# Mitochondrial biogenesis, genetics and cell loss in mammalian aging

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $394,211

## 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.
Project outcomes:
· Specify the cellular pathways and ages at which inducing mitochondrial biogenesis increases mtDNA
 deletion mutation frequency, ETC deficiencies and fiber loss.
· Infer the causality of mitochondrial biogenesis in fiber loss by specifying the order of events and time
 required between mitochondrial biogenesis, mtDNA deletion mutation accumulation and cell death.
· Determine whether other AMPK or peroxisome proliferator-activated receptor agonists, which target
 mitochondrial biogenesis, also induce deletion mutation accumulation and cell death when initiated at old
ages.
· Downregulate mitochondrial biogenesis in old rats to prevent ETC deficiencies and fiber loss.
By understanding the mechanisms and impacts of inducing mitochondrial biogenesis at old ages, we will
specify targets and treatment strategies that mitigate the antagonistic effects.

## Key facts

- **NIH application ID:** 10443536
- **Project number:** 5R01AG055518-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** JUDD M. AIKEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,211
- **Award type:** 5
- **Project period:** 2017-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443536

## Citation

> US National Institutes of Health, RePORTER application 10443536, Mitochondrial biogenesis, genetics and cell loss in mammalian aging (5R01AG055518-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10443536. Licensed CC0.

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