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

项目摘要/摘要 候选人：Stefano Tarantini，博士，该大学老年科学中心的年轻助理教授 俄克拉何马州的HSC。塔兰蒂尼博士的研究重点是与年龄相关的脑血液调节失调的作用 Flow在血管性认知障碍和痴呆(VCID)发病机制中的作用塔兰蒂尼博士的长期目标是 独立领导一个由联邦政府资助的实验室，专注于研究 VCID的发病机制，并针对衰老的基本机制开发新的预防干预措施。 职业发展：这个R03奖项将支持塔兰蒂尼博士对一项新的先导性研究的研究努力 基于他过去在脑血管病理生理学方面的经验，先进的双光子成像， 转录学、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：俄克拉荷马大学老年科学中心是 VCID研究，是塔兰蒂尼博士职业发展的理想环境，提供所有资源 这是成功完成拟议研究所必需的。这项建议建立在现有的显著优势基础上： 多学科专业知识、尖端核心设施基础设施、高度协作的环境以及 非常成功的初级教师指导模式。 研究：该提案旨在调查限时喂食(TRF)对儿童的潜在作用 与年龄相关的血管认知障碍的发展。营养干预，如热量限制(CR) 已被证明对血管内皮细胞功能障碍有积极作用，但对CR和 对老年人的一些有害影响促使研究替代的可翻译策略的必要性 抗老年人认知功能减退。在已有初步数据的基础上，提出了中心假设 TRF逆转了年龄诱导的内皮功能障碍，并改善了CBF和NVC反应。据预测， 由此产生的神经血管恢复有助于认知功能的恢复。以下是目标 建议：1)确定TRF方案如何影响内皮细胞介导的神经血管偶联反应 老龄化；2)确定TRF作为一种生活方式干预如何改变衰老的多个认知域。那些研究表明 将调查导致VCID发病的途径，并提供 预防老年人认知功能丧失的潜在治疗策略。 交付成果：拟议研究的结果将提供对内皮细胞的机械性洞察 对与年龄相关的VCID的贡献，并为发展营养生活方式提供概念验证 预防的干预策略。

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.