Models of Genome Instability Core

Core Overview

The Models of Genome Instability and Aging core is dedicated to investigating how DNA damage—particularly spontaneous, endogenous damage—drives aging and age-related diseases. Recognizing genome instability as a primary hallmark of aging, this core focuses on understanding the impact of both endogenous genotoxic stress (e.g., oxidative and hydrolytic damage) and exogenous insults. It provides a critical platform for studying the consequences of chronic DNA damage response (DDR) activation, which can lead to cell senescence, apoptosis, and systemic inflammation, ultimately compromising tissue function and stem cell viability. By supplying access to rare and highly specialized human and murine models with well-characterized DNA repair deficiencies, this core enables researchers to study how genome instability intersects with other hallmarks of aging, such as mitochondrial dysfunction, epigenetic changes, and immune dysregulation.

This core achieves its mission through three main aims: (1) offering primary and immortalized cells from human subjects with known genome instability disorders affecting key DNA repair pathways; (2) providing access to a wide array of tissues, primary cells, and live mice with defects in genome maintenance or age-associated DNA damage; and (3) generating new murine and human models to interrogate the downstream effects of genome instability on other aging processes. This core houses an extensive biorepository of over 100,000 tissue samples and employs sophisticated data systems to facilitate resource sharing. In sum, this core empowers the geroscience community with unparalleled tools to explore the mechanistic links between DNA damage and the broader aging phenotype.