# Determination of circulation factors that mediate the health benefits of exercise in mitochondrial aging

> **NIH NIH R41** · CYTEGEN CORPORATION · 2020 · $252,092

## Abstract

Project Summary/Abstract:
This proposal seeks to test the hypothesis that endurance exercise stimulates the release of circulating factors
that improve mitochondrial fitness. CyteGen’s goal is to identify these endogenous factors and engineer them
to treat diseases in which mitochondrial dysfunction is central. These diseases include neurodegenerative
and other diseases associated with aging, as well as the rare mitochondrial diseases that arise from inborn
errors in genes encoding mitochondrial proteins that affect 1 in 5000 individuals. Currently, no effective
treatments are available. To identify factors that improve mitochondrial fitness, CyteGen is using a unique
mouse model, created by the PI. This model displays a profound mitochondrial syndrome with reduced life
span and premature aging due to impaired exonuclease proofreading activity of POLG, the sole mtDNA
polymerase. POLG is highly conserved between mice and humans and over 200 mutations in this polymerase
have been associated with human disease, supporting CyteGen’s contention that mouse discoveries will
translate into humans. Endurance exercise of POLG mutant mice reverses the early-onset aging syndrome
by overcoming the POLG defect in mitochondrial function. Analyses of tissues in exercised mice suggests
that endogenous circulating factors may be responsible. We will test the hypothesis that circulating factors
secreted as a result of exercise improve mitochondrial function by collecting plasma from exercised POLG
mice and sedentary controls and injecting it into old POLG mice that display reduced mitochondrial function
and impaired skeletal muscle and cardiac function. Following a schedule of injections that mimics exercise
training, we will examine metabolic capacity, cardiac function, spontaneous activity levels and mitochondrial
function. A second aim of this study is to use cell based models to determine the effects of plasma from
exercised mice on mitochondrial function of POLG mutant cells. The goal of our studies is to identify circulating
factors that reverse mitochondrial dysfunction with suitable properties to support initiation of preclinical studies
in preparation for clinical evaluation.

## Key facts

- **NIH application ID:** 10011425
- **Project number:** 1R41AG065131-01A1
- **Recipient organization:** CYTEGEN CORPORATION
- **Principal Investigator:** TOMAS ALBERTO PROLLA
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,092
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011425

## Citation

> US National Institutes of Health, RePORTER application 10011425, Determination of circulation factors that mediate the health benefits of exercise in mitochondrial aging (1R41AG065131-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011425. Licensed CC0.

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