Previously, we read about how inhibiting F-spondin can increase height. F-spondin increases MMP levels, TGF-Beta levels, FGF, platelet-derived growth factor levels, and hepatic growth factor levels. One of the members of the TGF-Beta super family is Myostatin(or GDF-8). TGF-Beta is used to promote differentiation into chondrocytes and osteoblasts(although sometimes Bone Morphogenic Proteins can be used) so it is absolutely needed. But there are several cellular proliferation inhibiting mechanisms of TGF-Beta including Myostatin. But since TGF-Beta promotes cellular differentiation so effectively it is superior for us to target the catabolic genes or counteract the catabolic effects(such as taking Astragalus due to effect TGF-Beta has on shortening telomeres). Creatine may inhibit Myostatin and therefore may be a potent way for natural height increase. Creatine is readily available: Optimum Nutrition Creatine Powder, 600g
First, let's discuss GASP-1:
Regulation of myostatin in vivo by GASP-1: a novel protein with protease inhibitor and follistatin domains
"Myostatin, a member of the TGF\- superfamily, is a potent and specific negative regulator of skeletal muscle mass. In serum, myostatin circulates as part of a latent complex containing myostatin propeptide and/or follistatin-related gene (FLRG). GDF-associated serum protein-1 (GASP-1), contains multiple domains associated with protease inhibitory proteins, including a WAP domain, a Kazal domain, two Kunitz domains, and a netrin domain [is associated with endogenous myostatin in normal mouse and human serum]. GASP-1 also contains a domain homologous to the 10-cysteine repeat found in follistatin, a protein that binds and inhibits activin, another member of the TGF\- superfamily. We have cloned mouse GASP-1 and shown that it inhibits the biological activity of mature myostatin, but not activin. Recombinant GASP-1 binds directly not only to mature myostatin, but also to the myostatin propeptide."
Note that Netrin is involved in axonal guidance providing a link between it and F-spondin which modifies axons. GASP-1 may inhibit Netrin and thereby inhibit commissural axon outgrowth. Now by inhibiting F-spondin you are also inhibiting commisural axon outgrowth. Perhaps, commisural outgrowth of motor axons results in growth reduction.
The other effect of GASP-1 is that it inhibits protease. Protease breaks down peptide bonds that link amino acids together which means that it can break down compounds like Human Growth Hormone(growth hormone is peptide based)!
"Myostatin RNA is produced nearly exclusively in skeletal muscle[so muscular exercise may help bone growth by inhibiting myostatin]. To determine the tissue distribution of GASP-1 mRNA, a 551-bp fragment of GASP-1 was amplified from first-strand cDNA produced from a variety of mouse tissues and staged embryos. GASP-1 appears to be fairly widely expressed, with particularly high expression in skeletal muscle and heart. Significant expression is also seen in brain, lung, and testis. In contrast, liver and kidney express relatively low levels of GASP-1 mRNA. Developmentally, the level of GASP-1 mRNA remains fairly constant, perhaps increasing slightly between d 7 and d 11 of mouse embryogenesis[GASP-1 doesn't seem to be expressed(or at least not as much to mention) in bone, thus again muscular exercise may be needed to stimulate the effects of GASP-1, and the muscular production of GASP-1 may be stimulatory on bone]."
So, muscular exercise has stimulatory effects on height increase by inhibiting myostatin and stimulatory effects on GASP-1 which could be a negative feedback mechanism on HGH by degrading peptide bonds.
"GASP-1 inhibited the activity of BMP-11"<-BMP-11 is very similar to Myostatin genetically but BMP-11 seems to be more necessary than Myostatin. In the study, they managed to inhibit Myostatin exclusively with the IC50 domain but it's unclear whether collateral inhibition of BMP-11 by GASP-1 will be detrimental and whether development will be fine with reduced but not inhibited levels of BMP-11.
Effects of oral creatine and resistance training on serum myostatin and GASP-1
"[We] determine the effect of resistance training for 8 weeks in conjunction with creatine supplementation on muscle strength, lean body mass, and serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1). In a double-blinded design 27 healthy male subjects (23.42 ± 2.2 years) were assigned to control (CON), resistance training + placebo (RT + PL) and resistance training + creatine supplementation (RT + CR) groups. The protocol consisted of 3 days per week of training for 8 weeks, each session including three sets of 8–10 repetitions at 60–70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis (full body DEXA) were performed at 0, 4th and 8th weeks. Myostatin and GASP-1 was measured. Resistance training caused significant decrease in serum levels of myostatin and increase in that of GASP-1. Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin, but had no additional effect on GASP-1. The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation."
Creatine can make you taller by inhibiting myostatin. Exercise can make you taller by inhibiting myostatin and increasing serum levels of GASP-1 which in turn inhibits Myostatin further. GASP-1 can also prevent the breakdown of anabolic hormones like HGH. Lower serum levels of myostatin means lower levels of myostatin for the growth plate. Creatine also may be superior to exercise as GASP-1 additionally inhibits BMP-11 which is needed for proper development.
Activin IIRB is expressed in chondrocytes and the periosteum. "Myostatin mediates its actions through binding to activin IIb receptors"<-So again myostatin has an effect on bone but the main inhibitory factors on myostatin occur with muscle.
"Subjects assigned to the RT + CR group received creatine monohydrate in capsule form (Gensan Abiogen Pharama; Italy) at a dose 0.3 g kg−1 day−1 (divided into three equal doses) for the 1st week (loading period) and 0.05 g kg−1 day−1 (once daily) for the remaining 7 weeks. This supplementation protocol was anticipated to increase muscle creatine levels by 14–28%"<-The dosages used. Creatine inhibits myostatin production of the muscle which has effects on all cell types.
Creatine and Resistance training combined decreased serum levels of Myostatin by about 1/6th(120ng/ml to 100 ng/ml) over 8 weeks. Resistance Training on it's own increased levels of GASP-1 more than Resistance Training plus creatine. Thus, Creatine helped selectively inhibit Myostatin while avoiding GASP-1 induced inhibition of BMP-11.
Creatine would seem to be optimized for height increase during development and during a height increase program like LSJL.