Today I’m going to use our former governor Arnold Schwarzenegger as an example of what happens to our muscles when we age.
One of Arnold’s many talents when he was younger was being a professional bodybuilder. As you can see in this photo, Arnold worked hard to generate an impressive amount of muscle that landed him lead roles in movies Conan the Barbarian and The Terminator.
If you look at pictures of Arnold now (who is now 68), while still being an impressively large human being, it’s obvious that much of his muscular bulk has diminished. That’s because as humans age, so do their muscles.
Muscles shrink with age
As muscles age, they slowly lose mass and shrink (a condition called sarcopenia) because of a number of reasons – one of them being their inability to regenerate new muscle tissue efficiently. The adult stem cells responsible for muscle regeneration are called satellite cells. When muscles are injured, satellite cells are activated to divide and generate new muscle fibers that can repair injury and also improve muscle function.
However, satellite cells become less efficient at doing their job over time because of environmental and internal reasons, and scientists are looking for new targets that can restore and promote the regenerative abilities of muscle stem cells for human therapeutic applications.
A study published earlier this week in Nature Medicine, identified a potential new target that could boost muscle stem cell regeneration and improved muscle function in a mouse model of Duchenne muscular dystrophy.
β1-integrin is important for muscle regeneration
Scientists from the Carnegie Institute of Washington found that β1-integrin is important for maintaining the homeostasis (or balance) of the muscle stem cell environment. If β1-integrin is doing its job properly, muscle stem cells are able to go about their regular routine of being dormant, activating in response to injury, dividing to create new muscle tissue, and then going back to sleep.
When the scientists studied the function of β1-integrin in the muscles of aged mice, they found that the integrin wasn’t functioning properly. Without β1-integrin, mouse satellite cells spontaneously turned into muscle tissue and were unable to maintain their regenerative capacity following muscle injury.
Upon further inspection, they found that β1-integrin interacts with a growth factor called fibroblast growth factor 2 (Fgf2) and this relationship was essential for promoting muscle regeneration following injury. When β1-integrin function deteriorates as in the muscles of aged mice, the mice lose sensitivity to the regenerative capacity of Fgf2.
Restoring muscle function in mice with muscular dystrophy
By using an antibody to artificially activate β1-integrin function in the muscles of aged mice, they were able to restore Fgf2 responsiveness and boosted muscle regeneration after injury. When a similar technique was used in mice with Duchenne muscular dystrophy, they observed muscle regeneration and improved muscle function.
The authors believe that β1-integrin acts as a sensor of the muscle stem cell environment that it maintains a balance between a dormant and a regenerative stem cell state. They conclude in their publication:
“β1-integrin senses the SC [satellite cell] niche to maintain responsiveness to Fgf2, and this integrin represents a potential therapeutic target for pathological conditions of the muscle in which the stem cell niche is compromised.”
Co-author on the study Dr. Chen-Ming Fan also spoke to the clinical relevance of their findings in a piece by GenBio:
“Inefficient muscular healing in the elderly is a significant clinical problem and therapeutic approaches are much needed, especially given the aging population. Finding a way to target muscle stem cells could greatly improve muscle renewal in older individuals.”
Does this mean anyone can be a body builder?
So does this study mean that one day we can prevent muscle loss in the elderly and all be body builders like Arnold? I highly doubt that. It’s important to remember these are preclinical studies done in mouse models and much work needs to be done to test whether β1-integrin is an appropriate therapeutic target in humans.
However, I do think this study sheds new light on the inner workings of the muscle stem cell environment. Finding out more clues about how to promote the health and regenerative function of this environment will bring the field closer to generating new treatments for patients suffering from muscle wasting diseases like muscular dystrophy.