VERIFICATION OF CIRCADIAN ABNORMALITIES IN AGING

验证衰老过程中的昼夜节律异常

• 批准号: 6372212
• 负责人: DANIEL Frederick KRIPKE
• 金额: $ 44.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6372212
• 关键词: aging; blood chemistry; body temperature; circadian rhythms; clinical research; cortisol; depression; human middle age (35-64); human old age (65+); human subject; lighting; melatonin; photostimulus; saliva; sleep; sleep disorders; urinalysis; wakefulness; young adult human (21-34)

DESCRIPTION (adapted from investigator's abstract): The investigator's laboratory has recently observed extraordinary malsynchronization of circadian rhythm phases in two samples of aging volunteers. Of subjects averaging about age 70, almost half had 6-sulphatoxymelatonin excretion phases wholly outside the normal range for healthy young adults. Moreover, the observed phase abnormalities were well-correlated with objective sleep disruption. The disturbances of circadian rhythm timing observed were so severe as to be comparable to effects of graveyard shiftwork or jet lag after arrival from Nepal. Such appalling circadian malsynchronization, if verified, could provide the main causal explanation for the insomnia and depressive symptoms so highly prevalent among aging Americans. To verify the derangement of circadian rhythms among aging volunteers, this project will measure circadian rhythms in salivary and blood melatonin as well as the urinary 6-sulphatoxy metabolite of melatonin, supplemented by measures of urinary cortisol and temperature, in a sample of 70 volunteers ages 60 years plus. A 3-day ultra-short sleep-wake cycle will be used for round-the-clock circadian phase measurement, followed by elevation of the possible synchronization resistance as indicated by impaired melatonin suppression by bright light. Test-retest stability will be examined with repeat observations of 30 aging volunteers in the laboratory and in the hospital CRC. Twenty healthy controls (ages 20-40) will be assessed to establish with the same methods the normal ranges for circadian phase. If it is verified that circadian phase malsynchronization associated with aging is commonly sufficient to cause insomnia and depression, correcting these phase abnormalities might be an important approach to relieve the distress which so many aging Americans suffer.

描述（根据调查员的摘要改编）：调查员的 实验室最近观察到了非凡的Malsngronation 昼夜节律阶段在两个老化志愿者的样本中。 主题 平均大约70岁，几乎一半有6-磺氧蛋白素排泄物 对于健康的年轻人来说，完全超出了正常范围。 而且， 观察到的相异常与客观睡眠相关 破坏。 观察到的昼夜节律时间的干扰是如此 严重以与墓地变速器或喷气滞后的影响相媲美 从尼泊尔抵达后。 这样令人震惊 经过验证，可以为失眠和 抑郁症状在老年人中非常普遍。 验证 在老龄化志愿者中，昼夜节律的危险，这个项目 将测量唾液和血液褪黑激素的昼夜节律以及 褪黑激素的尿6-硫酸代谢产物，补充了措施 尿皮质醇和温度，在70名60岁的志愿者样本中 多年。 为期3天的超短期睡眠觉醒周期将用于 全天候昼夜节相测量，然后升高 如褪黑激素受损所示，可能的同步电阻 明亮的光线抑制。 测试重测的稳定性将进行检查 在实验室和 医院CRC。 将评估二十个健康对照（20-40岁） 用相同的方法建立昼夜节相的正常范围。 如果 可以验证昼夜节相倾斜度与衰老相关 通常足以引起失眠和抑郁，纠正这些 阶段异常可能是缓解困扰的重要方法 这么多老化的美国人受苦。