Follistatin

Aging is inevitably accompanied by a decline in bone and muscle partly because of the changes of expression of activin A and myostatin in the body.

But, what if science could manipulate the expression of these factors to alter the inevitability of decline? What if there was a way to intervene in the process to stop aging—to maintain and regenerate strong bones and muscles—at a physiological level?

Follistatin could be the key. Follistatin naturally occurs in human bodies and is understood to play a role in both the inflammation processes as well as reproduction, specifically embryo implantation, and more.

Popular as a supplement among elite bodybuilders, Follistatin helps the body to build muscle at a faster rate than weight lifting alone. It does this by blocking myostatin, which is believed to play a role in the signaling of the natural aging process.

Beyond being used as a fringe supplement for bodybuilders, Follistatin has the potential to become an innovative therapeutic for those who suffer from various muscle disorders. While geroscience researchers are still actively studying use cases for Follistatin, some believe this unique protein can potentially alter the physiological process of aging.

What is Follistatin?

Follistatin is a single-chain glycoprotein, or a protein that has sugar molecules attached to it. Notably, follistatin is a binding protein, meaning that its primary function is to bind and bioneutralize members of the TGF-β superfamily, notably activin.

This is critical because the superfamily, as the name might suggest, is super, with functions that influence cell proliferation, differentiation, and migration, in all tissues of the human body.

Activin A, for example, functions to regulate inflammation and immunity. The production of activin A and its binder, follistatin, increases in cases of acute and chronic inflammatory conditions. As the binder, follistatin has the ability to block proinflammatory and profibrotic actions of activin A, leading to follistatin’s potential as a therapeutic option for inflammation and fibrosis.

What is Follistatin 344?

Follistatin 344 is an engineered analogue of naturally occurring follistatin. Researchers have found that Follistatin 344 inhibits myostatin, a key negative regulator of skeletal muscle growth, leading to an increase in muscle mass.

Myostatin is a regulator of adipogenesis, or the process by which fat-laden cells, or adipocytes, turn into adipose tissue, i.e. fat tissue. Myostatin blocks muscle growth, thus muscles don’t rebuild themselves when myostatin levels are high.

Follistatin has proven its ability to inhibit myostatin and, therefore, the ability to increase muscle mass time and time again. In a 2008 study on mice, for example, the one-time administration of myostatin-inhibitor-proteins to both normal and dystrophic mouse models (including aged animals) enhanced muscle mass and strength for more than two years.

In another study in 2009, researchers measured increased muscle mass and strength in monkeys after the injection of a follistatin-producing gene therapy.

In 2020, a study sent mice into space to better understand how to defend against the realities of muscle and bone loss in astronauts. The study demonstrated that targeting the myostatin/activin A signaling pathway effectively protects against both muscle and bone loss in microgravity, suggesting that similar treatments might be effective for disuse atrophy on planet Earth.

Follistatin 344 vs 315

Follistatin 344 and 315 are engineered versions of follistatin as it naturally occurs. Follistatin 344 is the more general form of Follistatin, which “exclusively generates the serum circulating Follistatin 315 isoform of Follistatin.” Follistatin 315 is a more specific variation found primarily in blood circulation.

Follistatin Supplements

Foods that naturally contain folllistatin include soy milk, dark chocolate, blackberries, cocoa powder, soybeans, miso, egg yolks, green tea, and raspberries.

Both Follistatin 344 and 315 supplements are available for purchase online. In addition to boosting muscle, the supplements may also support fertility.

Variations of engineered follistatin that combine follistatin supplement functions (blocking myostatin) with anti-inflammatory and anti-fibrotic effects of activin A antagonism also exist.

Beyond supplements, exercise has been proven to increase systemic plasma follistatin in humans.

Follistatin Side Effects

While no major organs were impacted in the 2009 study on monkeys, the supplement does come with a few potential side effects. Most notably, Follistatin-344 puts users at higher risk for Central Serous Chorioretinopathy (CSCR). CSCR causes the build-up of fluid underneath the center of the retina, which leaks from the blood vessel layer.

Also, not all muscle is the same. Studies in mice have shown variations in wild-type muscles vs those that develop when myostatin levels are manipulated, including faster contraction and relaxation during a single twitch and more type llb fibers, or muscles that “produce rapid, forceful contractions to make quick, powerful movements” and fatigue quickly.

A 2015 study on dogs with muscular dystrophy demonstrated improvement and suggested follistatin might help pediatric patients in the future. Still, as of 2020, clinical trials of myostatin inhibitors including follistatin in pediatric and adult patients with muscular dystrophy have yet to demonstrate functional improvement.