A pilot study of senolytics to improve cognition and mobility in older adults at risk for Alzheimer’s disease

作者：Courtney Millar, Ike Iloputaife, Kathryn Baldyga, Amani M. Norling, Afroditi Boulougoura, Theodoros Vichos, Tamar Tchkonia, Aaron Deisinger, Tamar Pirtskhalava, James L. Kirkland, Thomas G. Travison, Lewis A. Lipsitz · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105612 · 被引用次数：76 · 研究领域：Telomeres, Telomerase, and Senescence、Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments

BACKGROUND: This single-arm study evaluates the feasibility, safety, and preliminary effects of two senolytic agents, Dasatinib and Quercetin (DQ), in older adults at risk of Alzheimer's disease. METHODS: Participants took 100 mg of Dasatinib and 1250 mg of Quercetin for two days every two weeks over 12 weeks. Recruitment rate, adverse events, absolute changes in functional outcomes, and percent changes in biomarkers were calculated. Spearman correlations between functional and biomarker outcomes were performed. FINDINGS: Approximately 10% of telephone-screened individuals completed the intervention (n = 12). There were no serious adverse events related to the intervention. Mean Montreal Cognitive Assessment (MoCA) scores non-significantly increased following DQ by 1.0 point (95% CI: -0.7, 2.7), but increased significantly by 2.0 points (95% CI: 0.1, 4.0) in those with lowest baseline MoCA scores. Mean percent change in tumour necrosis factor-alpha (TNF-α), a key product of the senescence-associated secretory phenotype (SASP), non-significantly decreased following DQ by -3.0% (95% CI: -13.0, 7.1). Changes in TNF-α were significantly and inversely correlated with changes in MoCA scores (r = -0.65, p = 0.02), such that reductions in TNF- α were correlated with increases in MoCA scores. INTERPRETATION: This study suggests that intermittent DQ treatment is feasible and safe; data hint at potential functional benefits in older adults at risk of Alzheimer's disease. The observed re...