{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:46:46Z","timestamp":1785415606841,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,17]]},"group-title":"Cell Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01AG063801"],"award-info":[{"award-number":["R01AG063801"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA211963"],"award-info":[{"award-number":["R01CA211963"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AG013319"],"award-info":[{"award-number":["P30AG013319"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK121831"],"award-info":[{"award-number":["R01DK121831"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ocala Royal Dames for Cancer Research, US"},{"name":"American Cancer Society, US"},{"name":"Dr. Nihal Tumer Junior Faculty Research Catalyst Award, US"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Aging of the hematopoietic system impairs hematopoietic stem cell (HSC) function and alters bone marrow niche behavior, increasing susceptibility to anemia, infections, and hematologic malignancies. Here, pharmacologic clearance of senescent cells with the PROTAC compound 753b simultaneously targeting BCL-xL and BCL-2 reverses key secretory, transcriptional, and functional hallmarks of hematopoietic aging with low toxicity, restoring balanced lineage output. Single-cell RNA sequencing further demonstrates that 753b treatment attenuates aging-associated transcriptional signatures in HSCs, while selectively eliminating senescent, pro-survival niche cells without grossly perturbing niche composition. Functionally, 753b suppresses pro-inflammatory cues from both niche and hematopoietic cells including those emanating from neutrophil progenitors, rebalancing global bone marrow secretory ecosystem across stromal and hematopoietic compartments. Collectively, we identify 753b-induced senescent cell clearance as a powerful strategy to rejuvenate aged hematopoiesis and re-establish homeostatic communication between HSCs and their microenvironment, with implications for mitigating age-related hematologic dysfunction and improving hematologic health in older individuals.<\/jats:p>","DOI":"10.64898\/2026.07.16.736849","type":"posted-content","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:55:13Z","timestamp":1784296513000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting cellular senescence alleviates bone marrow aging"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-6763","authenticated-orcid":false,"given":"Bowen","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA"},{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Translational Tissue Engineering Center, Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason O.","family":"Brant","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"},{"name":"Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Neui","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Center for Musculoskeletal Disease Research and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Almeida","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Center for Musculoskeletal Disease Research and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhjot","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Demaria","sequence":"additional","affiliation":[{"name":"University of Groningen (RUG), European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen (UMCG), Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyanee","family":"Shirlekar","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Elisseeff","sequence":"additional","affiliation":[{"name":"Translational Tissue Engineering Center, Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangrong","family":"Zheng","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"},{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-6461","authenticated-orcid":false,"given":"Daohong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-8466","authenticated-orcid":false,"given":"Olga A.","family":"Guryanova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA"},{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072103500832000_2026.07.16.736849v1.1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1474"},{"key":"2026072103500832000_2026.07.16.736849v1.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017933"},{"key":"2026072103500832000_2026.07.16.736849v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2026.105425"},{"key":"2026072103500832000_2026.07.16.736849v1.4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007033"},{"key":"2026072103500832000_2026.07.16.736849v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37783-4"},{"key":"2026072103500832000_2026.07.16.736849v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70256"},{"key":"2026072103500832000_2026.07.16.736849v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01053-0"},{"key":"2026072103500832000_2026.07.16.736849v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.06.012"},{"key":"2026072103500832000_2026.07.16.736849v1.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024275"},{"key":"2026072103500832000_2026.07.16.736849v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2023.102284"},{"key":"2026072103500832000_2026.07.16.736849v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00738-8"},{"key":"2026072103500832000_2026.07.16.736849v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03547-7"},{"key":"2026072103500832000_2026.07.16.736849v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.012"},{"key":"2026072103500832000_2026.07.16.736849v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"2026072103500832000_2026.07.16.736849v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"2026072103500832000_2026.07.16.736849v1.16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-050120-105018"},{"key":"2026072103500832000_2026.07.16.736849v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4010"},{"key":"2026072103500832000_2026.07.16.736849v1.18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158450"},{"key":"2026072103500832000_2026.07.16.736849v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25453-2"},{"key":"2026072103500832000_2026.07.16.736849v1.20","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12344"},{"key":"2026072103500832000_2026.07.16.736849v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y"},{"key":"2026072103500832000_2026.07.16.736849v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00964-5"},{"key":"2026072103500832000_2026.07.16.736849v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11190"},{"key":"2026072103500832000_2026.07.16.736849v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12445"},{"key":"2026072103500832000_2026.07.16.736849v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"2026072103500832000_2026.07.16.736849v1.26","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014304"},{"key":"2026072103500832000_2026.07.16.736849v1.27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207591"},{"key":"2026072103500832000_2026.07.16.736849v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70261-8"},{"key":"2026072103500832000_2026.07.16.736849v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27210-x"},{"key":"2026072103500832000_2026.07.16.736849v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00811-7"},{"key":"2026072103500832000_2026.07.16.736849v1.31","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.281915"},{"key":"2026072103500832000_2026.07.16.736849v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y"},{"key":"2026072103500832000_2026.07.16.736849v1.33","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-021-00955-z"},{"key":"2026072103500832000_2026.07.16.736849v1.34","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009729"},{"key":"2026072103500832000_2026.07.16.736849v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00908-z"},{"key":"2026072103500832000_2026.07.16.736849v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0030-x"},{"key":"2026072103500832000_2026.07.16.736849v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"2026072103500832000_2026.07.16.736849v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.01.016"},{"key":"2026072103500832000_2026.07.16.736849v1.39","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ads1556"},{"key":"2026072103500832000_2026.07.16.736849v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"2026072103500832000_2026.07.16.736849v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2021.02.002"},{"key":"2026072103500832000_2026.07.16.736849v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.05.019"},{"key":"2026072103500832000_2026.07.16.736849v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2023.111888"},{"key":"2026072103500832000_2026.07.16.736849v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-024-00138-4"},{"key":"2026072103500832000_2026.07.16.736849v1.45","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101202"},{"key":"2026072103500832000_2026.07.16.736849v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00560-5"},{"key":"2026072103500832000_2026.07.16.736849v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2403-9"},{"key":"2026072103500832000_2026.07.16.736849v1.48","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add1951"},{"key":"2026072103500832000_2026.07.16.736849v1.49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1701655"},{"key":"2026072103500832000_2026.07.16.736849v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.03.017"},{"key":"2026072103500832000_2026.07.16.736849v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.040"},{"key":"2026072103500832000_2026.07.16.736849v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.031"},{"key":"2026072103500832000_2026.07.16.736849v1.53","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.622519"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.16.736849","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:50:16Z","timestamp":1784631016000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.16.736849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":53,"URL":"https:\/\/doi.org\/10.64898\/2026.07.16.736849","relation":{},"subject":[],"published":{"date-parts":[[2026,7,17]]},"subtype":"preprint"}}