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

晚年睡眠障碍：对细胞应激、端粒酶、炎症的影响

• 批准号: 8635896
• 负责人: Judith E Carroll
• 金额: $ 12.58万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635896
• 关键词: Adult; Affect; Age; Aging; Atherosclerosis; Awareness; Biological; Biological Markers; Biology; Cardiovascular Diseases; Cell Aging; Cell division; Cells; Cellular Stress; Cellular Stress Response; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chromosomes; Control Groups; DNA; Data; Disease; Elderly; Environment; Epidemiology; Event; Excision; Exhibits; Failure; Frequencies; Gene Expression; Gene Expression Profile; Genomics; Goals; Health; Healthy People 2020; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Laboratories; Length; Leukocytes; Life; Link; Longevity; Malignant Neoplasms; Measurement; Measures; Metabolic; Mitochondria; Mitotic; Modeling; Molecular Profiling; Morbidity - disease rate; Mus; Oxidative Stress; Pathology; Pathway interactions; Pattern; Physiological; Physiology; Positioning Attribute; Premature aging syndrome; Psyche structure; Public Health; Quality of life; Randomized; Reporting; Research; Research Design; Research Proposals; Risk; Sampling; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; Sleeplessness; System; Techniques; Telomerase; Telomere Maintenance; Telomere Shortening; Testing; Tissues; Training; Up-Regulation; Work; age related; aging gene; base; biobehavior; biological adaptation to stress; career; cell age; design; disorder risk; experience; human old age (65+); improved; indexing; innovation; meetings; mortality; prospective; protein complex; research study; senescence; telomere

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.

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。一个尚未回答的问题是：睡眠不足如何导致健康状况恶化，特别是在衰老方面。炎症和细胞应激都是导致细胞老化的原因，被认为是睡眠不足影响疾病的生物学途径。我认为，老年人睡眠不足将改变细胞内环境，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。这项建议的首要目标是应用生物行为框架来研究老年人的睡眠与健康的关系。目标。为此，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的多种族研究（梅萨）进行分析来测试睡眠丧失对健康的生物行为机制，检查10年内睡眠障碍、睡眠量和睡眠深度对端粒磨损率的贡献，以及3）实验性测试炎症、细胞应激，和细胞衰老基因表达途径，从一个晚上（研究2）和12周（研究3）的部分睡眠剥夺老年人（年龄60岁以上）中断。意义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，推进生物医学睡眠研究领域。