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（改编自研究者摘要）：研究者的 实验室最近观察到了 两个老年志愿者样本的昼夜节律阶段。 的受试者 平均年龄在70岁左右，几乎一半的人有6-硫酸氧褪黑激素分泌 完全超出健康年轻人的正常范围。 此外，委员会认为， 观察到的相位异常与客观睡眠密切相关 破坏 观察到的昼夜节律定时的紊乱是如此 严重到与夜班或时差反应相当 从尼泊尔抵达后。 如此可怕的昼夜节律不同步，如果 经验证，可以为失眠提供主要因果解释， 抑郁症状在美国老年人中非常普遍。 验证 老年志愿者的昼夜节律紊乱， 将测量唾液和血液褪黑激素的昼夜节律， 尿中褪黑激素的6-硫酸氧代谢产物，并辅以措施 在70名60岁的志愿者中， 年加。 3天超短睡眠-觉醒周期将用于 昼夜节律相位测量，然后是海拔 褪黑激素受损表明可能存在同步性阻力 被强光压制。 将采用以下方法检查重测稳定性： 在实验室和室内对30名老年志愿者进行重复观察 医院CRC。 将评估20名健康对照（年龄20-40岁）， 用同样的方法确定昼夜节律相位的正常范围。 如果 证实了与衰老相关的昼夜节律相位不同步 通常足以导致失眠和抑郁，纠正这些 相位异常可能是缓解抑郁的重要途径 这是许多美国老年人所遭受的。