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.

项目概要： 认知和行动能力异常是衰老的常见伴随现象， 在其众多病因中，这些先于阿尔茨海默病的发展。 异常与额叶脑血流调节的改变有关 我们之前已经了解了促进执行功能和步态速度的大脑区域。 研究表明，用可可黄烷醇治疗可以改善认知能力的血液流动 任务（神经血管耦合 [NVC]）以及老年人执行功能受损 NVC。这些化合物还可以减少衰老细胞的数量及其毒性。 小鼠多种组织中的分泌产物（SASP），例如“衰老”化合物。 黄烷醇和酪氨酸激酶抑制剂已被证明可以减少神经原纤维缠结 密度、神经元损失和心室扩大，以及患有特发性肺病的人类 根据这些发现，我们可以减少纤维化，提高步态速度和其他功能能力。 随后黄烷醇、槲皮素和酪氨酸激酶抑制剂达沙替尼 (Q+D) 将 改进 NVC 以响应执行任务，减少循环 SASP 组件，从而 这样做，可以改善有阿尔茨海默病风险的老年人的认知能力和活动能力。