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. [unreadable] [unreadable] [unreadable] [unreadable]