# DNA Repair, Mutations and Cellular Aging

> **NIH NIH P01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $2,015,865

## Abstract

ABSTRACT – Overall
Progress in aging research over the last two decades has now firmly established an important role for DNA
damage and genome instability in age-related cellular degeneration and death. Since its inception in 1999
investigators in this PPG demonstrated that genetic defects in some but not all DNA repair pathways are
associated with premature aging phenotypes in mice, developed the first methods to detect spontaneous DNA
mutations in primary tissues, identified transcription stress as a novel age-related molecular phenotype,
developed a mouse model to detect and eliminate senescent cells in mice and subsequently demonstrated
causality in aging phenotypes, and provided the first evidence that rare genetic variants in genome
maintenance pathways are enriched in human centenarians. Studies from other groups have confirmed many
of our conclusions, and genome instability is now regarded a hallmark of aging. However, what remains lacking
is specific insight into the genetic control and molecular mechanisms that link DNA damage and genome
instability to aging and longevity in humans. This renewal application is organized around three major
research questions that remain in this field: (1) the key genome maintenance genotypes that control human
aging and longevity; (2) the genetic and molecular basis of DNA damage-driven aging; and (3) How DNA
damage and its molecular sequelae affect cell fate diversity in aging. These key questions will be addressed
jointly and in an integrated manner by four research projects, an Administrative Core and a Bioinformatics
Core. We expect that the resulting specific insight into the role of DNA damage and repair in human aging will
give us the means to develop interventions to minimize the adverse effects of DNA damage metabolism.

## Key facts

- **NIH application ID:** 9964604
- **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:** $2,015,865
- **Award type:** 5
- **Project period:** 1999-04-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964604

## Citation

> US National Institutes of Health, RePORTER application 9964604, DNA Repair, Mutations and Cellular Aging (5P01AG017242-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964604. Licensed CC0.

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