Devore Elizabeth E, Harrison Stephanie L, Stone Katie L, Holton Kathleen F, Barrett-Connor Elizabeth, Ancoli-Israel Sonia, Yaffe Kristine, Ensrud Kristine, Cawthon Peggy M, Redline Susan, Orwoll Eric, Schernhammer Eva S
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, USA.
California Pacific Medical Center Research Institute, USA.
Sleep Med. 2016 Jul;23:73-80. doi: 10.1016/j.sleep.2016.07.006. Epub 2016 Aug 4.
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.
昼夜节律紊乱会加速衰老，且昼夜节律系统调节认知和身体功能；因此，昼夜节律标志物（如褪黑素）可能与健康衰老和长寿的关键方面相关。
在男性骨质疏松性骨折研究中的2821名老年男性中，评估尿褪黑素水平与认知功能、身体功能及死亡率之间的关系。
队列研究。
2003年至2005年，参与者提供首次晨尿样本，检测其中6-硫酸氧褪黑素（尿中主要的褪黑素代谢产物）；认知和身体功能评估在基线时及平均6.5年后进行了两次。通过对死亡证明的中央审查确认参与者的死亡情况，随访平均9.2年。
在多变量调整回归模型中，我们观察到随着褪黑素四分位数增加，基线时数字警觉测试得分（即完成时间减少）有显著的改善趋势（P趋势=0.01）；然而，比较极端四分位数时，平均完成时间得分无显著差异（组均值：547.1秒（95%可信区间：533.6，560.6）对561.3秒（95%可信区间：547.8，574.9）），且尿褪黑素水平与其他认知测试得分或随时间的任何认知变化得分均无关联。此外，褪黑素水平与身体功能得分（完全调整模型中步行速度的P趋势=0.4，从椅子上站起的P趋势=0.7，握力的P趋势=0.6）或死亡风险（完全调整模型中P趋势=0.3）无关。
在这组老年男性中，我们几乎没有发现尿褪黑素水平与健康衰老和死亡率的关键指标之间存在关联的证据。进一步的研究应探讨褪黑素，特别是在生命早期进行评估时，以及其他昼夜节律标志物与健康衰老结果之间的关系。
