Background Circadian disruptions can contribute to accelerated aging, and the circadian system regulates cognitive and physical functions; therefore, circadian markers (eg, melatonin) may be associated with key aspects of healthy aging and longevity. Objective To evaluate urinary melatonin levels in relation to cognitive function, physical function, and mortality among 2,821 older men in the Osteoporotic Fractures in Men Study Design Cohort study. Measurements In 2003–2005, participants provided first-morning spot urine samples, which were assayed for 6-sulfatoxymelatonin (the primary melatonin metabolite in urine); cognitive and physical function assessments were completed twice, at baseline and an average of 6.5 years later. Participant deaths were confirmed by central review of death certificates over a mean of 9.2 years of follow up. Results In multivariable-adjusted regression models, we observed a significant trend of better Digit Vigilance Test scores (ie, decreased time to completion) at baseline across increasing melatonin quartiles (p-trend = 0.01); however, mean time-to-completion scores did not significantly differ comparing extreme quartiles (group means: 547.1 seconds (95% CI: 533.6, 560.6) versus 561.3 seconds (95% CI: 547.8, 574.9)), and there were no associations of urinary melatonin levels with other cognitive test scores, or any cognitive change scores over time. Furthermore, melatonin levels were not related to physical function scores (p-trends = 0.4 for walking speed, 0.7 for chair stands, and 0.6 for grip strength in fully-adjusted models) or mortality risk (p-trend = 0.3 in the fully-adjusted model). Conclusion We found little evidence of associations between urinary melatonin levels and key measures of healthy aging and mortality in this cohort of older men. Further research should explore the relation of melatonin, particularly if assessed earlier in life, and other circadian markers with healthy aging outcomes.
Bibliographical noteFunding Information:
The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA) (grant numbers U01 AG027810 , U01 AG042124 , U01 AG042139 , U01 AG042140 , U01 AG042143 , U01 AG042145 , U01 AG042168 ), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (grant number U01 AR066160 ), the National Center for Advancing Translational Sciences (NCATS) (grant number UL1 TR000128 ), and NIH Roadmap for Medical Research. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study under the following grant numbers: R01 HL071194 , R01 HL070848 , R01 HL070847 , R01 HL070842 , R01 HL070841 , R01 HL070837 , R01 HL070838 , and R01 HL070839 . The National Institute on Aging (NIA) provided funding for the work presented in the current paper under R01 AG030089 . The sponsor played no role in the study design; the collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit this manuscript for publication.
- Cognitive function
- Physical function