Senolytics to Improve Cognition and Mobility in Older Adults at Risk of Alzheimer’s Disease

Senolytics 可改善有阿尔茨海默病风险的老年人的认知和活动能力

• 批准号: 10551712
• 负责人: LEWIS LIPSITZ
• 金额: $ 7.86万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551712
• 关键词: Activities of Daily Living; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Biological Markers; Blood; Blood flow; Boston; Brain region; Capsicum; Cells; Cerebrovascular Circulation; Clinic; Cocoa Powder; Cognition; Dasatinib; Data; Development; Dose; Elderly; Etiology; Flavanol; Gait speed; Geroscience; Goals; Human; Impairment; Interruption; Lead; Measures; Mus; Neurofibrillary Tangles; Physical Performance; Pilot Projects; Quercetin; Regimen; Regulation; Research; Resources; Rest; Risk; Serum; Testing; Tissues; Tyrosine Kinase Inhibitor; Urine; Ventricular; age related; aged; arm; base; cognitive disability; cognitive performance; cognitive task; density; executive function; functional disability; idiopathic pulmonary fibrosis; improved; mild cognitive impairment; neuron loss; neurovascular coupling; novel strategies; open label; prevent; recruit; response; senescence

Project Summary: Abnormalities in cognition and mobility are common accompaniments of aging that often precede the development of Alzheimer's disease. Among their many etiologies, these abnormalities are associated with alterations in the regulation of cerebral blood flow to frontal regions of the brain that subserve executive functions and gait speed. We have previously shown that treatment with cocoa flavanols can improve blood flow in response to a cognitive task (neurovascular coupling [NVC]), as well as executive function in older people with impaired NVC. These compounds can also reduce the number of senescent cells and their toxic secretory products (SASP) in a variety of tissues. In mice, “senolytic” compounds such as flavanols and tyrosine kinase inhibitors, have been shown to reduce neurofibrillary tangle density, neuron loss, and ventricular enlargement, and in humans with idiopathic pulmonary fibrosis, improve gait speed and other functional abilities. Based on these findings, we hypothesize that the flavanol, Quercetin, and tyrosine kinase inhibitor, Dasatinib, (Q+D) will improve NVC in response to an executive task, reduce circulating SASP components, and in so doing, improve cognition and mobility in older adults who are at risk of Alzheimer's disease.

项目摘要： 认知和流动性异常是衰老的共同安排 在阿尔茨海默氏病的发展之前。在他们的许多病因中，这些 异常与调节脑血流调节的改变有关 大脑的区域，可以使执行功能并获得速度。我们以前有 表明可可黄烷醇的治疗可以响应认知能够改善血液流动 任务（神经血管耦合[NVC]），以及患有受损的老年人的执行功能 NVC。这些化合物还可以减少感觉细胞的数量及其有毒 各种组织中的分泌产物（SASP）。在小鼠中，“鼻溶剂”化合物，例如 黄烷醇和酪氨酸激酶抑制剂已被证明可减少神经纤维缠结 密度，神经元丧失和心室膨胀，以及特发性肺的人类 纤维化，提高对齐速度和其他功能能力。基于这些发现，我们 假设黄酮醇，槲皮素和酪氨酸激酶抑制剂达沙替尼（q+d）将 改善NVC来响应执行任务，减少循环的SASP组件，并因此 这样做，改善有阿尔茨海默氏病风险的老年人的认知和流动性。