Could Blocking This Protein Protect Aging Muscles?

Muscle growth and loss are kept in careful balance during youth, but could blocking a growth inhibitor called myostatin prevent age-related muscle atrophy? 

Why do we have myostatin and what is it?

You can see the uninhibited muscle growth in dogs with mutated myostatin on the right.

Myostatin is a myogenesis inhibitor, which means it stops stem cells differentiating into muscle cells. The signal strength is dependent on its concentration, and muscle growth and loss is usually kept in careful balance to maintain a balance between resources and strength. After all, if you're starving muscles are a ripe source of energy to survive - but you also need them to catch prey. Muscle drops off as we get older, but it's not certain whether this is a response to damage like dwindling numbers of good quality stem cells.

It's a common doping target

A German boy born with a rare mutation affecting myostatin could lift 3kg at the age of 4. This shows how effective even a modest lowering of the protein can be on muscle formation. Many companies are currently researching ways of inhibiting expression and blocking its activity to treat devastating diseases like muscular dystrophy. Popular supplement creatine might also have protective effects.

New candidate drugs

A startup called Scholar Rock has now unveiled data on a compound called SRK-015 - which inhibits a precursor to myostatin. Without this precursor, the protein fails to form and mature properly. Novartis is also working on an antibody called bimagrumab, in the hopes of treating common muscle-wasting conditions like age-related sarcopenia. Another experimental approach could be gene therapy; Bioviva has developed a gene therapy treatment for delivery of a myostatin inhibitor which looks promising so far.

Are there side effects?

One initial concern was that while myostatin inhibits growth, it might also conserve stores of satellite cells that replenish muscle. It was feared massive growth could cause later health problems by depleting the store of replenishing cells. This hasn't been found to be the case so far, and it looks like myostatin prevents wasting more than increasing satellite cell proliferation. It may be certain therapies could actually have wider benefits too; the inhibitor follistatin also has anti-inflammatory benefits. 

Skeletal muscle loss in sarcopenia during aging, which causes frailty and reduces quality of life

There is however some data suggesting the muscle growth can cause brittle tendons, which makes muscle injury more likely. Another concern is heart health, as one study found that higher levels of myostatin and a similar protein called GDF11 were associated with a lower risk of death or heart disease. Could lowering this protein further therefore be a bad thing? There are many red herrings in the aging process and it's difficult to differentiate response from cause. Do myostatin inhibitors reverse some aspects of aging, but worsen others? The truth is that we need more detailed long term data, which could reveal which pathways are affected by inhibition.

Is it the best option?

Targeting myostatin works wonders in promoting muscle growth, but just how effective it is at preventing muscular atrophy with age remains to be seen. It might give you larger muscles, but they may atrophy again later on because of problems with the satellite cells which replenish muscle. It may be that replenishing or improving the health of these satellite stores could actually produce better results.

It's a great start, but for a comprehensive solution we still have to delve deeper and fix the fundamental aging processes in cells that give rise to muscle tissue.

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