Late life sleep disturbances: Effects on cell stress, telomerase, inflammation

描述（由申请人提供）：晚年睡眠不足被认为会导致身体和精神功能下降，并增加发病率和死亡率的风险。一个尚未解决的问题是：睡眠不足是如何导致健康状况恶化的，尤其是在衰老方面。炎症和细胞应激都有助于细胞衰老，被认为是睡眠不足影响疾病的生物学途径。我认为老年人睡眠不足会改变细胞内环境，降低端粒酶，增加与细胞应激反应、炎症活动和衰老信号表达一致的基因表达模式。这项提议的首要目标是应用生物行为框架来研究老年人的睡眠健康关系。目标。为了做到这一点

DESCRIPTION (provided by applicant): Insufficient sleep in later life is thought to contribute to declines in physical and mental functioning, and increase risk for morbidity and mortality. A yet unanswered question is: how does poor sleep contributes to worse health, particularly in aging. Both inflammation and cellular stress, which contribute to aging of cells, are proposed biological pathways through which sleep loss influences disease. I propose that sleep deprivation in older adults will alter the intracellular environment, decrease telomerase, and increase gene expression patterns consistent with cellular stress responses, inflammatory activity, and senescent signal expression. The over-arching objective of this proposal is to apply a biobehavioral framework to study the sleep-health relationship in older adults. Aims. To do this I will: 1) obtain training in sleep, aging, and gene expression, 2) test biobehavioral mechanisms of sleep loss on health by conducting analyses using the Multi-Ethnic Study of Atherosclerosis (MESA), examining the contribution of sleep disturbances, sleep quantity, and sleep depth to rates of telomere attrition over 10 years, and 3) experimentally test the inflammatory, cellular stress, and cell senescence gene expression pathways that are disrupted from one night (Study 2) and 12 weeks (Study 3) of partial sleep deprivation in older adults (ages 60+). Significance. This unique interdisciplinary work will advance the field of biomedical sleep research by better defining one of the biological mechanisms through which sleep influences disease vulnerability in late life.