Association of urinary melatonin levels and aging-related outcomes in older men.
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.



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.



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.



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).



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.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, USA. Electronic address: nheed@channing.harvard.edu.
Elizabeth E
EE
Devore
California Pacific Medical Center Research Institute, USA.
Stephanie L
SL
Harrison
California Pacific Medical Center Research Institute, USA.
Katie L
KL
Stone
Department of Health Studies, Center for Behavioral Neuroscience, American University, USA.
Kathleen F
KF
Holton
Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, USA.
Elizabeth
E
Barrett-Connor
Department of Psychiatry, University of California San Diego, USA; Department of Medicine, University of California San Diego, USA.
Sonia
S
Ancoli-Israel
Department of Psychiatry, University of California San Francisco, USA; Department of Neurology, University of California San Francisco, USA; Department of Epidemiology, University of California San Francisco, USA.
Kristine
K
Yaffe
Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, USA; Department of Medicine, University of Minnesota, USA; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, USA.
Kristine
K
Ensrud
California Pacific Medical Center Research Institute, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, USA.
Peggy M
PM
Cawthon
Departments of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, and Harvard Medical School, USA.
Susan
S
Redline
Oregon Clinical and Translational Research Institute and School of Medicine, Oregon Health and Science University, USA.
Eric
E
Orwoll
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, USA; Department of Epidemiology, H.T. Chan Harvard School of Public Health, USA; Department of Epidemiology, Center for Public Health, Medical University of Vienna, Austria.
Eva S
ES
Schernhammer
D000368:Aged; D000375:Aging / Q000502:physiology / Q000652:urine*; D002318:Cardiovascular Diseases / Q000401:mortality; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000502:physiology / Q000652:urine*; D009026:Mortality; D010809:Physical Fitness / Q000502:physiology
C054513:6-sulfatoxymelatonin; D008550:Melatonin
Aging; Cognitive function; Melatonin; Mortality; Physical function
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