Schweiger Abigail, Diniz Breno, Nicol Ginger, Schweiger Julie, Dasklakis-Perez Andes E, Lenze Eric J
Social Work, Saint Louis University School of Social Work, St. Louis, Missouri, 63103, USA.
Psychiatry, Washington University in St Louis School of Medicine, St. Louis, Missouri, 63108, USA.
F1000Res. 2025 Mar 5;13:1072. doi: 10.12688/f1000research.151963.2. eCollection 2024.
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).
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.
This pilot aims to evaluate the safety and feasibility of the senolytic regimen and D+Q's potential to counteract accelerated aging in adults with schizophrenia/schizoaffective disorder and TRD.
Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders is registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.
重度抑郁症（MDD）和精神分裂症与加速衰老有关，导致寿命缩短、健康寿命缩短和认知能力下降。细胞衰老过程中，细胞失去增殖能力并形成衰老相关分泌表型（SASP），在此过程中发挥作用。新出现的研究表明，达沙替尼+槲皮素（D+Q）的衰老细胞溶解疗法可减少衰老细胞，可能减轻与年龄相关的健康和认知能力下降。这项初步研究旨在评估D+Q在患有精神分裂症、分裂情感性障碍和难治性抑郁症（TRD）的老年人中的可行性和安全性。
这项单中心研究将总共招募30名年龄在50岁及以上的精神分裂症/分裂情感性障碍患者或60岁及以上的TRD患者；年龄限制的差异是因为由于代谢负担，精神分裂症患者的生理年龄比一般人群大约大10岁。每位参与者在基线以及第1至3周将连续两天口服100毫克达沙替尼加1250毫克槲皮素（即服药两天，停药五天），同时接受生活方式风险管理教育。问卷和评估将在基线、第10周和1年时测量健康和认知功能以及精神功能。磁共振成像（MRI）将在基线和10周时测量大脑的结构和功能健康。在七个时间点进行血液采样以检测SASP：基线、第1至4周、第10周和1年。
这项初步研究旨在评估衰老细胞溶解疗法的安全性和可行性，以及D+Q抵消精神分裂症/分裂情感性障碍和TRD成人加速衰老的潜力。
“达沙替尼加槲皮素治疗精神障碍加速衰老”已在ClinicalTrials.gov上注册：NCT05838560；于2023年5月1日发布。
