The Nathan Shock Center has created a strong environment in which to conduct research on aging through the provision of state-of-the-art research resources. The Center's Research Cores provide care for mouse colonies (Animal Core), phenotyping of these animals (Health Span Core), and tracking and analysis of the resulting data (Statistical Core). The overall goal of the Image Analysis Core is to develop and provide resources for the geroscience community to aid in computer-assisted histopathological analysis and discovery of age-related histological feature. Together these Cores foster shared use and collaborative research, and are utilized by researchers within and outside of the Center.
Currently in its 13thyear, the NIA-funded Shock Center is led by Ron Korstanje and Gary Churchill and consists of five cores, including an administrative core. The four research cores are:
The Animal and Phenotyping Core is continuing phenotyping of our large (800 mice) senolytics study in Diversity Outbred mice and has started tissue collection of the first waves of 24-month-old mice that are being used at the JAX-Sen Tissue Mapping Center. We continue to maintain colonies of C57BL/6J and Diversity Outbred (DO) mice for use in pilot project studies.
Our Development Core has successfully performed several pilot studies and is currently working on follow-up studies for some of them to get additional data or to go more in-depth on some aspects. For an overview of the pilot studies, click here.
The Data and Statistical Core is analyzing data from Calico DO and the Shock Center CC lifespan intervention studies. We are working with the Interventions Testing Program (ITP) Centers to examine historical data related to the reproducibility of aging studies, and we are wrapping up our work on end-of-life criteria in collaboration with Lab Animal Health.
The Image Analysis Core is developing machine-learning approaches to quantify age-related changes in different tissues that are matching pathologist scoring, which will allow us to measure the effects of genetics and interventions on these tissues during the aging process. The tools are now in place to perform analyses on kidney and liver, while heart and lung will soon follow. Furthermore, we developed a website with instructions and resources for investigators to use our approach in their own studies. For more information, click here.
The JAX-Sen Mouse Tissue Mapping Center is led by Nadia Rosenthal, Ron Korstanje, Paul Robson, and Ming Xu and is, like the KAPP-Sen Human Tissue Mapping Center in Farmington, a collaboration between JAX and UConn Health. The centers are part of the SenNet Consortium with the goal of generating atlases of senescent cells in different tissues. JAX-Sen is focusing on heart, kidney, pancreas, and placenta and uses different platforms (RNAseq, scRNAseq, Visium, CODEX, TimsTOF) to generate the data. Tissues are collected from C57BL/6J mice at different ages as well as a large cohort of aged 24-month-old Diversity Outbred mice that were aged and phenotyped by our Shock Center[MW1]. In addition to heart, kidney, and pancreas for our own Center, we are also collecting thymus, spleen, and lymph nodes for the Yale Tissue Mapping Center, and brain, liver, lungs, and muscle for the San Diego Tissue Mapping Center. Finally, we are generating two new mouse models in which fluorescent proteins are driven by the p16 and p21 promoters, which will allow easier detection of senescent cells.
The ITP tests if interventions in adult mice extend median and maximal lifespans, and delay of age-sensitive changes in several biological systems relevant to health. Successful interventions are tested at different doses and starting ages, and in more biological systems. Tissues and mice are provided to collaborators, and The Mouse Phenome Database curates ITP data.
This program has been funded by the NIA since 2004 and studies are performed at three sites (University of Texas, San Antonio, University of Michigan, and JAX). The JAX site has been under the leadership of David Harrison since 2004, David Harrison and Nadia Rosenthal since 2019, and Ron Korstanje was added as deputy director in 2022. With the platforms and pipelines that are being developed in our JAX-Sen Tissue Mapping Center and the geropathology tools that we developed in our Shock Center, we are in a perfect position to increase the focus on gene expression and histopathology to further advance the ITP studies.