# Genome and epigenome stability in long- and short-lived animal species

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2024 · $677,073

## Abstract

Summary: The central hypothesis of Project 3 is that the rate of stochastic damage at genome and epigenome
level is a major factor in the control of species-specific life span. Both DNA mutations and epimutations figure
prominently as drivers of aging clocks, i.e., biomarkers of aging, and have been implicated as causal factors in
aging and age-related diseases, including Alzheimer's Disease and Related Dementias. Project 3 is studying the
rate of stochastic alterations in genome, epigenome, and transcriptome. Recent advances in omics technology,
including our own development of new, single-cell and single-molecule methods, allow the accurate quantitative
detection of de novo somatic mutations in normal cells and tissues, including genome structural variants. In the
previous, still ongoing project period we used one of these methods to show that somatic mutation rate inversely
correlates with species-specific lifespan. We also showed that rate and persistence of mutagen-induced,
stochastic changes in the DNA methylome and transcriptome are higher in cells from short-lived as compared
to long-lived rodents. Using these methods, as well as recently emerged long-read sequencing methods we will
now specifically test the hypothesis that genome structural variation (Aim 1) and DNA methylation changes (Aim
2), induced by g-radiation in primary cells from up to 50 species with great differences in lifespan, are more
severe and occur at a higher rate in short- as compared to long-lived species. We will also test specific
interventions to increase genome maintenance developed in Project 1 for an effect on the maintenance of
genome sequence integrity, new rodent models for Azheimer’s Disease developed in Project 2 for increased
somatic mutation rate in brain, and develop new, genome or epigenome-based molecular clocks with Project 4.

## Key facts

- **NIH application ID:** 10848568
- **Project number:** 2P01AG047200-11
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JAN VIJG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $677,073
- **Award type:** 2
- **Project period:** 2014-05-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848568

## Citation

> US National Institutes of Health, RePORTER application 10848568, Genome and epigenome stability in long- and short-lived animal species (2P01AG047200-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10848568. Licensed CC0.

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