# Cellular Basis for Radiation induced acceleration of sarcopenia in juvenile cancer survivors

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $116,818

## Abstract

ABSTRACT:
 Although estimates indicate the 5-year survival rate of children diagnosed with a malignancy is near
80%, the vast majority of these individuals prior to the age of 40 demonstrate indices of physical limitation
normally associated with the elderly population. Among the age-related phenotypes observed earlier in
childhood cancer survivors is sarcopenia, the accelerated loss of lean body skeletal muscle tissue and strength
with age. Sarcopenia is characterized by loss of muscle stem cells (satellite cells) and chronic low-grade
inflammation, which causes atrophy of muscle fibers (myofibers). This proposal is designed to elucidate if
juvenile radiation treatments lead to systemic loss of satellite cells that 1) impairs juvenile skeletal muscle
maturation, and 2) accelerates sarcopenia in childhood cancer survivors. Importantly, we propose that satellite
cell-specific forced expression of sprouty1 (Spry1), a receptor tyrosine kinase feedback regulator, can prevent
systemic loss of satellite cells, skeletal muscle declines, and low-grade inflammation induced by juvenile
irradiation. To accomplish these objectives satellite cell-specific mouse genetic models, interrogation of
skeletal muscle morphology, physiology, and inflammation in response to juvenile irradiation will be conducted.
We have generated preliminary data that show satellite cell activity and contribution persists after P21
(weaning age in mice) and declines ~P42 (puberty onset), suggesting that radiation could damage muscle
growth up to puberty. Indeed, depletion of satellite cells, or local irradiation at juvenile stages (P28) induced
loss of myonuclei and atrophy. Furthermore, the irradiation leads to persistent satellite cell loss and elevated
macrophage content, a source of atrophy inducing cytokines. Consistent with a systemic effect, irradiation of
one leg triggered atrophy, loss of myonuclei and satellite cells, and increased macrophage content in
contralateral muscles. In addition, in satellite cells from irradiated muscle we find reduced expression of Spry1.
We will solidify our preliminary findings, and assess the consequences of satellite cell depletion and irradiation
on juvenile skeletal muscle maturation and sarcopenia. In addition, we will examine if satellite cell specific
Spry1 forced expression can prevent juvenile radiation induced acceleration of sarcopenia. The specific aims
of this proposal are: 1) To determine if satellite cell depletion at juvenile stages leads to sustained muscle
decline, and low-grade inflammation, 2) To determine if juvenile radiotherapy induces systemic and persistent
satellite cell loss, muscle decline, and low-grade inflammation, and 3) To determine if satellite cell-specific
forced Spry1 expression prevents juvenile radiotherapy-mediated systemic loss of satellite cells, muscle
decline, and low-grade inflammation. Data from this proposal should rigorously define the role of satellite cells
in juvenile radiotherapy-induced sarcop...

## Key facts

- **NIH application ID:** 10219985
- **Project number:** 5R01CA220467-05
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Joe Chakkalakal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $116,818
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219985

## Citation

> US National Institutes of Health, RePORTER application 10219985, Cellular Basis for Radiation induced acceleration of sarcopenia in juvenile cancer survivors (5R01CA220467-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219985. Licensed CC0.

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