{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:44:25Z","timestamp":1792856665305,"version":"4.5.0"},"update-to":[{"DOI":"10.12688\/f1000research.151963.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000}}],"reference-count":50,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007338","name":"The Foundation for Barnes-Jewish Hospital","doi-asserted-by":"crossref","award":["6359"],"award-info":[{"award-number":["6359"]}],"id":[{"id":"10.13039\/100007338","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>Background Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD). Methods This single-center study will recruit 30 participants total aged 50 years or older with schizophrenia\/schizoaffective disorder or 60 years or older with TRD; the difference in age limits is because individuals with schizophrenia are biologically about 10 years older than general population owing to metabolic burden. Each participant will receive two consecutive days of 100 mg oral dasatinib plus 1250 mg oral quercetin at baseline and weeks one through three, (i.e., two days on, five days off ) along with lifestyle risk management education. Questionnaires and assessments will measure health and cognitive function as well as psychiatric function at baseline, week 10, and one year. Magnetic Resonance Imaging (MRI) will measure structural and functional brain health at baseline and 10 weeks. Blood sampling for SASP testing will occur at seven time points: baseline, weeks one through four, week 10, and one year. Conclusion This pilot aims to evaluate the safety and feasibility of the senolytic regimen and D+Q\u2019s potential to counteract accelerated aging in adults with schizophrenia\/schizoaffective disorder and TRD. Trial registration Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders is registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.<\/ns5:p>","DOI":"10.12688\/f1000research.151963.2","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T10:50:07Z","timestamp":1741171807000},"page":"1072","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib Plus Quercetin to mitigate age-related health and cognitive decline in mental disorders"],"prefix":"10.12688","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-4016","authenticated-orcid":false,"given":"Abigail","family":"Schweiger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breno","family":"Diniz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger","family":"Nicol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-6164","authenticated-orcid":false,"given":"Julie","family":"Schweiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andes E.","family":"Dasklakis-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"Lenze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20010737","article-title":"Subjective Overview of Accelerated Aging in Schizophrenia.","volume":"20","author":"M Seeman","year":"2022","journal-title":"Int J Environ Res Public Health."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"200-209","DOI":"10.1038\/s44220-023-00033-z","article-title":"Major depression, physical health and molecular senescence markers abnormalities.","volume":"1","author":"J Seitz-Holland","year":"2023\/03\/01 2023","journal-title":"Nat Mental Health."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"163-168","DOI":"10.1016\/j.jad.2024.05.071","article-title":"Elevated senescence-associated secretory phenotype index in late-life bipolar disorder.","volume":"360","author":"T Tessema","year":"2024","journal-title":"J Affect Disord."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1321-1322","DOI":"10.1001\/jama.2018.9562","article-title":"Aging as a Biological Target for Prevention and Therapy.","volume":"320","author":"N Barzilai","year":"2018","journal-title":"JAMA."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"542-544","DOI":"10.1016\/j.jagp.2019.11.009","article-title":"Mood Disorders and Dementia: Time for Action.","volume":"28","author":"B Diniz","year":"2020","journal-title":"Am J Geriatr Psychiatry."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1130-1138","DOI":"10.1056\/NEJMoa052619","article-title":"Maintenance treatment of major depression in old age.","volume":"354","author":"C Reynolds","year":"2006","journal-title":"N Engl J Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"210-218","DOI":"10.1111\/acel.12562","article-title":"Cellular senescence in osteoarthritis pathology.","volume":"16","author":"K McCulloch","year":"2017","journal-title":"Aging Cell."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1097-1105","DOI":"10.1016\/j.jagp.2018.07.005","article-title":"The Molecular Intersection Between Senescence and Major Depression in the Elderly.","volume":"26","author":"B Diniz","year":"2018","journal-title":"Am J Geriatr Psychiatry."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"958-978","DOI":"10.1038\/s41580-024-00727-x","article-title":"The senescence-associated secretory phenotype and its physiological and pathological implications.","volume":"25","author":"B Wang","year":"2024","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1090-1100","DOI":"10.1038\/s43587-022-00326-5","article-title":"NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health.","volume":"2","author":"C SenNet","year":"2022","journal-title":"Nat Aging."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"99-118","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression.","volume":"5","author":"J Coppe","year":"2010","journal-title":"Annu Rev Pathol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"121-133","DOI":"10.1016\/j.bone.2019.01.015","article-title":"Cellular senescence in bone.","volume":"121","author":"J Farr","year":"2019","journal-title":"Bone."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"250-264","DOI":"10.1038\/s41569-021-00624-2","article-title":"The role of cellular senescence in cardiac disease: basic biology and clinical relevance.","volume":"19","author":"M Mehdizadeh","year":"2022\/04\/01 2022","journal-title":"Nat Rev Cardiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"64520-64533","DOI":"10.18632\/oncotarget.17327","article-title":"Cellular senescence, senescence-associated secretory phenotype, and chronic kidney disease.","volume":"8","author":"W Wang","year":"2017","journal-title":"Oncotarget."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"387-400","DOI":"10.1007\/s10522-022-09972-z","article-title":"Tackling cellular senescence by targeting miRNAs.","volume":"23","author":"Z Wang","year":"2022","journal-title":"Biogerontology."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133668","article-title":"The senescence-associated secretome as an indicator of age and medical risk.","volume":"5","author":"M Schafer","year":"2020","journal-title":"JCI Insight."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"61-74","DOI":"10.1089\/rej.2006.9096","article-title":"Evidence that aging and amyloid promote microglial cell senescence.","volume":"10","author":"B Flanary","year":"2007","journal-title":"Rejuvenation Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41583-020-0366-3","article-title":"Author Correction: Cellular senescence and Alzheimer disease: the egg and the chicken scenario.","volume":"21","author":"S Saez-Atienzar","year":"2020","journal-title":"Nat Rev Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3-11","DOI":"10.1111\/j.1460-9568.2011.07738.x","article-title":"Astrocytes in the aging brain express characteristics of senescence-associated secretory phenotype.","volume":"34","author":"A Salminen","year":"2011","journal-title":"Eur J Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e2219678","DOI":"10.1001\/jamanetworkopen.2022.19678","article-title":"Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome.","volume":"5","author":"B Diniz","year":"2022","journal-title":"JAMA Netw Open."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1362-1383","DOI":"10.1111\/febs.16350","article-title":"Targeting cellular senescence with senotherapeutics: senolytics and senomorphics.","volume":"290","author":"L Zhang","year":"2023","journal-title":"FEBS J."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"75-95","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: from mechanisms to therapeutic opportunities.","volume":"22","author":"R Di Micco","year":"2021","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1038\/s41467-021-25453-2","article-title":"Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice.","volume":"12","author":"E Novais","year":"2021","journal-title":"Nat Commun."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14471","article-title":"A study of the molecular mechanism of quercetin and dasatinib combination as senolytic in alleviating age-related and kidney diseases.","volume":"46","author":"K Alharbi","year":"2022","journal-title":"J Food Biochem."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"446-456","DOI":"10.1016\/j.ebiom.2019.08.069","article-title":"Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.","volume":"47","author":"L Hickson","year":"2019","journal-title":"EBioMedicine."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"554-563","DOI":"10.1016\/j.ebiom.2018.12.052","article-title":"Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study.","volume":"40","author":"J Justice","year":"2019","journal-title":"EBioMedicine."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"22-29","DOI":"10.14283\/jpad.2021.62","article-title":"Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial.","volume":"9","author":"M Gonzales","year":"2022","journal-title":"J Prev Alzheimers Dis."},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104481","article-title":"Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability.","volume":"90","author":"A Nambiar","year":"2023","journal-title":"EBioMedicine."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1-16","DOI":"10.1016\/j.jagp.2023.09.014","article-title":"Geroscience-Centric Perspective for Geriatric Psychiatry: Integrating Aging Biology With Geriatric Mental Health Research.","volume":"32","author":"B Diniz","year":"2023","journal-title":"Am J Geriatr Psychiatry."},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101805","article-title":"Major depression and the biological hallmarks of aging.","volume":"83","author":"E Lorenzo","year":"2023","journal-title":"Ageing Res Rev."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41398-019-0541-3","article-title":"Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults.","volume":"9","author":"B Diniz","year":"2019","journal-title":"Transl. Psychiatry."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"64-72","DOI":"10.1016\/j.jagp.2016.08.018","article-title":"Enhanced Molecular Aging in Late-Life Depression: the Senescent-Associated Secretory Phenotype.","volume":"25","author":"B Diniz","year":"2017","journal-title":"Am J Geriatr Psychiatry."},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12129","article-title":"Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults.","volume":"7","author":"B Diniz","year":"2021","journal-title":"Alzheimers Dement (N Y)."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1376086","DOI":"10.3389\/fragi.2024.1376086","article-title":"Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.","volume":"5","author":"E Lorenzo","year":"2024","journal-title":"Front Aging."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1-7","DOI":"10.1016\/j.jpsychires.2016.07.006","article-title":"Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology.","volume":"82","author":"B Diniz","year":"2016","journal-title":"J Psychiatr Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e9166","DOI":"10.1371\/journal.pone.0009166","article-title":"Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.","volume":"5","author":"E Domenici","year":"2010","journal-title":"PLoS One."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"514-525","DOI":"10.1192\/bjp.2018.144","article-title":"Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses.","volume":"213","author":"T Rowland","year":"2018","journal-title":"Br J Psychiatry."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"29-33","DOI":"10.1016\/j.jpsychires.2018.02.023","article-title":"Oxidative stress markers imbalance in late-life depression.","volume":"102","author":"B Diniz","year":"2018","journal-title":"J Psychiatr Res."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"106-110","DOI":"10.1016\/j.jad.2020.09.084","article-title":"Oxidative DNA damage is increased in older adults with a major depressive episode: A preliminary study.","volume":"279","author":"E Vieira","year":"Jan 15 2021","journal-title":"J Affect Disord."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"518-536","DOI":"10.1111\/joim.13141","article-title":"Senolytic drugs: from discovery to translation.","volume":"288","author":"J Kirkland","year":"2020","journal-title":"J Intern Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"817-837","DOI":"10.1038\/s41573-024-01033-z","article-title":"Therapeutic targeting of senescent cells in the CNS.","volume":"23","author":"M Riessland","year":"2024","journal-title":"Nat Rev Drug Discov."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1973-1974","DOI":"10.1001\/jama.2015.4260","article-title":"Prevalence of the metabolic syndrome in the United States, 2003-2012.","volume":"313","author":"M Aguilar","year":"2015","journal-title":"JAMA."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"306-318","DOI":"10.1093\/schbul\/sbr148","article-title":"Prevalence of Metabolic Syndrome and Metabolic Abnormalities in Schizophrenia and Related Disorders\u2014A Systematic Review and Meta-Analysis.","volume":"39","author":"A Mitchell","year":"2011","journal-title":"Schizophrenia Bull."},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2021.106633","article-title":"Modified Application of Cardiac Rehabilitation in Older Adults (MACRO) Trial: Protocol changes in a pragmatic multi-site randomized controlled trial in response to the COVID-19 pandemic.","volume":"112","author":"D Forman","year":"2022","journal-title":"Contemp Clin Trials."},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1201\/b17442-10","author":"M Konrad","year":"2015","journal-title":"Antioxidants in Sport Nutrition."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"73-82","DOI":"10.1123\/ijsnem.23.1.73","article-title":"Effects of quercetin supplementation on endurance performance and maximal oxygen consumption: a meta-analysis.","volume":"23","author":"D Pelletier","year":"2013","journal-title":"Int J Sport Nutr Exerc Metab."},{"key":"ref47","first-page":"1","article-title":"Dasatinib and Quercetin: Short-Term Simultaneous Administration Improves Physical Capacity In Human.","author":"J Tkemaladze","year":"2019","journal-title":"Apkhazava D"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1111-1115","DOI":"10.1002\/ajh.24186","article-title":"The impact of dasatinib on pregnancy outcomes.","volume":"90","author":"J Cortes","year":"2015","journal-title":"Am J Hematol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21926\/obm.geriatr.1901034","article-title":"Cell Senescence, Telomerase, and Senolytic Therapy.","volume":"3","author":"M Fossel","year":"2019","journal-title":"OBM Geriatrics."},{"key":"ref50","doi-asserted-by":"publisher","article-title":"Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib plus Quercetin to mitigate age-related health and cognitive decline in mental disorders.","DOI":"10.17605\/OSF.IO\/92GMQ"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:05:11Z","timestamp":1748412311000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":50,"URL":"https:\/\/doi.org\/10.12688\/f1000research.151963.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.151963.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.176084.r369668","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.176084.r382393","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.176084.r382393","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.176084.r369668","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.176084.r369668, Amer Burhan, Ontario Shores Centre for Mental Health Sciences, University of Toronto, Toronto, Ontario, 22 Mar 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2#referee-response-369668","order":0,"name":"referee-response-369668","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.166660.r335596, Pierfelice Cutrufelli, University of Catania, Catania, 29 Oct 2024, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/13-1072\/v1#referee-response-335596","order":1,"name":"referee-response-335596","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.176084.r382393, Wan-Ping Lee, University of Pennsylvania, Philadelphia, PA, 28 May 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1072\/v2#referee-response-382393","order":2,"name":"referee-response-382393","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The Foundation for Barnes-Jewish Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}