Inspired by Matt Laye’s excellent blog on sarcopenia, the loss of muscle mass during aging, I’ve decided to write a follow up blog about unusual cases that have taught scientists about the mechanisms behind muscle loss and how to prevent it. This is not the first article written on the subject, so please read more here, here and here.
Our story begins with a breed of cows that was identified in Belgium in 1808. These cows displayed an unusually muscular appearance, and in the years since, have been used for both dairy and meat. It was discovered that this condition is caused by an inherited recessive mutation that “breaks” an important signaling molecule known as myostatin. The same year the gene was identified in cows, another research group generated a similar genetic mutation in mice to demonstrate that the loss of function of myostatin is enough to cause muscle cell growth (hypertrophy) and increased muscle fiber number (hyperplasia). In the years since its discovery, mutations in myostatin have been identified in dogs and even in humans.
So how does myostatin work? Well, it appears that the gene is a negative regulator of muscle growth and tells muscles when to stop growing. So without myostatin, the “normal” balance is shifted and individuals with the mutation (regardless of whether they are mice, dogs, humans, or cows) end up with far more muscle than is normal.
Given the issues associated with sarcopenia as people age, is altering myostatin expression a viable option to help people live better lives? In short, the answer is yes. As Matt’s piece stated, exercise and physical activity are great ways to counter sarcopenia during aging. Interestingly, it turns out that these effects seem to partially happen through alteration of myostatin protein levels. We here at SAGE wholeheartedly endorse exercise as an effective way for individuals to improve healthspan (but please talk to your doctor for specific advice about types/duration and to confirm that you’re healthy enough to do so). Despite the benefits of exercise, there are people and disease conditions that cannot be fully treated by exercise, for example, cancer patients or people with muscular dystrophies. For these people, drugs to block myostatin or to mimic the beneficial effects of exercise have been proposed as effective methods to rebuild damaged or atrophied muscle. Multiple drug companies are working on such approaches, but no therapeutics have made it to the market yet.
Of course, it’s not just cancer patients and the elderly who would like to take a pill that boosts muscle growth. Athletes and bodybuilders have been clamoring for such an inhibitor (legal or illegal), and plenty of snake-oil salespeople have been willing to oblige. Needless to say we here at SAGE cannot object to these unproven, poorly regulated supplements strongly enough. Do not buy them. Do not take them.
So to bring this back around to aging, myostatin inhibition may be an effective pharmacological intervention to reduce the effects of sarcopenia. Additionally, myostatin may not be alone: a very closely related protein, GDF11 (myostatin is also known as GDF8) declines during aging, and is one factor that seems to be involved in the anti-aging effects seen in parabiosis experiments previously described in an excellent blog post from Brandon Tavshanjian. This points to systemic factors being at least partially responsible for and capable of altering some aspects of aging. It would not be surprising to see more anti-aging factors identified and exploited to help treat diseases of aging and extend healthspan in the future.