Project Summary Sirtuin 1 has been implicated in multiple functions is thought as one of the candidate molecules for promoting healthy aging, because of its neuroprotective roles against several age-related pathologies, and several studies done in animals showed an association between sirtuin 1 and lifespan elongation. Sirtuin 1 has been shown to impact several brain disorders such as neurodegenerative disorders, such as Alzheimer’s disease. Therefore, it is important to have a tool for non-invasive measurement of sirtuin 1 expression and function in vivo, and PET imaging would be an ideal tool. Unfortunately, to date, there are no suitable non-invasive neuroimaging tools for investigating these processes in animals or in man until we developed the first PET imaging probe for sirtuin 1 recently. The development of techniques for visualizing sirtuin 1 in vivo represents a key step in understanding both the normal function and pathophysiology of sirtuin 1 in brain. Moreover, these techniques these techniques will accelerate the discovery/development of small molecule therapeutics that selectively interacts with sirtuin 1. The project is aimed to measure the expression of sirtuin 1 in brain of Alzheimer’s Disease animal model and wild-type mice over age, using our novel PET imaging probe, [11C]CWL-1, prior to first-in-human imaging.