This project is directed at changes in the sleep-promoting system with age. The investigator is an established investigator who is beginning a new line of investigation into the changes with age in molecular mechanisms that promote sleep. Sleep is thought to be determined by the interaction between two processes-the circadian process and the sleep- promoting process. The later (process S) increases in relationship to the duration of prior wakefulness. There is considerable evidence that the strength of this sleep-promoting process declines with age. Changes in this may, at least in part, play an important role in the high prevalence of insomnia in the elderly. Sleep promotion is thought to be the result of accumulation during wakefulness of molecules that promote sleep. Among such molecules, cytokines have a prominent role. Both interleukin-1 (IL-1) and tumor necrosis factor (TNF) enhances sleep and increases in the levels of these molecules and their mRNA occur with sleep deprivation. Currently we do not know, however, whether changes in this sleep-promoting system occur with age. Thus, one of the goals of our studies is to determine, as we predict, the increase in IL-1 and TNF with sleep deprivation is less in older as compared to younger rates in relevant brain regions. It is unlikely, however, that IL-1 and TNF are the only cytokines involved. There is powerful positive feedback between these prototypical """"""""pro-inflammatory"""""""" cytokines. Thus, there must be other counter-regulating cytokines involved. We predict that IL-4, IL-10 and IL-13, and possibly IL-16, will be unregulated in relevant brain regions with sleep deprivation and act to limit the increases in IL-1 and TNF. We will determine whether this is so. Thus, this pilot project is designed to assess whether changes in cytokine response to sleep deprivation occur with age and to assess more globally the various cytokines that are involved. The results of this pilot project will allow us, in the future a more in-depth study of changes in the brain cytokine response to sleep deprivation.
