Abstract The Animal and Biostatistics Core will work directly with Project Leaders to design, plan, monitor and interpret all animal experiments, as well as, provide specific mouse models and standardized experimental protocols in support of the overall program's common goals: 1) understand how age and genetic background modulate the effects of fasting-mimicking diets (FMD) and protein restriction cycles (PRC) on longevity and healthspan, 2) study the mechanisms of FMD-, PRC-dependent cellular protection, regeneration and rejuvenation in the hematopoietic and nervous systems, 3) understand the link between FMD and PRC, GH-IGF-1, mTOR and humanin to test the hypothesis that this mitochondrial peptide is a PFC/PRC mediator with the potential to serve as a fasting/protein restriction mimetic, 4) study the regulation of the cysteine gamma lyase-dependent production of the gas H2S, negatively regulated by GH/IGF-1-mTOR, and test the hypothesis that H2S is a mediator of the protective effects of FMD on resistance to hepatic ischemia reperfusion injury and chemotherapy-induced toxicity to hematopoietic stem cells. The core provides an integrative framework for assessment of common outcomes across the individual projects needs. Aim 1. Design, plan and monitor animal experimental procedures as directed by Project Leaders. Studies are designed to achieve sufficient power/sensitivity to meet the stated objectives. All experimental procedures performed on mice are standardized and performed by Core B to ensure consistent assessment across all projects. These include: A) Longevity, B) Healthspan (Metabolic/Cognitive and Cellular/Molecular), C) Stress resistance and Mechanistic studies, D) Tissue collection/distribution. Aim 2. Coordinate animal use for program. All animals obtained or generated through Core B will be housed in the state-of-the-art vivarium facility in the Ray R Irani Hall at USC. Individual dedicated animal holding rooms for the exclusive use of either breeding, longevity or stress resistance will ensure consistency of biological environment, noise control and security across all studies.