Our group demonstrated that a continuous isocaloric Ketogenic diet extends cognitive function, memory and longevity and physical function in C57BL6 mice (Roberts et al. 2017). The overall concept is in Project 1 to test the KD mechanism and 'ketodrug' molecules that might reconstruct these KD benefits (PI: Cortopassi). In Project 2, the goal is to understand the epigenetic mechanism of aging and the extent to which KD and ketodrugs reverse this mechanism (PI: Pelicci). In Project 3, the goal is to understand the extent to which the muscle benefit(s) of the KD provide an additional benefit in the aging and AD brain (PI: Baar). In Project 4, the main goal is to determine whether and the extent to which an intermittent KD could provide the same benefits to cognition and memory and AD as the continuous KD (PI: Ramsey). Core A provides administrative support, monthly PPG and yearly EAC support (CL: Cortopassi). Core B provides expert biostatistical support in experimental design and analysis (CL: Kim). Core C provides animal services to all 4 Projects, including technical support in Alzheimer's disease pathophysiological analysis (CL: Lloyd).