These findings demonstrate that circadian misalignment is a potential risk factor for sarcopenia, underscoring circadian rhythms as a key regulator and actionable target for sarcopenia prevention.","journal":"Frontiers in Physiology","year":2025,"id":524835,"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":0.9362,"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":460025,"name":"Nobuya Koike","orcid":null,"position":1,"is_corresponding":false},{"id":356152,"name":"Naoki Okubo","orcid":"0000-0001-9405-8462","position":2,"is_corresponding":false},{"id":1277301,"name":"Yasuhiro Umemura","orcid":"0000-0003-3202-1124","position":3,"is_corresponding":false},{"id":1277303,"name":"Yoshiki Tsuchiya","orcid":"0000-0002-8962-5159","position":4,"is_corresponding":false},{"id":1277699,"name":"Kazuya Yabumoto","orcid":null,"position":5,"is_corresponding":false},{"id":1399543,"name":"Yasuhiro Endo","orcid":null,"position":6,"is_corresponding":false},{"id":1399544,"name":"K IINUMA","orcid":null,"position":7,"is_corresponding":false},{"id":1399545,"name":"Akiyo Kakibuchi","orcid":null,"position":8,"is_corresponding":false},{"id":1277304,"name":"Akira Sugimoto","orcid":"0000-0001-9055-8427","position":9,"is_corresponding":false},{"id":1398954,"name":"Kenji Takahashi","orcid":"0000-0002-6775-9850","position":10,"is_corresponding":false},{"id":484377,"name":"Seung‐Hee Yoo","orcid":"0000-0002-9930-560X","position":11,"is_corresponding":false},{"id":458445,"name":"Zheng Chen","orcid":"0000-0002-2464-5474","position":12,"is_corresponding":false},{"id":458444,"name":"Kazuhiro Yagita","orcid":"0000-0002-1889-7050","position":13,"is_corresponding":false},{"id":1277700,"name":"Takashi Seya","orcid":null,"position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41321491","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":[]}