VERIFICATION OF CIRCADIAN ABNORMALITIES IN AGING

University Of California San Diego, La Jolla CA

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Abstract

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.