Healthspan is a complex trait, influenced by many interacting polymorphic alleles and environmental factors that may accelerate or delay aging, reduce or increase disease risk, and/or promote extended lifespan. Thus, assessing the role of genetic variation in aging requires an experimental strategy capable of modeling the genetic and biological complexity of human populations while allowing for efficient identification and validation of candidate genes. With this proposal, the JAX NSC seeks support to further develop and disseminate the next generation of genetic, phenotyping, and information resources necessary to enable a systems-wide approach to understanding healthy aging. Over the past 15 years, The JAX NSC has transformed aging research both at JAX and across the geroscience community, providing central resources to support investigators that have resulted in 26 peer-reviewed publications in the last funding period. The Center has developed nascent regional and national resources for aging research, including aging mouse resources and tissues that support our numerous collaborations and external researchers. All JAX NSC data and tools are publicly disseminated on the Mouse Phenome Database and the JAX NSC website, thus ensuring that the resources generated and expertise acquired through the Center is readily available to the aging research community. In this renewal, we will advance towards our goal by providing unique resources, tools, and support to geroscience investigators while leveraging JAX's unparalleled expertise in the large-scale identification and functional validation of complex polygenic traits in mice. We will do this by providing effective Center administration and enhancing the utility of JAX NSC resources throughout the aging community (Aim 1); expanding the research focus on aging, healthspan and age-related diseases through a robust Research Development Core (Aim 2); increasing the diversity of mouse resources available for aging research, including a new study to, for the first time, investigate the effect of genetic variation on cellular senescence and treatment with senolytic drugs (Aim 3); strengthening the data and computational and support available to the aging community (Aim 4); expanding the use of machine learning technologies in interpretation of aging pathologies (Aim 5). The Center will be led by a highly experienced team of Principal Investigators and Core Leaders who, with oversight from an External Advisory Board, will provide effective management to facilitate the goals and objectives of the Center. The Center will leverage unparalleled institutional resources, facilities and expertise of The Jackson Laboratory, a globally renowned institution for mouse genetics research, to enhance its goals and the utility of the resources it generates for the aging research community.
Human aging is influenced by genetic factors, whereby differences in longevity as well as changes in health and disease risk with time are linked to variation in individuals' genetic codes. The Jackson Laboratory Nathan Shock Center will develop resources to encourage the use of a wider range of mouse models in aging research. Resources?including aged mouse models that mirror human genetic variation, metabolic and microbiome data, and methods to reveal genetic factors tied to human aging?will be available to the scientific community, accelerating research to understand and ultimately prolong healthy human aging.
| Thompson, Michael J; Chwia?kowska, Karolina; Rubbi, Liudmilla et al. (2018) A multi-tissue full lifespan epigenetic clock for mice. Aging (Albany NY) 10:2832-2854 |
| Backer, Grant; Eddy, Sean; Sheehan, Susan M et al. (2018) FAR2 is associated with kidney disease in mice and humans. Physiol Genomics 50:543-552 |
| Sutphin, George L; Backer, Grant; Sheehan, Susan et al. (2017) Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity. Aging Cell 16:672-682 |
| Lee, Benjamin P; Buri?, Ivana; George-Pandeth, Anupriya et al. (2017) MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice. Sci Rep 7:44620 |
| Sutphin, George L; Mahoney, J Matthew; Sheppard, Keith et al. (2016) WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning. PLoS Comput Biol 12:e1005182 |
| Korstanje, Ron; Deutsch, Konstantin; Bolanos-Palmieri, Patricia et al. (2016) Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria. J Am Soc Nephrol 27:3271-3277 |
| Bogue, Molly A; Peters, Luanne L; Paigen, Beverly et al. (2016) Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span. J Gerontol A Biol Sci Med Sci 71:170-7 |
| Didion, John P; Morgan, Andrew P; Yadgary, Liran et al. (2016) R2d2 Drives Selfish Sweeps in the House Mouse. Mol Biol Evol 33:1381-95 |
| Young, Kira; Borikar, Sneha; Bell, Rebecca et al. (2016) Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging. J Exp Med 213:2259-2267 |
| Schoenrock, Sarah Adams; Oreper, Daniel; Young, Nancy et al. (2016) Ovariectomy results in inbred strain-specific increases in anxiety-like behavior in mice. Physiol Behav 167:404-412 |
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