Myostatin, Muscle Loss, and Patching the Symptoms

Most of the potential applications of new knowledge of human biochemistry aimed at treating age-related degeneration are really just patches. They don't aim to address the underlying causes of degeneration, but rather try to paint over the symptoms. If that was all that was possible, then so be it - but research and development in this age of advancing biotechnology has far greater potential.

Needless to say, there is no clear line separating "patch" from "addresses root causes." Causes cascade, and it's not always fully understood why a particular age-related degeneration exists. A good illustration of this sort of uncertainty can be found in the development of therapies to suppress myostatin and so spur muscle growth, work with potential for treating sarcopenia, or age-related muscle loss. From a recent article:

The researchers tried to use one protein called follistatin to impede the action of another, myostatin, that’s known to inhibit muscle growth. They injected the gene for follistatin into the right legs of six healthy monkeys and after eight weeks, their right legs had grown and were larger than their left legs.

"We created a stronger muscle," said Brian Kaspar, the principal investigator for Nationwide’s research institute. "We also showed that the muscle generated more force."

To deliver the gene, the researchers loaded it onto a so- called adeno-associated virus and injected it into the monkeys. This type of virus is designed to be harmless and is commonly used as a delivery vehicle in gene therapy procedures.

Given that natural human myostatin mutants exist, this sort of thing shows promise. More muscle in the old is better than less muscle, but is this just a patch? Will additional muscle fibers in the old be just as damaged and lacking in strength as those grown without the influence of myostatin? Interestingly, this isn't a straightforward question, as myostatin appears to work through regulation of satellite cells:

In young mice, lack of myostatin resulted in increased satellite cell number and activation compared to wild-type, suggesting a greater propensity to undergo myogenesis, a difference maintained in the aged mice. ... In conclusion, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity.

Satellite cells are progenitor cells that build muscle when activated, and their activity declines with age. There is an ongoing debate as to whether this decline - and resulting loss of muscle mass and strength - is due to a reduction in the size of the satellite cell population, or whether the population is still large and capable of action, but other age-related changes in biochemistry block the activation of these progenitor cells. Or both. If the latter situation is largely the case, then manipulation of myostatin starts to look a little less like a patch, and a little more like aiming at root causes - boosting the activity of a cell population that is being recalcitrant. But this doesn't address the layer of causes below that; why age-related changes in our biochemistry cause stem cells to stop working.

The path to the future I'd like to see result from modern biotechnology is a passage from the strategy of patching symptoms to the strategy of addressing root causes. This is a move from present-day inefficiency - and therapies that only postpone the inevitable age-related breakdown of our biochemistry - towards efficiency and the ability to completely prevent age-related degeneration.

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