{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T08:42:20Z","timestamp":1786178540748,"version":"build-2736575974"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Hangzhou Youth Innovation Team Project","award":["TD2023020"],"award-info":[{"award-number":["TD2023020"]}]},{"name":"Jinhua City Science and Technology Project","award":["2024-3-144"],"award-info":[{"award-number":["2024-3-144"]}]},{"name":"the Pioneer\" and \"Leading Goose\" R&D Program of Zhejiang","award":["2026C02A1147"],"award-info":[{"award-number":["2026C02A1147"]}]},{"name":"Medical and Health Science Program of Zhejiang Province","award":["2025KY1772"],"award-info":[{"award-number":["2025KY1772"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82301746"],"award-info":[{"award-number":["82301746"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82401816"],"award-info":[{"award-number":["82401816"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Key R&D Program of China","award":["2021YFA1102800"],"award-info":[{"award-number":["2021YFA1102800"]}]},{"name":"the National Key R&D Program of China","award":["2024YFA0918701"],"award-info":[{"award-number":["2024YFA0918701"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Aging-related functional decline in hematopoietic stem cells (HSCs) is closely associated with mitochondrial dysfunction and impaired mitophagy. This study aimed to investigate whether targeted restoration of mitophagy\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the myeloid cell leukemia 1 (MCL-1)\/light chain 3A pathway could rejuvenate aged HSCs and improve their regenerative capacity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified MCL-1 as the most highly expressed mitophagy receptor in aged HSCs. Treatment with UMI-77, a selective MCL-1 agonist, significantly enhanced mitophagy, reduced mitochondrial mass, improved mitochondrial membrane potential, and reduced reactive oxygen species levels in aged HSCs both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      . Single-cell RNA sequencing revealed that UMI-77 upregulated mitophagy-related genes (\n                      <jats:italic toggle=\"yes\">Sqstm1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Fundc1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Bnip3<\/jats:italic>\n                      ) and restored stemness signatures in long-term HSCs. Transplantation assays demonstrated that UMI-77-treated aged HSCs exhibited superior hematopoietic reconstitution capacity compared with those from control mice. However, this intervention also increased the proportion of myeloid-biased CD150\n                      <jats:sup>high<\/jats:sup>\n                      HSCs, a hallmark of aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Targeted mitophagy restoration\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      MCL-1 activation improves mitochondrial fitness and stemness in aged HSCs but does not reverse myeloid bias. These findings highlight mitophagy enhancement as a viable therapeutic approach, while suggesting combinatorial strategies may be needed to fully restore lineage balance in aging hematopoiesis.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      00, 000\u2013000.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261475098","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T02:03:52Z","timestamp":1785981832000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Restoration of Mitophagy Reinvigorates Aged Hematopoietic Stem Cells"],"prefix":"10.1177","author":[{"given":"Jin","family":"Liu","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Department of Cardiology, The Third People's Hospital of Deqing, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."},{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Department of Cardiology, The Third People's Hospital of Deqing, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Ling","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Department of Cardiology, The Third People's Hospital of Deqing, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liquan","family":"Hong","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Department of Cardiology, The Third People's Hospital of Deqing, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Department of Cardiology, The Third People's Hospital of Deqing, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."},{"name":"Department of Cardiology, Hangzhou Institute of Cardiovascular Diseases, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China."},{"name":"Hangzhou Lin\u2019an Fourth People\u2019s Hospital, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Chen","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpin","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Ju","sequence":"additional","affiliation":[{"name":"Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongguang","family":"Xia","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital &amp; 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