# Comparative Genomics of Longevity

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2022 · $2,202,181

## Abstract

SUMMARY: The overarching goal of this Program Project Grant (PPG), entitled “Comparative Genomics of
Longevity,” is to identify molecular mechanisms responsible for health and longevity, with the focus on
genome/epigenome stability in long-lived rodent species, and then develop strategies to adapt these
mechanisms to benefit human health. Rodents are an ideal group for comparative aging studies because they
are phylogenetically related, even though their lifespans are extremely diverse, ranging from 2-4 years in mice
and rats to over 20 years in naked mole rats, beavers, porcupines, and squirrels. Characterization of the
processes responsible for this disparity in lifespan may enable the development of interventions in the aging
process to prevent, delay or cure age-related diseases. The central hypothesis of this PPG, therefore, is that
long-lived species have evolved more efficient mechanisms to maintain genome/epigenome stability and
prevent age-related diseases, which can be adapted to extend the healthspan of other species. In the first
phase of the PPG, we generated exciting data that support our central hypothesis. Specifically, we identified
DNA double strand break repair as a mechanism that strongly correlates with longevity; we were able to improve
DNA repair in mouse cells by introducing specific amino acid changes from the beaver; we showed that the
naked mole rat hyaluronan synthase 2 gene improved mouse health; we obtained evidence that mutation rates
are higher in short-lived species, we developed a model that reports the biological age of mice, and we identified
multiple omics profiles characteristic of long-lived species. This PPG is comprised of four highly integrated
projects and three cores. Project 1 (Vera Gorbunova) is focused on mechanisms responsible for more efficient
genome/epigenome stability in long-lived species. Project 2 (Andrei Seluanov) studies mechanisms responsible
for longevity and cancer-resistance of the longest-lived rodent, the naked mole rat. Project 3 (Jan Vijg)
investigates whether long-lived species have lower frequencies of mutations and epimutations using novel, high
throughput single-cell approaches. Project 4 (Vadim Gladyshev) uses omics approaches to identify genes and
pathways involved in genome and epigenome stability that are differentially regulated in long-lived species. The
research team consists of five investigators dedicated to longevity research who are experts in comparative
biology and DNA repair (Gorbunova), cancer-resistance and long-lived rodents (Seluanov), mutagenesis and
high throughput, single-cell approaches (Vijg), comparative genomics (Gladyshev), and bioinformatics (Zhang,
Core C). Moreover, the team has developed a collection of primary rodent cells and tissues, and naked mole rat
colonies, specifically to facilitate comparative studies of longevity (Seluanov, Core B). This assembly of expertise
allows unprecedented insight into the biology of longevity. This team of investi...

## Key facts

- **NIH application ID:** 10399516
- **Project number:** 5P01AG047200-09
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Vera Gorbunova
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,202,181
- **Award type:** 5
- **Project period:** 2014-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399516

## Citation

> US National Institutes of Health, RePORTER application 10399516, Comparative Genomics of Longevity (5P01AG047200-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399516. Licensed CC0.

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