DISRUPTED SLEEP IN THE ELDERLY: CIRCADIAN ETIOLOGY

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It is generally appreciated that sleep-wake habits change with age. The most consistent such change is the advance of the sleep period to earlier bedtimes and earlier arising times. In addition, older individuals often report an "assymmetric" disruption of sleep, consistent with a shift of the underlying rhythm controlling sleep to an earlier time of day. Similar changes in the circadian rhythms of REM sleep and body temperature support the central hypothesis that the phase of the circadian system advances to an earlier time with increased age. On the basis of simulations using the "dual-oscillator" model of human circadian rhythms, three testable hypotheses are proposed: 1) that the phase advance of sleep reflects an underlying phase advance of the "deep" circadian oscillator; 2) that this phase advance under entrained conditions is a consequence of an age-dependent decrease in the free-running period of the deep oscillator; and 3) that amplification of normal entraining stimuli can reverse this phase advance and the consequent sleep disturbance. A series of experiments are proposed utilizing new methodologies that allow direct measurement of deep oscillator phase and period. These experiments will accomplish four specific aims: 1) quantification of an age-dependent change in circadian phase; 2) documentation of its role as the pathophysiologic mechanism in a subset of age-related sleep disturbances; 3) elucidation of the mechanism underlying the altered phase relations, and; 4) evaluation of a potential non-drug therapy for age-related sleep disruption. This work has significant implications for circadian oscillator theory as well as for gerontologic medicine. Age-related changes in the circadian system have been etiologically implicated in the increased prevalence of depression and disorders of etiologically implicated in the increased prevalence of depression and disorders of thermoregulation (hypothermia) among the aged. Greater understanding of circadian mechanisms and their age-dependent alteration, as well as the development of non-invasive methods for reversing this alteration, offer substantive promise for improved health of the elderly.