Investigating sleep efficiency mechanism and its impact on diseases

研究睡眠效率机制及其对疾病的影响

• 批准号: 10663721
• 负责人: YING-HUI FU
• 金额: $ 60.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-25 至 2031-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663721
• 关键词: Aging; Alzheimer' s Disease; Brain; Brain Mapping; Brain region; Development; Disease; Genes; Genetic; Health; Hour; Human; Individual; Knowledge; Life; Longevity; Molecular; Mutation; Nervous System; Neurodegenerative Disorders; Pathology; Pathway interactions; Persons; Population; Probability; Psyche structure; Regulation; Research; Sleep; Sleep Deprivation; Societies; Solid; System; Time; brain cell; cognitive function; mouse model; nervous system disorder; prevent; programs; protective effect; sleep quality; sleep quantity; sleep regulation; trait

Summary Our program aims to seek fundamental knowledge about the brain and nervous system regulating our sleep quality/efficiency and to use that knowledge to reduce the burden of neurological diseases (and probably many others) for all people. Quality sleep is a fundamental necessity for maintaining health and critical for optimal cognitive functioning. Although we have known this for a long time, we have little understanding of how the quality and quantity of sleep are regulated. We began to study individuals with the familial natural short sleep trait more than a decade ago and have now identified a growing list of genes/mutations carried by these individuals. While they are genetically wired to sleep fewer hours per day, they do not desire more sleep and do not seem to suffer the consequences of sleep deficiency and usually live a long and healthy life (both physically and mentally), indicating that they sleep more efficiently. Identifying genetic differences in this population provides solid evidence for the involvement of specific molecules and pathways in regulating sleep quality/efficiency pathways. These molecules offer opportunities to not only reveal the molecular mechanisms but also map brain regions and cells responsible for sleep regulation, thus gaining an understanding of the systems involved in sleep quality/efficiency regulation. We have used our short sleep mouse models and Alzheimer-like disease mouse models to demonstrate that these short sleep mutations offer protective effects against the development and the progression of AD-like pathology. This finding has the revolutionary implication that quality sleep can help prevent many diseases, including neurodegenerative disorders. My research aims to understand how sleep quality is regulated and thus know how quality sleep can be obtained. The results from this research program will have long-lasting beneficial effects on human healthy longevity.

概括 我们的计划旨在寻求有关调节睡眠的大脑和神经系统的基础知识 质量/效率，并利用这些知识来减轻神经系统疾病（可能还有许多疾病）的负担 其他）为所有人。优质睡眠是维持健康的基本必需品，对于保持最佳状态至关重要 认知功能。尽管我们很早就知道这一点，但我们对如何实现这一点却知之甚少。 睡眠质量和数量受到调节。我们开始研究具有家族性自然短睡眠的个体 十多年前的特征，现在已经确定了这些特征所携带的越来越多的基因/突变 个人。虽然他们天生每天睡眠时间较少，但他们并不渴望更多睡眠，而且确实 似乎没有遭受睡眠不足的后果，并且通常过着长寿而健康的生活（无论是身体上还是身体上） 和精神上），表明他们的睡眠效率更高。识别该人群的遗传差异 为特定分子和途径参与调节睡眠提供了坚实的证据 质量/效率途径。这些分子不仅提供了揭示分子机制的机会 还绘制了负责睡眠调节的大脑区域和细胞的图谱，从而了解了 涉及睡眠质量/效率调节的系统。我们使用了我们的短睡眠小鼠模型 阿尔茨海默病小鼠模型证明这些短睡眠突变具有保护作用 对抗 AD 样病理的发生和进展。这一发现具有革命性意义 优质睡眠有助于预防许多疾病，包括神经退行性疾病。我的研究目的是 了解睡眠质量是如何调节的，从而知道如何获得高质量的睡眠。结果来自 这项研究计划将对人类的健康长寿产生持久的有益影响。