# Mechanisms and functional impact of genome instability in aging

> **NIH NIH P01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $405,891

## Abstract

ABSTRACT – Project 2
Genome instability refers to the tendency of the genome to undergo a range of irreversible DNA mutations,
from base substitutions to chromosomal alterations. In contrast to DNA damage, DNA mutations cannot be
repaired and have been implicated as a cause of aging since the 1950s. However, it has proved very difficult to
test whether genome instability underlies, at least in part, the gradual loss of function and increased
degenerative disease risk associated with aging. This is because somatic mutations are difficult to detect in
normal, non-clonal tissues. New, single-cell whole genome sequencing technology, developed by Project 2 as
part of this PPG, makes it possible to study different types of somatic mutations and their distribution across
the genome directly in human or mouse tissues. In Aim 1, Project 2 will first test the effects on genome
instability of rare genome maintenance genotypes associated by Project 4 with accelerated or delayed aging in
humans. Then, with Project 1, we will test the possible functional impact of genome instability on human aging
(Aim 2). Finally, with Project 3 we will test the possible role of genome instability in cellular senescence (Aim
3).
The results of Project 2 should, for the first time, provide insight into genome instability in human primary cells
as a function of age and its possible causal contribution to aging.

## Key facts

- **NIH application ID:** 9964616
- **Project number:** 5P01AG017242-25
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JAN VIJG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,891
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964616

## Citation

> US National Institutes of Health, RePORTER application 9964616, Mechanisms and functional impact of genome instability in aging (5P01AG017242-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964616. Licensed CC0.

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