GENETIC ANALYSIS OF SLEEP SENECENCE

衰老与人类、猴子、狗、猫、大鼠、小鼠和苍蝇的睡眠中断有关。在人类和遗传模式生物黑腹果蝇中，睡眠不足始于中年，并随着年龄的增长而变得更加明显。重要的是，睡眠时间和失眠与全因死亡率的增加有关。此外，睡眠不足对代谢过程、内分泌和免疫功能的不利影响可能会增加个人对严重疾病的易感性，包括肥胖、II型糖尿病和冠心病。这些数据表明，睡眠调节途径中与年龄相关的功能下降可能会改变其他系统中功能性衰老的时间进程。不幸的是，在睡眠调节中控制衰老的遗传机制及其对其他器官系统的影响尚不清楚。在拟开展的研究中，我们将：1)评估衰老过程中睡眠质量与神经元可塑性的关系；2)确定胰岛素/TOR信号在控制年龄相关睡眠缺陷和神经元可塑性中的遗传需求；3)筛选睡眠衰老的基因抑制因子。

Aging is associated with sleep disruptions in humans, monkeys, dogs, cats, rats, mice, and flies. In humans, and in the genetic model organism Drosophila melanogaster, sleep deficits begin during middle age and become more pronounced with age. Importantly, sleep duration and insomnia have been linked with an increased risk of all-cause mortality. Moreover, the adverse effects of sleep loss on metabolic processes, endocrine and immunological functions may increase the susceptibility of individuals to serious diseases,including obesity, type II diabetes and coronary heart disease. These data suggest that age-related functional declines in sleep regulatory pathways may alter the time-course of functional senescence in other systems. Unfortunately, the genetic mechanisms that control senescence in sleep regulation and their impact on other organ systems are unknown. In the proposed studies we will: 1) evaluate the relationship between sleep-quality and neuronal plasticity during aging; 2) determine the genetic requirements of insulin/TOR signaling in controlling age-related deficits in sleep and neuronal plasticity; 3) screen for genetic suppressors of sleep aging.