# Mitochondrial DNA Deletion Mutation Frequency as a Metric of Biologic Age

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $416,911

## Abstract

PROJECT SUMMARY/ABSTRACT
Due to advances in geroscience, aging must be considered a modifiable risk factor for the major causes of
death. Interventions targeting human aging are ongoing, but there is a lack of predictive biomarkers to
measure the effectiveness of these interventions. With age, somatically-derived mitochondrial DNA (mtDNA)
deletions clonally accumulate within individual cells across a variety of tissues. Attaining high intracellular
abundance, mtDNA deletions disrupt oxidative phosphorylation, cellular function, and result in cell death. We
hypothesize that human mtDNA deletion frequency predicts the risk of morbidity and mortality and responds to
interventions that alter healthspan.
We have developed a digital PCR assay that quantifies mtDNA deletion frequency using total DNA samples
from any tissue in rodents and humans. This assay provides absolute quantitation, is amenable to a 96-well
format, correlates strongly with the subsequent cellular phenotypes including cell death, and has a detection
limit below one part per million. MtDNA deletion mutation frequency increases exponentially with age and this
increase parallels the age-induced accumulation of dysfunctional cells, tissue degeneration, and mortality. This
project will further develop and validate mtDNA deletion frequency as a measure of cell death in human aging.
We are validating the test in accordance with FDA guidelines for bioanalytical assays. We are measuring
mtDNA deletion frequency in a number of human tissues and biofluids across the human lifespan and will
establish the relationship between mtDNA deletion frequency, chronological age, clinical and physiological
outcomes, and interventions targeting human aging.

## Key facts

- **NIH application ID:** 10617844
- **Project number:** 5R01AG069924-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jonathan Wanagat
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $416,911
- **Award type:** 5
- **Project period:** 2022-05-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617844

## Citation

> US National Institutes of Health, RePORTER application 10617844, Mitochondrial DNA Deletion Mutation Frequency as a Metric of Biologic Age (5R01AG069924-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10617844. Licensed CC0.

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