# The effects of exercise on satellite cell dynamics during aging

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $274,322

## Abstract

Abstract
A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and
strength. Although the etiology of sarcopenia remains to be determined, studies in humans and rodents have
reported a strong correlation between the loss and/or dysfunction of satellite cells and sarcopenia. Despite the
correlation between declining satellite cell-dependent regenerative capacity and age, no studies to date have
directly tested this relationship to determine if the loss of satellite cells causes sarcopenia. To test this idea, we
depleted (>85%) satellite cells in five month old mice to a level dramatically lower than that observed with
normal aging. A detailed analysis of multiple muscles through 24 months of age revealed that, despite
significantly reduced regenerative capacity, the life-long depletion of satellite cells did not accelerate nor
exacerbate sarcopenia; however, the depletion of satellite cells at a young age was associated with a
significant increase in fibrosis in old mice. These highly provocative findings, together with our data on the
fiber-type specific role of satellite cells in response to exercise, reveal our limited understanding of how aging
affects the function of satellite cells in skeletal muscle maintenance, the development of fibrosis and in
response to a growth stimulus; addressing these fundamental gaps in our knowledge clearly requires new
tools. Towards this end, we will utilize a novel mouse strain (Pax7-H2B-GFP) that will allow us to track satellite
cell dynamics for the first time in adult skeletal muscle aging. To better understand how aging and exercise
affects satellite cell dynamics and the regulation of fibrosis, the following aims will be pursued: 1) determine
how age and life-long exercise affects satellite cell dynamics in the maintenance of skeletal muscle, 2)
determine how age and life-long exercise affects satellite cell regulation of fibrosis and 3) determine how age
affects satellite cell dynamics in response to a growth stimulus. The approaches described herein use
powerful, new genetic tools to determine how aging and life-long exercise alters the function of satellite cells in
skeletal muscle homeostasis, regulation of fibrosis and adaptability. The development of the Pax7-H2B-GFP
mouse represents a long sought-after method for tracking satellite cells, especially following fusion into the
myofiber. This novel mouse strain will allow us to address formally intractable questions regarding how satellite
cell dynamics are affected by age and life-long exercise. Such fundamental knowledge is necessary to critically
evaluate the therapeutic value of satellite cells for the treatment of muscle mass loss and function associated
with aging.

## Key facts

- **NIH application ID:** 9822147
- **Project number:** 5R01AG049806-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** JOHN Joseph MCCARTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $274,322
- **Award type:** 5
- **Project period:** 2016-01-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822147

## Citation

> US National Institutes of Health, RePORTER application 9822147, The effects of exercise on satellite cell dynamics during aging (5R01AG049806-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822147. Licensed CC0.

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