Human genetic variation plays a significant role in regulating differences in longevity and changes in overall health and disease susceptibility with age. Understanding the links between genetic variation and the biology of aging promises to ultimately identify approaches to extend the human healthspan. However, healthspan is a complex trait, and determining the interacting polymorphic alleles and environmental factors that affect it is difficult. Meeting this challenge will require a systems approach to aging, utilizing an experimental organism that models the genetic and biological complexity of the human population. The Jackson Shock Center (JSC) proposes to use its expertise in mouse models and complex traits to build on successes of the previous funding period and to develop the unique resources necessary to enable the aging community to elucidate the genetic underpinnings of healthspan. Specifically, JSC will provide: ^) Aging Mice &Tissues through a central core of large crosses and reference populations, including the Collaborative Cross lines, which offer unprecedented genetic variation;2) Mouse populations genotyped and comprehensively characterized for physiological and behavioral traits relevant to aging and healthspan; 3) Novel Statistical Methods developed to enable researchers to identify correlations, narrow QTL, and to understand causal versus reactive relationships of aging related traits;and 4) Integrated Mouse and Human Aging Data assembled into an annotated genetic map of mouse and human aging loci to enable researchers to rapidly identify and validate genes implicated in human aging and to suggest translational interventions to extend healthspan. All JSC resources, methods, phenotypic and genetic data, and maps will be publically available through the Mouse Phenome Database (MPD), the JSC website, and a proposed web portal, which will integrate the resources and information of the Nathan Shock Centers (NSC). JSC will provide unprecedented, coordinated aging resources and a vibrant intellectual environment to support 29 faculty and more than 20 independent, grant-funded research projects aimed at unraveling genetic control of human aging at The Jackson Laboratory (JAX). These resources will be broadly disseminated to support more than 20 existing collaborations as well as numerous external aging investigators, greatly expanding JSC's role as a center for national aging research. In the long term, JSC will continue to focus JAX expertise in genomics and biology on aging, leading to enhanced resources forth research community and a better understanding of the molecular mechanisms of lifespan and healthspan.
Human aging is influenced by genetic factors. Differences in longevity as well as changes in health and disease-risk with time are linked with variation in individuals'genetic codes. The Jackson Shock Center will develop resources to identify genetic differences and probe their role in controlling healthy aging. Resources will include: aged mouse models, mirroring human genetic variation;physiological and behavioral data for age-related traits;and methods to reveal genetic factors tied to human aging. Resources will be available to the scientific community, accelerating research to understand and ultimately prolong healthy human aging.
|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|
|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|
|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|
|Ackert-Bicknell, Cheryl L; Anderson, Laura C; Sheehan, Susan et al. (2015) Aging Research Using Mouse Models. Curr Protoc Mouse Biol 5:95-133|
|Yuan, Rong; Gatti, Daniel M; Krier, Rebecca et al. (2015) Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating IGF1. J Gerontol A Biol Sci Med Sci 70:817-26|
|Bogue, Molly A; Churchill, Gary A; Chesler, Elissa J (2015) Collaborative Cross and Diversity Outbred data resources in the Mouse Phenome Database. Mamm Genome 26:511-20|
|Aziz, Moammir H; Chen, Xundi; Zhang, Qi et al. (2015) Suppressing NRIP1 inhibits growth of breast cancer cells in vitro and in vivo. Oncotarget 6:39714-24|
|Reznichenko, Anna; Korstanje, Ron (2015) The role of platelet-activating factor in mesangial pathophysiology. Am J Pathol 185:888-96|
|Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry et al. (2015) A roadmap for the genetic analysis of renal aging. Aging Cell 14:725-33|
|Yu, Weiqun; Ackert-Bicknell, Cheryl; Larigakis, John D et al. (2014) Spontaneous voiding by mice reveals strain-specific lower urinary tract function to be a quantitative genetic trait. Am J Physiol Renal Physiol 306:F1296-307|
Showing the most recent 10 out of 39 publications