Lifespan 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, statistical and information resources necessary to enable a systems-wide approach to understanding healthy aging. The JAX NSC has transformed aging research at JAX, providing central resources to support our investigators that have resulted in 38 peer-reviewed publications and several active grants in the last funding period. The Center has developed nascent regional and national resources for aging research, including genetic maps, novel statistical methods and aging mouse resources and tissues that support our numerous collaborations and external researchers. All JAX NSC data 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 are readily available to the aging research community. In this renewal, we will advance toward our goal by providing next-generation resources and support to aging investigators while leveraging JAX's unparalleled expertise in the large-scale identification and functional validation of complex polygenic traits i mice.
Our Specific Aims are to: 1) Increase the diversity of mouse resources available for aging research, including a new large-scale intervention study to investigate gene-diet interactions in genetically diverse mouse populations; 2) Strengthen statistical tools and support available to the aging community; 3) Expand the use of genetic approaches to translational research in aging, namely through a robust screening pipeline for candidate human aging genes; 4) Expand the research focus on aging, healthspan and age-related diseases at JAX through a robust Research Development Core; and 5) Provide effective Center administration and enhance the utility of JAX NSC resources throughout the aging community. The Center will be led by a highly experienced team of Principal Investigators and Core Leaders who, together with JAX NSC members and with oversight from an External Advisory Board, will provide effective management to facilitate the goals and objectives of the Center. The Center will also leverage the 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 identify genetic differences and probe their role in controlling healthy aging. 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 |
Showing the most recent 10 out of 48 publications
