The Translational Core of The Jackson Laboratory Nathan Shock Center (JAX NSC) develops and provides resources for the other NSCs and the aging community to aid in comparative and translational aging research. We are developing a pipeline that allows for efficient screening and prioritization of candidate genes identified in human studies, first in C.elegans then followed by mouse models. Preliminary studies for the different parts of the pipeline show their effectiveness and we have successfully tested a set of 149 genes in C.elegans, which were identified in human studies as being associated with aging. Knockdown showed a significant difference in lifespan for 65% of the genes. Novel mouse models were developed for two of these genes and are currently in lifespan studies. Preliminary data shows significant differences in these models compared to wildtype animals for several age-related traits. To enable this pipeline and make it available as a resource to the aging community, the specific aims of the Translational Core are to:
Aim 1. Identify the most promising candidate genes associated with human aging and age-related phenotypes from the Framingham Heart Study and the CHARGE consortium to test in C. elegans and novel mouse models.
Aim 2. Develop tools and resources to enable candidate gene testing and prioritization in C.elegans.
Aim 3. Develop novel mouse models of aging that allow further study of candidate genes in the Animal and Phenotyping Core.
| 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 |
| 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 |
| Lee, Benjamin P; Pilling, Luke C; Emond, Florence et al. (2016) Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans. Aging Cell 15:903-13 |
| 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 |
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