Reviewing Myostatin in Muscle Growth, and Efforts to Produce Myostatin-Targeted Therapies

Myostatin is one of the better targets for enhancement therapies from the point of view of feasibility and existing data on its effects. Myostatin suppresses muscle growth via intracellular signaling. A range of possible methods exist to interfere in this process, some of which have been trialed in human patients: reducing production of myostatin, binding to circulating myostatin with antibodies to ensure clearance, preventing myostatin from binding to cell surface receptors in other ways, upregulation of follistatin, an antagonist to myostatin, and so forth. Myostatin loss of function mutants, natural and artificial, exist for a range of mammalian species, including humans. Beyond a much greater than usual muscle growth, there do not appear to be obvious long-term issues in these individuals.

Current research findings in humans and other mammalian and non-mammalian species support the potent regulatory role of myostatin in the morphology and function of muscle as well as cellular differentiation and metabolism, with real-life implications in agricultural meat production and human disease. Myostatin null mice (mstn-/-) exhibit skeletal muscle fiber hyperplasia and hypertrophy whereas myostatin deficiency in larger mammals like sheep and pigs engender muscle fiber hyperplasia. Myostatin's impact extends beyond muscles, with alterations in myostatin present in the pathophysiology of myocardial infarctions, inflammation, insulin resistance, diabetes, aging, cancer cachexia, and musculoskeletal disease.

In this review, we explore myostatin's role in skeletal integrity and bone cell biology either due to direct biochemical signaling or indirect mechanisms of mechanotransduction. In vitro, myostatin inhibits osteoblast differentiation and stimulates osteoclast activity in a dose-dependent manner. Mice deficient in myostatin also have decreased osteoclast numbers, increased cortical thickness, cortical tissue mineral density in the tibia, and increased vertebral bone mineral density. Further, we explore the implications of these biochemical and biomechanical influences of myostatin signaling in the pathophysiology of human disorders that involve musculoskeletal degeneration.

The pharmacological inhibition of myostatin directly or via decoy receptors has revealed improvements in muscle and bone properties in mouse models of osteogenesis imperfecta, osteoporosis, osteoarthritis, Duchenne muscular dystrophy, and diabetes. However, recent disappointing clinical trial outcomes of induced myostatin inhibition in diseases with significant neuromuscular wasting and atrophy reiterate complexity and further need for exploration of the translational application of myostatin inhibition in humans.

Link: https://doi.org/10.3389/fgene.2021.662908

Comments

If myostatin causes all of these problems with the skeletomuscular system, why does this compound exist in our bodies in the first place? What role does it play?

Posted by: Abelard Lindsey at April 28th, 2021 9:59 AM

Myostatin inhibition will also make it possible for people to live healthily in low gravity environments such as Mars and possibly the Moon and Titan.

Now its on to building radiation resistance....

Posted by: Abelard Lindsey at April 28th, 2021 10:01 AM

According to Mucle & Fitness magazine, " large pharmaceutical companies continue to fail in their efforts to produce even a single viable prescriptive myostatin inhibitor for patients."
https://www.muscleandfitness.com/flexonline/flex-nutrition/myostatin-inhibition/

Short of plunking down a million bucks for offshore gene therapy, what would be the best bet to injest or inject to tame down this scrouge which keeps increasing as we age?

Posted by: august33 at April 28th, 2021 9:06 PM

It's confusing

https://link.springer.com/article/10.1007/s11357-021-00322-4#ref-CR76

"Whether elevated myostatin expression with advancing age is a function of ageing per se or a product of age-associated physical inactivity, systemic inflammation, or nutritional status remains poorly investigated. Interestingly, muscle myostatin mRNA was found to be lower in both ambulatory and non-ambulatory elderly women than young women"

Posted by: august33 at April 28th, 2021 9:33 PM

@august33
'What would be the best bet to injest or inject to tame down this scrouge which keeps increasing as we age?'
Right now probably YK11: https://pubmed.ncbi.nlm.nih.gov/33588136/
It comes with his own set of problems, though.

I don't think myostatin inhibition is really the way to prevent sarcopenia and such.
Myostatin's main role is probably to prevent the body from accumulating too much energy expensive tissue, i.e. muscle. That's not a problem in sarcopenia patients. Muscle stem cell depletion, diminished excercise capacity, destroyed androgen hormone levels, inflamed joints and broken neurosignaling to the muscle's motor units are targets worth getting after.

Posted by: Jones at April 29th, 2021 12:40 AM

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