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

描述(由申请人提供)：越来越多的证据表明睡眠障碍、昼夜节律系统和长寿之间存在联系。尽管这在很大程度上仍是一种推测，但研究表明，褪黑素可能是睡眠障碍和死亡率之间的一个可能联系。褪黑素是一种防癌激素，与人类的昼夜节律系统密切相关，实验研究表明褪黑素与长寿有关，但到目前为止还没有对人类进行研究。此外，人们对褪黑素的相关因素知之甚少，包括褪黑素与睡眠特征的关系。维生素D的产生需要阳光，它似乎可以降低死亡率，并已被证明可以降低老年人骨折的风险。褪黑素和维生素D都对光非常敏感，但它们是如何相互联系的，还从未被研究过。我们将在一组预期的老年男性队列中评估睡眠特征、褪黑素和寿命之间的关系。我们将利用MROS主要队列中的一个子队列，即MROS睡眠队列，该队列由2846名男性组成，他们对睡眠进行了全面和客观的测量，并收集了第一次排空的晨尿，用于褪黑激素分析，以及用于维生素D分析的血清。我们将使用全队列方法调查尿褪黑素水平与死亡风险之间的关系。我们将利用对这些特征的重复测量，进一步研究褪黑素水平与各种与衰老相关的疾病之间的联系，如睡眠障碍、认知障碍和身体功能低下。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将有528人死亡。这项研究的结果将首次前瞻性地检验老年男性褪黑素水平变化、发病率和死亡率之间的相互作用。根据褪黑素的浓度，我们的发现可能有助于识别更容易出现睡眠问题和其他与年龄相关的疾病的人。这项研究对美国快速增长的老年人口的寿命和生活质量具有重要意义，因为它可能为未来褪黑素的干预研究奠定基础，以及它对睡眠特征、认知和身体功能的影响，最终导致死亡率。公共卫生相关性：在我们快速老龄化的社会中，为了寻找可能有助于健康长寿的新因素，我们建议评估三条相互关联的、在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、褪黑素和维生素D轴。我们将使用正在进行的MROS睡眠研究的2846名参与者的现有资源。如果成功，我们的研究可能为褪黑素在老年人中的健康衰老试验奠定基础。

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.