{"doi":"10.20517/jca.2021.13","title":"Ser9 phosphorylation of GSK-3β promotes aging in the heart through suppression of autophagy","abstract":"INTRODUCTION: Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase and a negative regulator of cardiac hypertrophy. Phosphorylation of GSK-3β at Ser9 negatively regulates its kinase activity. The role of GSK-3β in cardiac aging remains poorly understood. AIM: The study aimed to elucidate the role of GSK-3β Ser9 phosphorylation in mediating cardiac aging and the underlying mechanism. METHODS AND RESULTS: reversed the age-associated decline in autophagy in the mouse heart. GSK-3β directly phosphorylates Ulk1, a regulator of autophagy, at Ser913, thereby stimulating autophagy in cardiomyocytes. Ulk1Ser913A KI mice exhibited decreased autophagic flux and increased senescence in cardiomyocytes. CONCLUSION: Our results suggest that GSK-3β is inactivated during aging through Ser9 phosphorylation, which in turn plays an important role in mediating cardiac aging. GSK-3β promotes autophagy through phosphorylation of Ulk1 at Ser913, which in turn prevents aging in the heart.","journal":"The Journal of Cardiovascular Aging","year":2021,"id":199354,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.966,"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":775805,"name":"Yasuhiro Maejima","orcid":"0000-0001-7450-4840","position":1,"is_corresponding":false},{"id":775806,"name":"Akihiro Shirakabe","orcid":"0000-0001-8894-3297","position":2,"is_corresponding":false},{"id":775807,"name":"Takanobu Yamamoto","orcid":"0000-0002-3355-9252","position":3,"is_corresponding":false},{"id":655709,"name":"Yoshiyuki Ikeda","orcid":"0000-0001-5452-1504","position":4,"is_corresponding":false},{"id":247599,"name":"Junichi Sadoshima","orcid":"0000-0003-3724-4132","position":5,"is_corresponding":false},{"id":259098,"name":"Peiyong Zhai","orcid":"0000-0002-6482-2033","position":6,"is_corresponding":false},{"id":775804,"name":"Yanbin Chen","orcid":"0000-0002-3334-8383","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"34778891","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":[]}