The Interplay Between Sleep, Melatonin, and Mortality in Older Men

老年男性睡眠、褪黑激素和死亡率之间的相互作用

• 批准号: 7528795
• 负责人: EVA S SCHERNHAMMER
• 金额: $ 33.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7528795
• 关键词: 25-hydroxyvitamin D; Address; Age; Aging; American; Americas; Ancillary Study; Antioxidants; Archives; Attenuated; Biological Clocks; Centenarian; Cessation of life; Characteristics; Circadian Rhythms; Cognition; Cognitive; Cohort Studies; Condition; Darkness; Data; Disease; Economics; Elderly; Elderly man; Fracture; Frequencies; Future; Gait; Home environment; Hormones; Hour; Human; Hypothalamic structure; Impaired cognition; Individual; Intervention Studies; Life; Light; Link; Longevity; Maintenance; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Melatonin; Morbidity - disease rate; Napping; Outcome Study; Participant; Pathway interactions; Performance; Physical Function; Physiology; Polysomnography; Population; Production; Property; Psyche structure; Public Health; Quality of life; Questionnaires; REM Sleep; Research; Resources; Risk; Role; SF-12; Sampling; Score; Serum; Sleep; Sleep Architecture; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Slow-Wave Sleep; Societies; Speed; Sunlight; System; Testing; Time; United States; Urination; Urine; Variant; Visit; Vitamin D; actigraphy; age related; base; cancer risk; cognitive function; cohort; follow-up; functional status; healthy aging; improved; men; mortality; muscle strength; novel; older men; osteoporosis with pathological fracture; prospective; research study; sleep onset; trait; urinary

DESCRIPTION (provided by applicant): There is mounting evidence for an association between sleep disorders, the circadian system, and longevity. Though the physiology of this has largely remained speculative, studies suggest that melatonin may be a possible link between sleep disorders and mortality. Melatonin, a cancer-protective hormone that is intimately linked to the circadian system in humans, has been implicated in longevity by experimental studies, but no studies in humans have been conducted, to date. In addition, little is known about the factors associated with melatonin, including melatonin's relation with sleep characteristics. Vitamin D, for the creation of which sun light is necessary, appears to reduce mortality and has been shown to lower fracture risk in elderly. How melatonin and vitamin D, both acutely sensitive to light, are linked with each other, has never been studied. We will evaluate relationships between sleep characteristics, melatonin, and longevity in a prospective cohort of elderly men. We will utilize a subcohort of the MrOS main cohort, the MrOS Sleep Cohort, which is comprised of 2,846 men with comprehensive and objective measures of sleep and for whom first void morning urine, has been collected for melatonin analyses, along with serum for vitamin D analyses. We will investigate associations between urinary melatonin levels and risk of mortality, using a full cohort approach. We will further examine the association between melatonin levels and a variety of aging-related conditions such as sleep disturbance, cognitive impairment and poor physical function, making use of repeat measures for these traits. Finally, we will assess the role of vitamin D in these associations. We expect 528 deaths to accrue during the course of follow-up. The results from this study will, for the first time, prospectively examine the interplay between variations in melatonin levels, morbidity and mortality among elderly men. Our findings could help identify individuals who are more prone to sleep problems and other age-related conditions, based on their melatonin concentrations. This research has important implications for the longevity and quality of life of the rapidly growing population of elderly in America as it may lay the groundwork for future intervention studies of melatonin and its influence on sleep characteristics, cognitive and physical function, and, ultimately, mortality. PUBLIC HEALTH RELEVANCE: In search of new factors that may contribute to healthy longevity in our rapidly aging society, we propose to evaluate the effects of three interrelated, phylogenetically ancient pathways on age-related disorders and mortality: sleep, melatonin, and the vitamin D axis. We will use existing resources from 2,846 participants of the ongoing MrOS Sleep Study. If successful, our study could lay the groundwork for a melatonin trial for healthy aging in the elderly.

描述（由申请人提供）：有越来越多的证据表明睡眠障碍，昼夜节律系统与寿命之间存在关联。尽管这种生理学基本上仍然是推测性的，但研究表明，褪黑激素可能是睡眠障碍与死亡率之间的可能联系。褪黑激素是一种与人类昼夜节律系统密切相关的癌症保护激素，已经通过实验研究与寿命有关，但迄今为止尚未对人类进行研究。此外，对与褪黑激素相关的因素（包括褪黑激素与睡眠特征的关系）知之甚少。维生素D为了创造其必要的阳光，似乎可以降低死亡率，并已证明会降低老年人的骨折风险。从未研究过褪黑激素和维生素D对光的敏锐敏感，从未研究过。我们将评估一群老年人队列中的睡眠特征，褪黑激素和寿命之间的关系。我们将利用MROS Main队列的亚属MROS睡眠队列，由2,846名男性组成，具有全面和客观的睡眠度量，并为其首先为之植入了早晨尿液，用于褪黑激素分析，以及维生素D分析的血清。我们将使用完整的队列方法调查尿素素水平与死亡风险之间的关联。我们将进一步研究褪黑激素水平与各种与衰老相关的疾病之间的关联，例如睡眠障碍，认知障碍和身体机能不佳，利用了这些特征的重复度量。最后，我们将评估维生素D在这些关联中的作用。我们预计在随访过程中会造成528人死亡。这项研究的结果将首次前瞻性地检查褪黑激素水平的变化，老年男性的发病率和死亡率之间的相互作用。我们的发现可以帮助识别那些基于褪黑激素的浓度更容易患睡眠问题和其他与年龄有关的人。这项研究对美国迅速增长的老年人人口的寿命和生活质量具有重要意义，因为它可能为褪黑激素的未来干预研究及其对睡眠特征，认知和身体机能的影响奠定基础，并最终是死亡率。 公共卫生相关性：为了寻找可能导致健康衰老社会健康寿命的新因素，我们建议评估三种相互关联的，系统发育上古老的途径对年龄相关疾病和死亡率的影响：睡眠，褪黑激素和维生素D轴。我们将使用正在进行的MROS睡眠研究的2,846名参与者中的现有资源。如果成功的话，我们的研究可能为老年人健康衰老的褪黑激素试验奠定基础。