# Mitochondrial biogenesis, genetics and cell loss in mammalian aging

> **NIH NIH K02** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $160,164

## Abstract

PROJECT SUMMARY/ABSTRACT
Mitochondrial biogenesis is a target of many aging interventions. While the induction of mitochondrial
biogenesis is generally thought to be beneficial, our data indicate that activating mitochondrial biogenesis at
old age drives the intracellular accumulation of mitochondrial DNA (mtDNA) deletion mutations and results in
an 18% loss of muscle fibers and a 1,200% increase in electron transport chain (ETC) deficient muscle fiber
segments. These effects were antagonistically pleiotropic; they were not observed in treated young rats. Based
on our data, up-regulation of mitochondrial biogenesis in aged humans may cause significant skeletal muscle
damage. These studies will clarify the role of mitochondrial biogenesis in mtDNA deletion mutation
accumulation and evaluate the old-age specific effects of compounds that stimulate mitochondrial biogenesis
in skeletal muscle. This project will: define the antagonistic pleiotropy of mitochondrial biogenesis in muscle
fiber loss; test the hypothesis that mtDNA deletion genome accumulation drives fiber loss; specify the order of
events and time required between mitochondrial biogenesis, mtDNA deletion mutation accumulation and cell
death; refine proposed mechanisms for deletion accumulation; determine if geroprotectors, which target
mitochondrial biogenesis, antagonistically induce mtDNA deletion mutation accumulation. By understanding
the mechanisms of inducing mitochondrial biogenesis at old ages, we will specify targets and treatment
strategies that mitigate the antagonistic effects. This K02 award, if funded, will protect the candidate's research
time from overextended clinical and administrative duties to allow further research development.

## Key facts

- **NIH application ID:** 9939367
- **Project number:** 5K02AG059847-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jonathan Wanagat
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,164
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939367

## Citation

> US National Institutes of Health, RePORTER application 9939367, Mitochondrial biogenesis, genetics and cell loss in mammalian aging (5K02AG059847-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939367. Licensed CC0.

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