Investigating sleep efficiency mechanism and its impact on diseases

摘要 我们的计划旨在寻求有关大脑和调节我们睡眠的神经系统的基本知识 质量/效率，并利用这一知识来减轻神经系统疾病的负担(可能还有许多 其他人)为所有人。高质量的睡眠是保持健康的基本必要条件，对最佳睡眠至关重要 认知功能。虽然我们知道这一点很久了，但我们对 睡眠的质量和数量是有规律的。我们开始研究家族性自然短睡眠的个体。 特征，现在已经发现了越来越多的由这些基因/突变携带的基因/突变 个人。虽然他们天生每天的睡眠时间较少，但他们并不想要更多的睡眠，而是 似乎没有遭受睡眠不足的后果，通常过着健康长寿的生活(在身体上 和精神上)，这表明他们睡得更有效率。确定这一群体的遗传差异 为特定分子和途径参与调节睡眠提供了确凿的证据 质量/效率路径。这些分子不仅提供了揭示分子机制的机会 而且还绘制出负责睡眠调节的大脑区域和细胞图，从而了解 参与睡眠质量/效率调节的系统。我们使用了我们的短睡眠小鼠模型和 阿尔茨海默病样疾病小鼠模型证明这些短睡眠突变提供保护作用 抗阿尔茨海默病的发生和发展。这一发现具有革命性的意义 高质量的睡眠有助于预防许多疾病，包括神经退行性疾病。我的研究旨在 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。结果来自于 这项研究计划将对人类的健康长寿产生长期的有益影响。

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.