{"doi":"10.1111/acel.13467","title":"Late‐in‐life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts","abstract":"Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice. As expected, 24-month-old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8-month-old (adult) mice (all p < 0.05). To investigate the influence of late-in-life exercise training, additional cohorts of 21-month-old mice did (old-ETR) or did not (old-SED) complete a 3-month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old-ETR vs. old-SED mice at 24 months (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old-ETR vs. old-SED mice. These data provide the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts.","journal":"Aging Cell","year":2021,"id":169527,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":700534,"name":"Seul‐Ki Park","orcid":"0000-0001-7027-7679","position":1,"is_corresponding":false},{"id":355394,"name":"Rajeshwary Ghosh","orcid":"0000-0002-6576-4242","position":2,"is_corresponding":false},{"id":701307,"name":"Kellsey Ly","orcid":null,"position":3,"is_corresponding":false},{"id":701308,"name":"Caroline Ramous","orcid":null,"position":4,"is_corresponding":false},{"id":700535,"name":"Lauren Thompson","orcid":"0000-0001-8113-178X","position":5,"is_corresponding":false},{"id":701309,"name":"Michele Hansen","orcid":null,"position":6,"is_corresponding":false},{"id":700536,"name":"Maria Sara de Lima Coutinho Mattera","orcid":"0000-0003-2288-708X","position":7,"is_corresponding":false},{"id":502654,"name":"Karla Maria Pereira Pires","orcid":"0000-0002-5974-0279","position":8,"is_corresponding":false},{"id":700537,"name":"Maroua Ferhat","orcid":"0000-0002-1298-4620","position":9,"is_corresponding":false},{"id":700538,"name":"Sohom Mookherjee","orcid":"0000-0003-2785-1801","position":10,"is_corresponding":false},{"id":342493,"name":"Kevin J. Whitehead","orcid":"0000-0003-0419-7309","position":11,"is_corresponding":false},{"id":701310,"name":"Kandis Carter","orcid":null,"position":12,"is_corresponding":false},{"id":701311,"name":"Márcio Buffolo","orcid":null,"position":13,"is_corresponding":false},{"id":355396,"name":"Sihem Boudina","orcid":"0000-0002-4711-1109","position":14,"is_corresponding":false},{"id":355395,"name":"J. David Symons","orcid":"0000-0003-2021-4770","position":15,"is_corresponding":false},{"id":700533,"name":"Jae Min Cho","orcid":"0000-0002-4461-6945","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:46:15.560174Z","pmid":"34554626","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":[]}