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.
|Liang, Pei; Henning, Susanne M; Guan, Johnny et al. (2018) Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer. J Natl Cancer Inst :|
|Qin, Qing; Mehta, Hemal; Yen, Kelvin et al. (2018) Chronic treatment with the mitochondrial peptide humanin prevents age-related myocardial fibrosis in mice. Am J Physiol Heart Circ Physiol 315:H1127-H1136|
|Yen, Kelvin; Wan, Junxiang; Mehta, Hemal H et al. (2018) Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Sci Rep 8:14212|
|Henning, Susanne M; Galet, Colette; Gollapudi, Kiran et al. (2018) Phase II prospective randomized trial of weight loss prior to radical prostatectomy. Prostate Cancer Prostatic Dis 21:212-220|
|Mao, Kai; Quipildor, Gabriela Farias; Tabrizian, Tahmineh et al. (2018) Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun 9:2394|
|Kim, Su-Jeong; Mehta, Hemal H; Wan, Junxiang et al. (2018) Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY) 10:1239-1256|
|Xiao, Jialin; Cohen, Pinchas; Stern, Mariana Carla et al. (2018) Mitochondrial biology and prostate cancer ethnic disparity. Carcinogenesis 39:1311-1319|
|Nencioni, Alessio; Caffa, Irene; Cortellino, Salvatore et al. (2018) Fasting and cancer: molecular mechanisms and clinical application. Nat Rev Cancer 18:707-719|
|Nashine, Sonali; Cohen, Pinchas; Nesburn, Anthony B et al. (2018) Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration. Sci Rep 8:15175|
|Guidi, Novella; Longo, Valter D (2018) Periodic fasting starves cisplatin-resistant cancers to death. EMBO J 37:|