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.