The Mouse Models Core (Core B) will be responsible for providing the investigators of this Program Project with the tissues and cells necessary to achieve their experimental aims. Experiments in this Program Project focus on mice, both naturally aged mice and a unique strain of mice engineered to age rapidly, which will accelerate the pace of research. Novel strains of double mutant mice, reporter mice, and mice with accelerated aging of one tissue at a time will be bred to address the overarching question- does stochastic, endogenous damage promote aging via a cell autonomous or non-autonomous mechanism? In addition to the genetic approaches, treatment studies will be conducted on mice in Core B to test specific hypotheses about the contribution of oxidative stress, signaling pathways and adult stem cell attrition to aging. By coordinating the creation of animal cohorts and exposure studies within this Core, it will be possible to standardize methods and quality control, which will improve the reproducibility of in vivo experiments, minimize animal use and costs, and dramatically improve the sensitivity of analytical approaches to quantify aging (e.g. histopathology and proteomics). In addition, this centralized Core supports an integrated systems biology approach to the study of aging because all of the following information will be obtained for each animal studied via sharing specimens with each ofthe other projects and cores: Vital statistics, age at onset of aging-related symptoms, organ dysfunction and histopathology: Core B Level of ROS, mitochondrial function, cell death and senescence, identification of cell types affected: Core C Level of oxidative DNA damage: Project 1 Activation of NF-kB and signaling in response to cellular damage and inflammation: Project 2 Adult stem cell function: Project 3

Public Health Relevance

The Mouse Models Core of this Program Project will foster research in animal models of accelerated and natural aging aimed at elucidating the basic biochemical, genetic and physiological mechanisms underlying aging and age-related degenerative changes in mammals, which is directly in-line with the mission ofthe Division of Aging Biology ofthe National Institute of Aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-2 (M2))
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Scripps Research Institute
La Jolla
United States
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Niedernhofer, L J; Kirkland, J L; Ladiges, W (2016) Molecular pathology endpoints useful for aging studies. Ageing Res Rev :
Robbins, Paul D; Dorronsoro, Akaitz; Booker, Cori N (2016) Regulation of chronic inflammatory and immune processes by extracellular vesicles. J Clin Invest 126:1173-80
Zhang, Changqing; Ferrari, Ricardo; Beezhold, Kevin et al. (2016) Arsenic Promotes NF-Κb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function. Stem Cells 34:732-42
Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael et al. (2016) Metabolic drift in the aging brain. Aging (Albany NY) 8:1000-20
Zhu, Yi; Tchkonia, Tamara; Fuhrmann-Stroissnigg, Heike et al. (2016) Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15:428-35
Flores, Rafael R; Kim, Eun; Zhou, Liqiao et al. (2015) IL-Y, a synthetic member of the IL-12 cytokine family, suppresses the development of type 1 diabetes in NOD mice. Eur J Immunol 45:3114-25
Wallace, Callen T; St Croix, Claudette M; Watkins, Simon C (2015) Data management and archiving in a large microscopy-and-imaging, multi-user facility: Problems and solutions. Mol Reprod Dev 82:630-4
Kelley, Eric E (2015) Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase. Arch Toxicol 89:1193-207
Reay, Daniel P; Bastacky, Sheldon I; Wack, Kathryn E et al. (2015) D-Amino Acid Substitution of Peptide-Mediated NF-κB Suppression in mdx Mice Preserves Therapeutic Benefit in Skeletal Muscle, but Causes Kidney Toxicity. Mol Med 21:442-52
Mu, Xiaodong; Tang, Ying; Lu, Aiping et al. (2015) The role of Notch signaling in muscle progenitor cell depletion and the rapid onset of histopathology in muscular dystrophy. Hum Mol Genet 24:2923-37

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