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关联。虽然这在生理上很大程度上仍然是推测性的，但研究表明褪黑激素可能是睡眠障碍和死亡率之间的一种可能联系。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，实验研究表明褪黑激素与长寿有关，但迄今为止还没有进行过人体研究。此外，对褪黑激素相关因素知之甚少，包括褪黑激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。褪黑激素和维生素D都对光非常敏感，它们是如何相互联系的，这一点从未被研究过。我们将在一个前瞻性的老年男性队列中评估睡眠特征、褪黑激素和长寿之间的关系。我们将使用MrOS主要队列的子队列，MrOS睡眠队列，其由2，846名具有全面和客观睡眠测量的男性组成，并且已经收集了他们的首次晨尿用于褪黑激素分析，沿着血清用于维生素D分析。我们将使用全队列方法研究尿褪黑激素水平与死亡风险之间的关系。我们将进一步研究褪黑激素水平与各种衰老相关疾病之间的关联，如睡眠障碍，认知障碍和身体功能差，利用这些特征的重复测量。最后，我们将评估维生素D在这些协会中的作用。我们预计在随访过程中将增加528例死亡。这项研究的结果将首次前瞻性地研究老年男性褪黑激素水平变化、发病率和死亡率之间的相互作用。我们的研究结果可以帮助确定谁更容易出现睡眠问题和其他与年龄有关的条件，根据他们的褪黑激素浓度。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影响，因为它可能为未来褪黑激素的干预研究及其对睡眠特征、认知和身体功能以及最终的影响奠定基础。死亡率。 公共卫生相关性：为了寻找可能有助于我们快速老龄化社会健康长寿的新因素，我们建议评估三个相互关联的、遗传学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。我们将使用来自正在进行的MrOS睡眠研究的2，846名参与者的现有资源。如果成功，我们的研究可以为老年人健康衰老的褪黑激素试验奠定基础。

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.