Time restricted eating for prevention of age-related vascular cognitive decline in older adults

限制饮食时间以预防老年人与年龄相关的血管认知能力下降

基本信息

批准号：
10739956
负责人：
Stefano Tarantini
金额：
$ 21.75万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739956
关键词：
Address Adherence Affect Age Age Years Age-associated memory impairment Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Animal Model Attenuated Biological Availability Blood Blood Vessels Brain Brain region Caloric Restriction Calories Cerebrovascular Circulation Cerebrum Clinical Clinical Research Clinical Trials Cognition Cognitive Communities Consumption Data Deacetylation Dementia Development Diet Habits Dietary Intervention Eating Elderly Endothelial Cells Endothelium Energy Intake Fasting Functional disorder Goals Health Hour Human Hyperemia Impaired cognition Impairment Individual Inflammation Intake Intermittent fasting Laser Speckle Imaging Link Literature Longevity Mediating Mus Neurons Nutrient Oxidative Stress Oxygen Participant Pathogenesis Pathway interactions Performance Peripheral Play Prevention Prevention approach Public Health Publishing Research Role SIRT1 gene Series Serum Stimulus Testing Therapeutic Intervention Time Time-restricted feeding Vascular Cognitive Impairment Vascular Endothelium Vascular blood supply Vasodilation age related aged anti aging brain endothelial cell cerebrovascular cerebrovascular health circulating biomarkers clinically relevant cognitive function cognitive performance cognitive testing design functional near infrared spectroscopy high risk human subject improved improved outcome innovative technologies lifestyle factors lifestyle intervention neurovascular neurovascular coupling novel therapeutic intervention nutrition pre-clinical preservation prevent response retina blood vessel structure translational barrier

Address Adherence Affect Age Age Years Age-associated memory impairment Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Animal Model Attenuated Biological Availability Blood Blood Vessels Brain Brain region Caloric Restriction Calories Cerebrovascular Circulation Cerebrum Clinical Clinical Research Clinical Trials Cognition Cognitive Communities Consumption Data Deacetylation Dementia Development Diet Habits Dietary Intervention Eating Elderly Endothelial Cells Endothelium Energy Intake Fasting Functional disorder Goals Health Hour Human Hyperemia Impaired cognition Impairment Individual Inflammation Intake Intermittent fasting Laser Speckle Imaging Link Literature Longevity Mediating Mus Neurons Nutrient Oxidative Stress Oxygen Participant Pathogenesis Pathway interactions Performance Peripheral Play Prevention Prevention approach Public Health Publishing Research Role SIRT1 gene Series Serum Stimulus Testing Therapeutic Intervention Time Time-restricted feeding Vascular Cognitive Impairment Vascular Endothelium Vascular blood supply Vasodilation age related aged anti aging brain endothelial cell cerebrovascular cerebrovascular health circulating biomarkers clinically relevant cognitive function cognitive performance cognitive testing design functional near infrared spectroscopy high risk human subject improved improved outcome innovative technologies lifestyle factors lifestyle intervention neurovascular neurovascular coupling novel therapeutic intervention nutrition pre-clinical preservation prevent response retina blood vessel structure translational barrier

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项目摘要

PROJECT SUMMARY/ABSTRACT Cognitive impairment associated with Alzheimer’s disease and Related Dementias (ADRD) and aging has emerged as one of the major public health challenges of our time. Recent clinical studies, as well as those in animal models, support that preservation of cognitive health depends on an adequate cerebral blood flow (CBF) supply to the active brain regions. Importantly, in the healthy, young brain cerebral blood supply is readily adjusted to meet the increased oxygen and nutrient demand of activated neurons. This homeostatic mechanism, termed "neurovascular coupling" (NVC) or "functional hyperemia", is required for normal brain function. Preclinical and clinical evidence shows that aging per se significantly impairs endothelium mediated NVC responses, which play a causal role in age- related vascular cognitive impairment (VCI) and the development of ADRD. Lifestyle factors, including nutrition and dietary habits, significantly affect cerebrovascular health and, thereby, influence the pathogenesis of age-related cognitive impairment and ADRD. Caloric restriction (CR), which exerts multifaceted anti-aging and lifespan-extending effects, has been demonstrated to be an effective nutritional intervention that can improve vascular health and cognitive function. CR activates SIRT1-dependent pathways in the vasculature, which attenuates cellular oxidative stress and rescues endothelial vasodilation. However, adherence to CR remains a challenge and a translational barrier as most humans may not be able, or willing, to reduce their caloric intake by 30% over extended periods of time. Intermittent fasting can recapitulate the benefits of CR without limiting calorie intake in older adults. Time restricted eating (TRE) is considered the best approach to intermittent fasting for elderly individuals as it allows consumption of required calories within a condensed daily eating window (4-10 hours), resulting in the greatest fasting stimulus without a net reduction in calorie intake. Yet, the impact of TRE on cerebrovascular function and, potentially the delay of ADRD and age-related VCI, to preserve cognition is currently unknown. Our central hypothesis is that closer adherence to TRE will improve NVC responses and micro- and macrovascular endothelial function, potentially through activation of SIRT1-dependent vasoprotective pathways, resulting in the improvement of cognitive performance. This hypothesis will be tested by assessing the effects of TRE (10 hours eating window) in community dwelling older adults (55-80 years of age) in a 6-month study. Aim 1 will determine the impact of TRE on NVC responses using innovative technologies such as functional near-infrared spectroscopy (fNIRS) and dynamic retinal vessel analysis (DVA), and on microvascular endothelial function using laser speckle contrast imaging and flow-mediated dilation approaches in community dwelling older adults. Aim 2 will determine the impact of TRE on circulating biomarkers and cerebromicrovascular endothelial cell SIRT1 activity.

项目摘要/摘要与阿尔茨海默氏病和相关痴呆症（ADRD）和衰老有关的认知障碍成为我们这个时代的主要公共卫生挑战之一。最近的临床研究以及动物的研究模型，支持认知健康的支持取决于足够的脑血流（CBF）供应活跃的大脑区域。重要的是，在健康的，年轻的大脑大脑脑供应中，很容易调整以满足激活神经元的氧气和营养需求增加。这种稳态机制，称为“神经血管正常脑功能需要耦合“（NVC）或“功能性充血”。临床前和临床证据表明，衰老本身显着损害内皮介导的NVC反应，这在年龄中起因果作用相关的血管认知障碍（VCI）和ADRD的发展。生活方式因素，包括营养和饮食习惯，都显着影响脑血管健康，从而影响与年龄相关的认知障碍和ADRD的发病机理。锻炼的热量限制（CR）多方面的抗衰老和寿命扩展效果已被证明是有效的营养可以改善血管健康和认知功能的干预措施。 CR激活SIRT1依赖性途径脉管系统减弱了细胞氧化物胁迫并营救内皮血管舒张。但是，坚持 CR仍然是一个挑战和转化障碍，因为大多数人可能无法或愿意减少热量在长时间内摄入30％。间歇性禁食可以概括CR的好处而无需限制老年人的卡路里摄入量。时间限制饮食（TRE）被认为是间歇性禁食的最佳方法老年人允许在每日凝结的饮食窗口（4-10小时）中消耗所需卡路里，导致最大的禁食刺激，而不会减少卡路里摄入量。然而，tre的影响目前未知。我们的核心假设是，对TRE的紧密依从性将改善NVC响应以及微观和微观和微观。大血管内皮功能，可能通过激活SIRT1依赖性血管保护途径，导致认知表现的改善。该假设将通过评估一项为期6个月的研究，在社区居住的老年人（55-80岁）中的TRE（10小时进食窗口）。目标1意志使用创新技术（例如功能近红外）确定TRE对NVC响应的影响光谱（FNIRS）和动态视网膜血管分析（DVA），以及使用微血管内皮功能激光斑点对比度成像和流动介导的词典方法在社区居住的老年人中。 AIM 2意志确定TRE对循环生物标志物和脑血管内皮细胞SIRT1活性的影响。