# Investigating the Impact of Telomere Specific Oxidative Base Damage in Cellular Aging

> **NIH NIH F32** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $40,206

## Abstract

Project Summary/Abstract
Telomeres play an essential role at the interface between cellular aging and carcinogenesis because they are
highly sensitive to oxidative stress. Oxidative stress, or the excess of free radicals, is a ubiquitous source of DNA
damage humans experience from normal metabolism, physical stress, exogenous sources such as pollution and
solar radiation, and by-products of immune cell signaling. While a link between telomere attrition and oxidative
stress exists, there have been no reports on how direct oxidative base damage to telomeric DNA impacts normal
cell biology. Our group has developed the first system to induce the common oxidative lesion 8-oxo-guanine
(8oxoG) specifically at telomeres by fusing a fluorogen activated peptide (FAP) to the telomere binding protein
TRF1. We have generated clonal cell lines that have homogenous FAP-TRF1 expression at the telomere, and
find that after a single induction of telomeric 8oxoG, normal cells exhibit a growth arrest, which we did not observe
in two cancer cell lines. The hypothesis of this fellowship is that telomeric 8oxoG is sufficient to produce a DDR
in normal cells that induces growth arrest, independent of telomere shortening, that depends on the p53/p21
signaling axis. Moreover, following induction of telomeric 8oxoG we observe an increase in the number of
micronuclei as early as one day after treatment. This project will also address how these micronuclei are forming,
if they are dependent on DNA replication, and if they are sensed by the cGAS/STING axis. Competition of this
project will delineate for the first time the contribution of telomeric oxidative stress to cellular outcomes
related to aging and cancer. This work will have general applications to all humans, but will also inform the
biology of age-related diseases that are associated with increased levels of oxidative stress, and may promote
health-span in either case.This fellowship also allows for the acquisition of new skills related to the aims of the
project, and has outlines specific mentors for each. This includes single molecule analyses of telomere
replication, live-cell imaging, RNA-sequencing, and detection of signaling molecules related to the immune
system. Moreover, career development is also a focus of this fellowship. It includes plans to attend workshops
related to experimental techniques and scientific writing, in addition to attending national and international
conferences to present the findings of this research project.

## Key facts

- **NIH application ID:** 10292913
- **Project number:** 5F32AG067710-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ryan P Barnes
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,206
- **Award type:** 5
- **Project period:** 2020-06-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292913

## Citation

> US National Institutes of Health, RePORTER application 10292913, Investigating the Impact of Telomere Specific Oxidative Base Damage in Cellular Aging (5F32AG067710-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10292913. Licensed CC0.

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