Endocrine News Podcast – Episode 91: Hypothyroidism and Muscle Regeneration
Host: Aaron Lohr (Endocrine Society)
Guest: Dr. Paola Aguiari, Senior Research Specialist, Children’s Hospital Los Angeles
Date: September 18, 2024
Overview
This episode dives into the crucial topic of how hypothyroidism impairs skeletal muscle regeneration after injury, focusing particularly on the role of muscle stem cells (satellite cells). Host Aaron Lohr interviews Dr. Paola Aguiari, who recently presented her research at ENDO 2024 on this very subject. The conversation covers the basics of muscle regeneration, the influence of thyroid hormone signaling, their experimental approach in mice, unexpected findings, and potential new therapeutic avenues.
Key Discussion Points & Insights
1. Thyroid Hormone and Muscle Regeneration
- Muscle Stem Cells ("Satellite Cells"):
- Muscle's regenerative capacity hinges on “satellite cells” – a type of tissue-resident stem cell dormant until activated by injury or exercise.
- Upon activation, these cells proliferate and differentiate to repair or replace muscle fibers.
- Quote:
“Skeletal muscle has a remarkable capability of regenerating thanks to the presence within the tissue of muscle stem cells... and they activate upon injury or after exercise and they enter a so called cell cycle.”
— Dr. Paola Aguiari [01:45]
- Role of Thyroid Hormone:
- Critical to both embryonic development and maintenance of postnatal muscle.
- Regulates fast/slow-twitch muscle fiber switching and contraction efficiency.
- Deficiency can lead to sarcopenia, weakness, pain, fatigue, and poor recovery from exercise.
- Both hypo- and hyperthyroidism are associated with muscle dysfunction.
2. Impact of Disrupted Thyroid Signaling
- Consequences of Hypothyroidism:
- Interferes with muscle homeostasis and adaptability.
- Inadequate regeneration post-injury or with aging.
- Quote:
“When thyroid hormone is not there, we cannot adapt our skeletal muscle mass... or we cannot regenerate after injury, or when we get old, we cannot compensate with new skeletal muscle as much as a person that has a euthyroid state.”
— Dr. Paola Aguiari [03:19]
3. Dr. Aguiari’s Research Study
Objective: Understand how hypothyroidism affects muscle regeneration post-injury.
-
Methodology:
- Induced hypothyroidism in mice via PTU and low-iodine diet.
- Inflicted muscle injury using cardiotoxin (from cobra venom).
- Tracked muscle regeneration in hypothyroid vs. euthyroid (normal thyroid) mice.
- Used single cell RNA sequencing, tissue histology, and a fluorescent reporter for tracing cell cycle progression in muscle stem cells.
- Monitored regeneration over two months.
-
Findings:
- Regeneration was impaired in hypothyroid mice, as expected.
- Unexpected Insight: Hypothyroidism didn’t just affect muscle cells – it also disrupted immune cells, vascular cells, and fibroadipogenic progenitors in the muscle tissue.
- Quote:
“What I wasn't expecting was that other population in the skeletal muscle were going to be impacted. So... immune cells, other population that are from vascular system or... fibroadiprogenic progenitors…”
— Dr. Paola Aguiari [06:41]
4. Therapeutic Implications and Future Directions
-
Restoring Thyroid Levels:
- Re-establishing normal thyroid hormone might restore regeneration, but not yet tested in the study.
-
Compensatory Pathways:
- Regeneration, though impaired, still occurs somewhat in hypothyroid mice.
- Suggests other molecular pathways compensate for deficient thyroid hormone.
- These could be explored for new drug targets.
- Quote:
“…some other molecular pathways, some other cells might intervene and compensate for the lack of thyroid… So these could be molecular targets for future drugs..."
— Dr. Paola Aguiari [07:54]
-
Continuing Research:
- Dr. Aguiari plans to investigate which molecular pathways and proteins are involved, aiming to identify actionable therapeutic targets.
Notable Quotes & Memorable Moments
-
On Why Muscle Stem Cells Are Fascinating:
“Skeleton muscle is one of the few tissue that actually have pure stem cells... the regeneration process... is a coordinated effort of different type of cells… since its physiology is very complicated, are a lot of things that can go wrong.”
— Dr. Paola Aguiari [04:19] -
On the Surprises in the Study:
“I wasn't expecting that hypothyroidism would impact also these other populations... it's up to us now [to] understand... the role of this old impacted population in the impaired regeneration in hypothyroidism.”
— Dr. Paola Aguiari [06:41] -
On the Importance of Molecular Pathways:
“If we cannot establish the correct level of thyroid hormone... these could be molecular targets for future drugs, future way to intervene…”
— Dr. Paola Aguiari [07:54] -
Enthusiasm for Further Research:
“We have some good insights of what these pathways may be, but we have it on the RNA level and... we need to explore more on the molecular level, on the protein level, and to confirm...”
— Dr. Paola Aguiari [09:01]
Timestamps for Key Segments
- 01:45 – Introduction to the role of thyroid hormone in muscle and muscle stem cell function
- 03:19 – Consequences of disrupted thyroid signaling (hypothyroidism)
- 04:19 – Dr. Aguiari’s motivation for focusing on muscle stem cells
- 05:15 – Explanation of study methodology and animal models
- 06:41 – Unexpected findings: Non-muscle cells also impacted by hypothyroidism
- 07:54 – Therapeutic considerations and future research directions
- 09:01 – Plans for further research into compensatory pathways
Conclusion
This episode offers an engaging and accessible overview of how thyroid hormone regulates muscle regeneration—and what goes awry in hypothyroidism. Dr. Aguiari’s research uncovers not only direct effects on muscle stem cells, but also the broader impact on various cell populations in muscle tissue, opening new avenues for therapeutic intervention. The conversation balances scientific precision with relevance for clinicians and researchers interested in endocrine health and muscle biology.