# Role of Thyroid Hormone Signaling in Sarcopenia

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2020 · —

## Abstract

Sarcopenia is an age-related syndrome characterized by a decrease in muscle mass and associated with a loss
of strength and power, diminished functional performance, and increased disability and mortality. It is associated
with several pathological condition including chronic disease and myopathy. The prevalence of sarcopenia is
approximately 25% of the U.S. population over 70 years of age, thus greatly increased government healthcare
expenditures by an expanding elderly population. This could be even more burden for the VA healthcare because
the Veteran population is older than the general population. One of the mechanism involved in skeletal muscle
sarcopenia is loss or senescence of stem cells resident in the skeletal muscle. Satellite cells are stem cells
located beneath the basal lamina in close contact with the muscle fiber and are the major players in postnatal
muscle growth and regeneration after injury. Thyroid hormones act as pleiotropic factors in various tissues during
development by regulating genes involved in growth and differentiation, including skeletal muscle. We recently
showed that thyroid hormone receptor α (TRα) plays a crucial role in satellite cell proliferation and differentiation
and skeletal muscle regeneration after injury. In this proposal we hypothesize that TRα, modulating skeletal
muscle satellite cell senescence, is a key regulator in maintaining skeletal muscle mass during aging. Our
preliminary observations demonstrate that a mice carrying a Resistance to Thyroid Hormone (RTH)-associate
mutation for TRα has reduced muscle mass and strength and capability to regenerate after injury with aging.
We are planning several studies devoted to extend our knowledge on molecular basis of thyroid hormones and
TRα regulation of muscle stem cell senescence with aging. We will evaluate whether satellite-cell-intrinsic
alterations may cause the loss in muscle and regenerative decline with age in mice with TRα mutations with a
serial of in vivo transplantation strategies. We will analyze gene and protein expressions associated with
transcription factors for quiescence, self-renewal, proliferation and differentiation of satellite cell and associated
with chromatin remodeling by chromatin immunoprecipitation (ChIP)
in vitro and in vivo animal model.
Our goal
is to identify therapeutic targets with the potential to promote satellite cell proliferation, differentiation, and
response to injury, in conditions such as sarcopenia and skeletal muscle loss.

## Key facts

- **NIH application ID:** 9933793
- **Project number:** 5I01BX003665-04
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Anna Milanesi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933793

## Citation

> US National Institutes of Health, RePORTER application 9933793, Role of Thyroid Hormone Signaling in Sarcopenia (5I01BX003665-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933793. Licensed CC0.

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