Recently, I read on a forum about these young Korean kids who are given some type of small green type pill by their mothers to help them grow taller. It is interesting that there is such stuff being sold for at least the last 30 years which supposedly would help young Asian kids grow taller.

Maybe the competitive nature of these East Asian cultures makes mothers try all sorts of rather bizarre things to help give their children any type of edge in life.

In the last two years of research, I personally have found at least 2 other different compounds which have been a part of Traditional Korean Medicine who has been believed to work in helping kids grow taller. Not only that, a group of Korean scientists filed a patent on a type of Ultrasonic-LED Combo type device which was supposed to stimulate the epiphyseal plates. It seems that South Korea, which has taken much of the older medical knowledge from Traditional Chinese Medicine, might have figured out a few natural ways to help its people end up slightly taller.

All this talk about Eastern Mysticism and the Esoteric made me wonder whether the Oriental Superpower Plant known as the Ginseng might have any type of chondrogenic or cartilage enhancing properties. After taking some time to look over PubMed, there were at least a couple of studies which validates this idea.

• Ginsenosides from Korean red ginseng inhibit matrix metalloproteinase-13 expression in articular chondrocytes and prevent cartilage degradation.
• Anti-apoptotic Activity of Ginsenoside Rb₁ in Hydrogen Peroxide-treated Chondrocytes: Stabilization of Mitochondria and the Inhibition of Caspase-3
• Effect of Ginseng Saponin on Human Chondrocyte.
• Ginsenoside Rb1 prevents interleukin-1 beta induced inflammation and apoptosis in human articular chondrocytes

The active ingredient in all of the varieties of Ginseng, is this compound known as ginsenosides, which is in a category of compounds known as the saponin ,or more specifically the triterpenoid saponins. (For more information on Ginsenosides, refer here.) By last count, there is over 150 different kinds of Ginsenosides. From thousands of years of trial and error, humans found that they can orally consume the Ginseng and get the active ingredient inside the Ginseng to work. The Ginsenosides work in the stomach through acid hydrolysis and in the gastrointestinal tract by the reaction bacterial hydrolysis.

It seems that at least three of the over 150 different kinds of ginsenosides have some type of cartilage enhancing ability. I am quite sure that in the last century, multiple Asian researchers have validated the idea that whatever is in ginseng have anti-inflammatory effects. Inflammation is really the start of almost all types of cartilage degradation. If Inflammation is prevented, then the chances of the onset of osteoarthritis is going to be severely reduced.

In the first study, 11 different types of ginseng saponins were used. There were 2 which had some really powerful effects, ginsenosides F4 and Rg3. It is F4 which is really interesting. With increased dosage/concentration of the F4, the inhibition of the MMP-13, which is a collegenase, was increased, almost linearly in fashion. at 50 microMolars, the inhibition of not just the MMP-13, but also the p38 MAPK Pathway was also inhibited.

In the third study, it was found that the saponin was able to cause the number of chondrocytes in deficient mediums to proliferate and have the precursor stem cells to differentiate into chondrocytes{I believe that it was stating that it encourages differentiation of chondrocytes as in chondrocytes into hypertrophic chondrocytes not differentiation of stems into chondrocytes-Tyler}.

This is really interesting because for the longest time, many “grow taller pills” that were sold in places in South Korea (and maybe also China, Taiwan, Singapore, etc.) did have extracts of at least a little bit of ginseng in them. Is it really that far fetched for people to believe that the mystical ginseng plant would have some “special” ingredient that would also make them taller?

In the article “South Korea Stretches Standards for Success” published back in Dec. of 2009 in the New York Times, there was a really popular clinic called Hamsoa, which supposedly had already 50 clinics around South Korea, and they gave kids a special type of tonic which was supposed to be taken twice a day. Inside that tonic, was deer antler, ginseng, and other chemical compounds at a much lower concentration. Notice that deer antler and ginseng were mentioned.

It might be possible to use the ginseng to stimulate the activity in the growth plates of young kids, as well as even use the deer antler, but I am not sure how pronounced the stimulation would be. What can be well substantiated is that ginseng seems to help prevent cartilage degeneration and regular chondrocyte apoptosis.

If it is possible to gain disc height by stretching. that could potentially explain the height gain of programs like agrobics.  Unfortunately, this batch of research I found, does not produce a strong link between stretching and height gain.  Mainly due to the nucleus pulposus being mechanically fragile.

The structural basis of interlamellar cohesion in the intervertebral disc wall.

“The purpose of this study was to investigate the structural mechanisms that create cohesion between the concentric lamellae comprising the disc annulus.”

” Additional bulk samples of annulus were fixed while held in a constant, radially stretched state in order to investigate the potential for interlamellar separation to occur in a state more representative of the intact disc wall. ”

“[IVD] tissues generally exhibit highly non-linear stress–strain responses, with the low-stress phase being a direct consequence of large-scale reversible alterations occurring in their fibrous architecture.”

“Fully relaxed, hydrated interlamellar section showing adjacent lamellae as both in-plane (IP) and cross-sectioned (CS) arrays. Note the compartmental division between the cross-sectioned bundles at Z.”

Here you can show the possibility that stretch can potentially lengthen the IVDS.

“(A) Interlamellar section subjected to radial stretching and revealing various modes of interconnection; (B) detail of radial bridging element passing between the cross-sectioned bundles; (C) detail of more uniformly distributed linking elements between adjacent lamellae.”<-This is radial stretching which should increase disc width rather than length.

“Interlamellar section radially stretching [causes] progressive fragmentation of cross-sectioned bundles ”
“Interlamellar section subjected to tangential stretching. Selective fibre bundle pullout at grip ends has induced a substantial degree of shear between the in-plane arrays, thus revealing further the extent to which bridging elements (BE) pass between the cross-sectioned bundles and connect the neighbouring in-plane arrays (IP).”<-So fibre bundles pull out and bridge elements form resulting in possible overall lengthening in response to stretching.

“With increased stretching the forces transmitted by these same interconnections resulted in a progressive fragmentation of the cross-sectioned bundles involved.  [Fragments  separate] from [their] parent cross-sectioned bundle (CS).”

“the overall morphology of the permanently stretched samples reveals a radial elongation of the cross-sectioned bundles”<-but this is disc width and not height.

This study illustrates a possible mechanism of increasing interverterbral disc height although it’s possible that disc height could be still limited by mechanisms not investigated in this study.

Here’s a study that investigates the effects of twisting directly on the entirety of the spine:

Low back pain development response to sustained trunk axial twisting.

“The trunk axial twisting was created by a torsion moment of 50 Nm for 10-min duration.”

“The results showed that there was a significant  twist creep with rotational angle 10.5° as well as VAS increase with a mean value 45 mm{how would this effect spine height?}. The erector spinae was active in a larger angle during flexion as well as extension after trunk axial twisting.”<-creep implies a change in shape but whether that change involved a longitudinal increase is unclear.

“the elastic forces generated by the passive component of muscles are the main sources of passive resistance at the initial twisting motion, and then toward the end of ROM lumbar posterior ligaments and IVD will start to generate elastic forces and become the main contributor. This finding suggests that prolonged trunk axial twisting could also generate passive tissue creep and cause an alternation in the synergy between lumbar active and passive tissues.”

” The shear forces and moment created by spinal twisting within discs might elicit a shrinkage on spine by making the nucleus pulposus loose some fluid just like twisting a cloth full of water.”<-however this could also make the spine adapt by developing methods to absorb and retain more water.

Here’s a look of individual IVD cells response to loading regimes:

Region specific response of intervertebral disc cells to complex dynamic loading: an organ culture study using a dynamic torsion-compression bioreactor.

“We applied four different loading modalities [1. control: no loading (NL), 2. cyclic compression (CC), 3. cyclic torsion (CT), and 4. combined cyclic compression and torsion (CCT)] on bovine caudal disc explants”<-combined torsion and compression would be most akin to stretching as when you stretch one way you’re compressing another.

“In the CCT group, less than 10% nucleus pulposus (NP) cells survived the 14 days of loading, while cell viabilities were maintained above 70% in the NP of all the other three groups and in the annulus fibrosus (AF) of all the groups.”

“Gene expression analysis revealed a strong up-regulation in matrix genes and matrix remodeling genes in the AF of the CCT group”<-maybe developed of the extracellular matrix could increase height?

“Daily cyclic loading is important for disc health, as it assists in the transport of large soluble factors across the disc and from its surrounding vascular supply and applies a direct and indirect stimulus to disc cells.”<-This would increase height but does stretching apply a stimuli further than that?

” Characteristics of DD include increased cell death, a decrease in disc height due to a loss of essential matrix components which can also be reflected by an increased matrix catabolic gene expression (MMP-3, MMP-13, ADAMTS-4) but decreased anabolic gene expression (collagens and proteoglycans), increased inflammatory response (TNF-a, IL-1b, IL-6) and changes of mechanical properties of the disc (increased stiffness)”<-Although some of these things could also be involved in a anabolic protocol but the main thing we should watch is loss of essential matrix components in terms of reducing height.

“During the day, the disc experiences a pressure range from 0.1–1.1 MPa . However, studies have shown that dynamic compressive loading of >0.8 MPa could induce early DD; dynamic loading of physiological magnitude (1 MPa) at a frequency of 0.2 Hz was suggested to be the best in preserving disc metabolism while a frequency of 0.01 or 1 Hz could stimulate catabolic gene expressions ; signs of mild disc degeneration were seen when loading was applied in a longer term of 8 weeks (8 h/day) even at a physiological magnitude (1 MPa). The complex loading of side bending (in the form of asymmetric compression) and cyclic compression induced a greater structural disruption to the disc than simple cyclic compression”<-This would suggest that the best way of being as tall as possible would be to avoid excessive stimulus.

” torsional[twisting] injury is one of the initiators of disc degeneration, as evidenced by a decrease in disc height and a drop in disc proteoglycan content”<-so getting injured while stretching could possible reduce height.

“cyclic torsion could cause injury to the disc, provoking increased inflammatory (TNF-α and IL-1β ) and altered elastin gene expressions. An increase in elastin content in the AF is one of the observations in degenerated human discs and an alteration in the elastin fiber network might render the AF more susceptible to micro failure under torsion and bending”

“asymmetric dynamic compression (bending with compression) caused annulus fibrosus (AF) delamination and cell apoptosis”

“Discs used in this study had a mean dimension of 16.63±1.55 mm diameter and 9.58±1.22 mm height at day 0. By the end of the experiment, disc volume was increased by 10±5.76% for NL[no load], but increase in disc volume were less than 2% in all the other groups with loading”

“There was a slight increase in mean disc height of around 3% in the NL and CT[cyclic torsion/twisting] groups, while disc height was decreased by about 2% in the groups with cyclic compression (CC and CCT).”

“In the NP, collagen 1 expression was significantly up-regulated in CT. ADAMTS-4 was increased over 1000 fold in both CT and CCT, where its inhibitor TIMP-3 was also increased more than 10-fold”

” In the transition zone between the cartilaginous endplates (EP) and the nucleus pulposus (NP) , cells stayed as chondrocyte-like cells (indicated by black arrows) in the CC and CT groups with a round cell nucleus surrounded by lacunae. However, in CCT, very few cells stayed as chondrocyte-like cells in the cartilaginous endplate and cells right across the endplate region changed to spindle-shaped  and the cell lacunae and the cell boundary were lost.”<-This could be a key to height growth.  Maybe one way to restore growth plate is to remove either compressive or torsion forces in the bone.

You can definitely see the loss of cartilage but is it an irreversible loss?

“torsion-compression loading has caused micro-damage to the collagen, therefore disc cells have been activated to compensate for the destruction. As shown in the gene expression result, groups with torsion (CT and CCT) showed a larger increase in both anabolic and catabolic gene expression by AF cells as compared to no loading or pure compression, indicating that AF cells were more sensitive to torsional loading stimulation. Therefore they responded by increasing some matrix production and matrix destruction enzymes to remodel the matrix environment.”

“One possible reason for the difference in response between the NP and AF to the same loading is due to the fundamental difference in the matrix component and structure between NP and AF. AF collagen fibers are aligned in an angle that can withstand shear force but the disorganized gel-like matrix of the NP cannot withstand a high shear force under combined compression and torsion. The NP, which is mainly composed of water, proteoglycans and collagen 2, is more resistant to compressive force than direct shear force as in compression and torsional load. A uniform torque applied to the disc will result in a hoop strain within the tissue, which increases with the distance from the center of rotation. It might be that the reaction of the annulus cells to the applied torsion stress is also different between the outer annulus and the inner annulus fibrosus as the inter-lamellar angle decreases radially from the periphery to the center from 60° towards 40°. Moreover, the elastic fiber arrangements in intra-lamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the AF matrix structural hierarchy”

My Personal Analysis On Tyler’s Claims On His Finger Bones Lengthening

So Tyler has asked me to do an exact measurements on the length of his fingers for about a month now. I finally got the time to stop by the local FedEx and asked them to print a blown up copy of all the X-rays that he has shown in previous posts. I chose the option of 24″ x 36″ and printed out all 5 of the pictures, all black and white. I took the prints home, cut out the edges, and checked the length unit standards at the bottom. When I looked at the centimeter scale, which is very much like a map legend, of the X-rays for the left and right hand, they matched EXACTLY. That means that making conclusive conclusions is much easier. I don’t need to multiply by some factor like 1.15 to make the lengths of one of the X-rays to match up to the other X-Ray to work out.

How I prepared the analysis

So I folded the blown up 24″x36″ picture of the X-ray of the right hand on the axis which is parallel to the right index finger. I placed the finger bones right next to each other.

I then used a US Based measuring tape and started to check the length of the bones at the exact center.

Here is what I did find

Based on at least have a dozen extremely, almost anally, specific measurements done on the center of the proximal part of the index finger for both left and right, here is what I found…

On the right index finger, in the proximal finger bone, it is only slightly longer than the left one. How small do I mean by “slightly”? First, the 24″x36″ blown up picture has the length scale at the bottom. Comparing the inches on my measuring tape to the scale, it seems that…

1 cm of the blown up is exactly = what is almost exactly in the middle between 7/8th and 15/16th of the inches of my measuring tape (aka 29/32th) —-> 1 cm = 29/32 inch

Length of the right index finger (measured from proximal end point to end point) – 3 and 9/16th of an inch

Length of the left index finger (measured from proximal end point to end point) – between 3 and 9/16th and 3 and 19/32th of an inch

Sometimes (maybe half of the time) the measurements of the left and right hand index fingers are exactly the same, but the other half of the time, the left index finger is slightly longer, but by maybe just 1/32th of an inch on my measurement tape.

Doing a little bit of converting of the units (and then canceling out the inches terms), we get…

 (1 cm)/(29/32 inch) X (1/32 inch) = 1/29 cm = .34 mm or a little over 1/3rd of a mm

The Result

After half an hour of measuring the same two parts over and over again, being a little too anal over the length, The conclusion is that the proximal bone in the right index finger is around 1/3rd mm longer than the one on the left.

Note: About half of the time I did the measurement, it does seem like that the length measurements for the left and right index fingers were exactly the same. The other half of the time, the right one was just slightly longer than the left one (usually just 1/32rd of an inch of the tape I had). At no measurement did I ever find that the left one was slightly longer than the right index finger, at least for the middle bone part.

What else did I find?

It seems that the most significant difference in length is at the tip of the fingers, on the distal end. The very small distal bone at the tip of the right index finger always seems to be slightly longer than the left one.

• The length of the distal end of the right index finger = 1 and 1/2 inches
• The length of the distal end of the left index finger = 1 and 15/32th inches

The suggest that there is a difference in the tips of the index fingers, by around 1/3rd of a mm.

Further Analysis

At this point, the results show only that 50% of the time when I would do a measurement, it seems that the most proximal phalanges of the right index finger is only about 1/3rd a mm longer than the left one. Based on those results, I would say that the difference can not be used as evidence that the bones in Tyler’s index fingers actually increased in length.

I did not take any statistics & probability courses back in university so I would not be able to do any type of statistical analysis. However, I can put things into perspective.

On average, the length of that specific bone is around 3 and 9/16th inches at the middle, measured from tip to tip. That converts to 3.5625 inches X ( (1 cm)/(29/32 inch)) = (3.5625*0.90625) = 3.2285 cm

That is the length of each of these bones. Divide the 1/3rd of a mm by 3.2285 cm and we find that the difference in length between the two bones being of opposite hands is just at 1% difference. If my measurements are right, then the right finger at least at the proximal one, is maybe 1% longer than the one on the left.

Osteocyte-secreted IGF-1 may manipulate height growth via IGFBP secretions but this would only have an effect on adult individuals if IGFBPs could induce chondrogenesis on their own.

Role of Osteocyte-derived Insulin-Like Growth Factor I in Developmental Growth, Modeling, Remodeling, and Regeneration of the Bone.

“Osteocytes secrete large amounts of insulin-like growth factor (IGF)-I in bone.”

“a regulatory role for osteocyte-derived IGF-I in the osteogenic response to mechanical loading”

“transgenic mice with ablation[removal] of osteocytes were unresponsive to unloading and had an impaired mechanotransduction”<-For more on this study see below.

“The long bones of transgenic mice with overexpression of IGF-I in bone showed enhanced osteogenic response to in vivo mechanical loading.”<-thus release of IGF-1 by osteocytes could be a key mediator of loading on bone shape.

“Conditional disruption of Igf1 gene in osteocytes blocked the loading-induced expression of early mechanoresponsive genes, i.e., cyclooxygenase-2 (Cox2), Igf1, and c-Fos”

“ince conditional deletion of Igf1 gene in hepatic cells, which reduced circulating IGF-I levels by >75%, had no effects on bone length and size, but targeted disruption of Igf1 gene in mature osteoblasts or chondrocytes greatly reduced bone length and size without affecting the circulating IGF-I level, it appears that locally produced bone-derived IGF-I, and not the circulating liver-derived IGF-I, is essential for the developmental bone growth.”

“the osteocytes-derived IGF-I-dependent regulation of longitudinal bone growth may involve osteocyte-derived soluble factors. A potential candidate is the IGF binding proteins (IGFBPs). IGF-I has paracrine effects on bone cell production of IGFBPs, and many IGFBPs have IGF-dependent and -independent actions on bone turnover.  Changes in Igf1 expression in a number of cell types have been associated with alterations in the IGFBPs expression profile. For example, target disruption of Igf1 in chondrocytes reduced IGFBP5 expression in the growth plate cartilage. Conditional disruption of Igf1 in mature osteoblasts decreased bone levels of IGFBP3 and IGFBP4. Conversely, conditional disruption of Igf1 in osteocytes increased plasma IGFBP3 level and decreased plasma IGFBP5 level, raising the intriguing possibility that the reduced bone production of the stimulatory IGFBP5 and the increased bone production of the inhibitory IGFBP3 in osteocyte conditional KO mutants may in part contribute to the reduced longitudinal bone growth.”

“The osteocyte Igf1 conditional KO mice [has] 8-12% shorter bone length and small bone size”

Since part of the LSJL hypothesis is that LSJL has a greater effect than normal.  Let’s examine the study which found that removal of osteocytes dapened mechanical loading.

Targeted Ablation of Osteocytes Induces Osteoporosis with Defective Mechanotransduction

“Following a single injection of DT, approximately 70%–80% of the osteocytes, but apparently no osteoblasts, were killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity and microfractures, osteoblastic dysfunction, and trabecular bone loss with microstructural deterioration and adipose tissue proliferation in the marrow space, all of which are hallmarks of the aging skeleton. Strikingly, these “osteocyte-less” mice were resistant to unloading-induced bone loss”

Here’s an image that shows the impact of osteocyte ablation on mouse growth plates:
Tg+Dt A shows the growth plate of mouse with less osteocytes.  You can see that it is more disorganized but whether it affects longitudinal bone growth is unclear.  In E is an image of a vertebrae and the ablated osteocyte bone may be shorter by eyeballing it.

Here’s an image of the scattered growth plate in the ablated osteocyte bone:

GP standing for growth plate.

So, osteocyte IGF-1 contributes to longitudinal bone growth at least by increased organization.  Since increased organization was not apparent in LSJL growth plates, it is still likely that LSJL can stimulate height by a method not available via typical mechanical loading.

Epigenetic manipulation refers to changing genetic expression of certain genes(in this case height increasing genes) via nutritional or mechanical means.  This manipulation can occur by altering histones, chromatin folding, methylation, telomere length, etc.

The paper below indicates that altering epigenetics can powerfully influence but the question is how to determine the mechanical and nutritional methods that can influence these genes.

Epigenetic heredity of human height

“Genome‐wide SNP analyses have identified genomic variants associated with adult human height. However, these only explain a fraction of human height variation, suggesting that significant information might have been systematically missed by SNP sequencing analysis. A candidate for such non‐SNP‐linked information is DNA methylation. Regulation by DNA methylation requires the presence of CpG islands in the promoter region of candidate genes{So any height increase genes that have CpG islands can be altered by DNA methylation}. Seventy two of 87 (82.8%), height‐associated genes were indeed found to contain CpG islands upstream of the transcription start site, which were shown to correlate with gene regulation. Consistent with this, DNA hypermethylation modules{hypermethylation can result in transcription silencing which can be inherited by daughter cells(a daughter is the cell formed by mitosis)-mitosis occurs in the growth plate most heavily in the proliferative zone} were detected in 42 height‐associated genes, versus 1.5% of control genes, as were dynamic methylation changes and gene imprinting. Epigenetic heredity thus appears to be a determinant of adult human height. Modulation of DNA methylation are candidate to mediate environmental influence on epigenetic traits. This may help to explain progressive height changes over multiple generations, through trans‐generational heredity of progressive DNA methylation patterns.”

Some height increase genes identified in multiple studies:

(ACAN, BCAS3 also known as TBX2, EFEMP1, HHIP, HMGA1, HMGA2, LCORL, NCAPG, PLAGL1, PTCH1, SOCS2, SPAG1, UQCC also known as GDF5, ZBTB38, ZNF678)

“Genes close to the SNP most strongly associated with body size were shown to encode extracellular matrix components, proteases, cell cycle controllers, transcription factors and signaling molecules”

Table 1 in the paper gives a list of height related genes.  Here’s a list of genes related to height increase and whether you want to upregulate or downregulate the genes relative to height increase.

“Functionally‐relevant DNA methylation patterns were thus candidates to be associated with adult stature subgroups in addition to DNA sequence variants. Functionally‐relevant DNA methylation patterns may affect selective mechanisms, thus behaving as true hereditary traits. Consistent with this, a metastable epigenetic heredity of the DWARF1 locus was shown to affect plant size and this phenotype was inherited through mitosis and meiosis”

“DNA methylation patterns can keep record of the nutritional status and affect, in turn, morphometric parameters. Modifications of DNA methylation patterns in growth‐related genes can be inherited trans‐generationally, through incomplete erasure of epigenetic patterning in the germline.”

“Genomic imprinting defects are associated with developmental disorders, including Silver‐Russell, Beckwith‐Wiedemann, and Prader‐Willi syndromes. Genomic imprints are affected by environmental factors, and also associate with several human cancers.”

“Proteins are represented as nodes (hubs), the biological relationships between the nodes (edges) are represented as lines. Height‐associated proteins are in red; linker proteins are in white; miRNA are in gray. Major hubs are in magenta; SMAD isoforms are in blue.”

“72 of 87 height‐associated genes (82.8%) were found to contain at least one CpG island in the 2,000 bp upstream of the transcription start site (TSS) (99 CpG islands overall) . Notably, in all CpG islands‐associated height genes, CpG islands overlapped with the TSS, supporting an actual regulatory role in gene transcription”

Notable genes regulated by DNA Methylation according to Table 2 include: BMP2, BMP6, and SOCS2 as well as several not normally associated with height increase.  Notable genes regulating DNA Methylation(that is the control the methylation status of height related genes) include: DNMT3A, DOT1L, HMGA1, HMGA2.

“five genes (ACAN, ANKS1, FBP2, NACA2, ZBTB38) were found to have no evidence of DNA methylation. The remaining genes (94.3%) were shown to undergo broad changes of DNA methylation levels across experimental conditions”

“CpG island methylation in the BMP2 promoter causes loss of BMP‐2 protein expression in transformed cells{You would NOT want this if your desire was to have your child grow taller}. Shut‐down of the BMP6 gene by promoter methylation was observed in malignant lymphomas”

“c‐Myc regulates at least seven height‐associated genes (CDK6, COIL, HMGA1, LIN28B, RBBP8, RPS20, TRIM25/EFP), and its binding to genomic loci is dependent on chromatin structure and CpG methylation.”

“The Beckwith‐Wiedemann syndrome is caused by deregulation of imprinted genes within the 11p15 chromosomal region, i.e., KIP2, H19 and LIT1, whether alone or as interacting regulatory units . Hypermethylation at the 11p15 telomeric imprinting control region (ICR1), are observed in about 5 to 10% of affected patients. Both H19 and LIT1, which encode untranslated RNAs, and IGF2 are either maternally imprinted genes with growth enhancing activity or paternally imprinted genes with growth suppressing activity.”

“Affected children reach an average height of 2.5 SD above the mean at or after puberty, and their growth velocity is above the ninetieth percentile until 4–6 years of age.”

“Up to 60% of cases of Silver‐Russell [dwarfism] syndrome are caused by hypomethylation at the ICR1 on chromosome 11p15, involving the H19and IGF2 genes”<-so underexpression of ICR1 is good for height and overexpression of ICR1 is bad for height if hypermethylation transcriptionally silences expression and hypomethylation increases it.

“c‐Myc regulates the cell cycle, and plays a major role in cell growth during interphase, by regulating genes required for the production of energy and metabolites. The c‐Myc network widely interacts with those driven by other major hubs. c‐Myc is repressed by transforming growth factor β (TGF‐β) through the binding of SMAD3 to the MYC promoter. p53 represses c‐Myc through the induction of the tumor suppressor miR‐145. c‐Myc amply interacts also with the ER network: almost all of the acutely estrogen‐regulated genes with roles in cell growth are c‐Myc targets. Notably, estrogen‐mediated activation of rRNA and protein synthesis depends on c‐Myc. Equally c‐Myc dependent is the estrogen‐induced suppression of apoptosis caused by growth factor deprivation”

“p53 regulates the expression of target genes that modulate chromatin structure and function, cell growth, aging and apoptosis. p53 interacts with components of multiple different histone remodeling complexes, including CBP/EP300 (CBP/p300), GCN5, PCAF, and SETD7 modifying histones at the promoters. p53 also controls DNA methylation levels, and that this affects genome stability”

“ERα regulates at least eight height‐associated genes (BCAS3, BMP2, BMP6, DCC, GLT25D2, PENK, RBBP8, TRIM25/EFP).”

“ERα blockade diminishes the secretion of endogenous growth hormone, the key hormone regulator of linear growth in childhood. This action is mediated by SOCS‐2. The ERα network widely interconnects with the p53, Hh and BMP/TGF‐β pathways. p53 regulates ER expression through transcriptional control of the ER promoter”