Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementia

限时喂养（TRF）用于预防与年龄相关的血管性认知障碍和痴呆

• 批准号: 10303643
• 负责人: Stefano Tarantini
• 金额: $ 29万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303643
• 关键词: Adherence; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Attenuated; Award; Bioinformatics; Biology; Blood Vessels; Brain; Caloric Restriction; Calories; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cognitive; Consumption; Core Facility; Coupling; Data; Developed Countries; Development; Diet Habits; Dietary Intervention; Doctor of Philosophy; Elderly; Endothelium; Energy Intake; Environment; Fasting; Functional disorder; Funding; Genetic; Geroscience; Goals; Health; Homeostasis; Hour; Human; Hyperemia; Image; Impaired cognition; Impairment; Individual; Infrastructure; Intake; Intermittent fasting; Laboratories; Laser Speckle Imaging; Lead; Longevity; Mediating; Metabolic; Modeling; Mus; Neurons; Nutritional; Oklahoma; Oxidation-Reduction; Oxidative Stress; Oxygen; Pathogenesis; Pathway interactions; Persons; Pharmacology; Pilot Projects; Play; Prevention; Public Health; Publishing; Regimen; Rejuvenation; Research; Research Proposals; Resources; Role; SIRT1 gene; Stimulus; Testing; Therapeutic; Therapeutic Intervention; Time; Time-restricted feeding; Universities; Vascular Cognitive Impairment; Vascular blood supply; Vasodilation; Work; age related; aged; aging brain; anti aging; base; career development; cerebrovascular; cognitive benefits; cognitive function; cognitive testing; collaborative environment; cost estimate; endothelial dysfunction; experience; faculty mentor; feeding; gain of function; human old age (65+); improved; insight; lifestyle factors; lifestyle intervention; multidisciplinary; neurovascular; neurovascular coupling; novel; nutrition; pre-clinical; prevent; preventive intervention; professor; programs; protective effect; response; restoration; tool; transcriptomics; translatable strategy; translational barrier; two-photon; vascular cognitive impairment and dementia; Adherence; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Attenuated; Award; Bioinformatics; Biology; Blood Vessels; Brain; Caloric Restriction; Calories; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cognitive; Consumption; Core Facility; Coupling; Data; Developed Countries; Development; Diet Habits; Dietary Intervention; Doctor of Philosophy; Elderly; Endothelium; Energy Intake; Environment; Fasting; Functional disorder; Funding; Genetic; Geroscience; Goals; Health; Homeostasis; Hour; Human; Hyperemia; Image; Impaired cognition; Impairment; Individual; Infrastructure; Intake; Intermittent fasting; Laboratories; Laser Speckle Imaging; Lead; Longevity; Mediating; Metabolic; Modeling; Mus; Neurons; Nutritional; Oklahoma; Oxidation-Reduction; Oxidative Stress; Oxygen; Pathogenesis; Pathway interactions; Persons; Pharmacology; Pilot Projects; Play; Prevention; Public Health; Publishing; Regimen; Rejuvenation; Research; Research Proposals; Resources; Role; SIRT1 gene; Stimulus; Testing; Therapeutic; Therapeutic Intervention; Time; Time-restricted feeding; Universities; Vascular Cognitive Impairment; Vascular blood supply; Vasodilation; Work; age related; aged; aging brain; anti aging; base; career development; cerebrovascular; cognitive benefits; cognitive function; cognitive testing; collaborative environment; cost estimate; endothelial dysfunction; experience; faculty mentor; feeding; gain of function; human old age (65+); improved; insight; lifestyle factors; lifestyle intervention; multidisciplinary; neurovascular; neurovascular coupling; novel; nutrition; pre-clinical; prevent; preventive intervention; professor; programs; protective effect; response; restoration; tool; transcriptomics; translatable strategy; translational barrier; two-photon; vascular cognitive impairment and dementia

PROJECT SUMMARY/ABSTRACT Candidate: Stefano Tarantini, PhD is a young assistant professor in the Center for Geroscience at the University of Oklahoma HSC. Dr. Tarantini’s research is focused on the role of age-related dysregulation of cerebral blood flow in the pathogenesis of Vascular Cognitive Impairment and Dementia (VCID). Dr. Tarantini’s long-term goal is to independently lead a federally funded laboratory with research focused on the underlying causes for the pathogenesis of VCID, and development of novel interventions for prevention targeting basic mechanisms of aging. Career Development: This R03 award will support Dr. Tarantini’s research efforts investigating a novel pilot study building on his past experience in cerebrovascular pathophysiology, advanced two-photon imaging, transcriptomics, bioinformatics, cognitive testing, redox biology and metabolic biology. Rich research environment: The Center for Geroscience at University of Oklahoma HSC is a leading center in VCID research and is an ideal environment for Dr. Tarantini’s career development, providing all the resources required to successfully complete the proposed studies. This proposal builds on the existing significant strengths: multidisciplinary expertise, cutting-edge core facility infrastructure, highly collaborative environment, and an exceptionally successful model for junior faculty mentoring. Research: The proposal aims to investigate the potential role of time-restricted feeding (TRF) against the development of age-related vascular cognitive impairment. Nutritional interventions such as caloric restriction (CR) have been shown to exert positive effects against endothelial dysfunction however poor adherence to CR and some deleterious effects in older individuals generate the need to investigate alternative translatable strategies against cognitive decline in the elderly. On the basis of extant preliminary data, the central hypothesis is proposed that TRF reverses age-induced endothelial dysfunction and improves CBF and NVC responses. It is predicted that the resulting neurovascular rejuvenation contributes to restoration of cognitive function. The following aims are proposed: 1) Determine how TRF regimen affects endothelium-mediated neurovascular coupling responses in aging; 2) Determine how TRF as a lifestyle intervention alters multiple cognitive domains in aging. The studies that have been highlighted in this proposal will investigate pathways that lead to the pathogenesis of VCID and offer potential therapeutic strategies to prevent the loss of cognitive function in the elderly. Deliverables: The results from the proposed studies will provide mechanistic insight into the endothelial contributions to age-related VCID and provide proof-of-concept for the development of nutritional lifestyle intervention strategies for prevention.

项目摘要/摘要 候选人：Stefano Tarantini，博士是该大学Geroscience中心的年轻助理教授 俄克拉荷马州HSC。塔兰蒂尼（Tarantini）博士的研究重点是与年龄相关的脑血液失调的作用 血管认知障碍和痴呆（VCID）发病机理中的流动。塔兰蒂尼博士的长期目标是 独立领导联邦资助的实验室，研究着重于研究的根本原因 VCID的发病机理，以及针对衰老基本机制的预防新干预措施的发展。 职业发展：该R03奖将支持Tarantini博士的研究工作调查一项新型试点研究 基于他过去在脑血管病理生理学的经验，高级两光子成像， 转录组学，生物信息学，认知测试，氧化还原生物学和代谢生物学。 丰富的研究环境：俄克拉荷马大学HSC大学的Geroscience中心是领先的中心 VCID研究是Tarantini博士职业发展的理想环境，提供了所有资源 需要成功完成所提出的研究。该提案以现有的重要优势为基础： 多学科专业知识，尖端的核心设施基础设施，高度协作环境和 初级教师指导的模型非常成功。 研究：该提案旨在调查时间限制喂养（TRF）的潜在作用 与年龄有关的血管认知障碍的发展。营养干预措施，例如热量限制（CR） 已证明对内皮功能障碍产生积极影响，但是对CR的依从性较差 老年人中的一些有害影响产生了调查替代可翻译策略的需求 反对古老的认知能力下降。根据额外的初步数据，提出了中心假设 TRF逆转了年龄引起的内皮功能障碍并改善了CBF和NVC响应。可以预测 由此产生的神经血管修订有助于恢复认知功能。以下目标是 提议：1）确定TRF方案如何影响内皮介导的神经血管耦合反应 老化; 2）确定TRF作为生活方式干预如何改变衰老中的多个认知领域。研究 该提案中已突出显示的将研究导致VCID发病机理的途径并提供 潜在的治疗策略，以防止老年认知功能的丧失。 可交付成果：拟议研究的结果将提供对内皮的机械洞察力 对与年龄有关的VCID的贡献，并为营养生活方式的发展提供了概念验证 预防干预策略。