Challenges to the processes of sleep-wake cycle regulation in aging

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Between the ages of 20 and 60, increasing age is associated with less time asleep, more awakenings during sleep, less deep sleep, and more lighter stages of sleep. The long term goal of our program is to understand the mechanisms that underlie age-related changes of the sleep-wake cycle. The quality of sleep and vigilance is controlled by the interaction between the homeostatic process (number of hours of wakefulness) and the circadian process (signal from the biological clock). Aging may have a negative impact on these processes individually or when they interact.  Our approach is to evaluate the contribution of age to the effects of challenges put on homeostatic and circadian processes. Specifically, we will evaluate age-related effects of pharmacological manipulations associated to sleep homeostasis. We have selected caffeine because it is an antagonist of a neuromodulator closely related to sleep homeostasis (adenosine). Objectives are: (1) To perform a dose-response curve of manipulations of sleep homeostasis in aging. We will evaluate the effects of three doses of caffeine in young and older subjects. We expect age-related differences to be enhanced following higher doses.We will also evaluate the impact of habitual caffeine consumption on age-related effects of caffeine. We expect age-related differences to be more pronounced in low caffeine consumers than in high consumers. (2) To assess how interactions between homeostatic and circadian processes modulate the ability to sleep/stay awake in aging. We will compare age-related effects of caffeine at different times of day as well as when submitted to a shift in the timing of the sleep-wake cycle (like in jet-lag). We expect caffeine's effects and age-related differences to be more prominent when the sleep-wake cycle occurs at an abnormal time of day. (3) To evaluate the consequences on vigilance of an attenuation of homeostatic sleep drive in aging. We will evaluate the "indirect" effects of caffeine on vigilance through its detrimental effects on sleep in older and younger subjects. We expect indirect effects to be more prominent when sleep is more affected (i.e. abnormal timing, older subjects). This program will privide important cues on how aging modifies the sleep-wake cycle.