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

描述(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，并增加发病和死亡的风险。一个悬而未决的问题是：睡眠不佳如何导致健康恶化，特别是在衰老过程中。导致细胞老化的炎症和细胞应激都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，减少端粒酶，并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。这项建议的总体目标是应用生物行为框架来研究老年人睡眠与健康的关系。目标。要做到这一点，我 将：1)获得睡眠、衰老和基因表达方面的培训；2)通过使用动脉粥样硬化多种族研究(MESA)进行分析，测试睡眠不足对健康的生物行为机制，检查睡眠障碍、睡眠数量和睡眠深度对10年来端粒损失率的贡献；3)实验测试在部分睡眠剥夺一晚(研究2)和12周(研究3)时，老年人(60岁)受到干扰的炎症、细胞应激和细胞衰老基因表达途径。意义重大。这项独特的跨学科工作将通过更好地定义睡眠影响晚年疾病脆弱性的生物学机制之一，推动生物医学睡眠研究领域的发展。

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.