Monthly Archives: September 2014

How much can you increase a child’s height with epigenetic manipulation?

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.”

Height gene network

“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”

The Connection Between The Short Stature Of The Vietnamese and Their Diet

I might be stepping out of line with this post but a recent video I saw on Youtube made me wonder whether a certain tribe or ethnic group’s diet and eating habits might have a much larger influence to the height of a certain ethnicity.

I refer to the trip Gordon Ramsey takes to Vietnam in one of his Great Escape episodes. In the last month, I have started to enjoy many cooking channels, and Gordon is a very colorful, interesting character to follow. I don’t have a TV so I don’t know what is really popular on TV these days. It seems that this series of food traveling show has been around since 2010, and only now have I heard of it.

What really struck me was that in the episode where Gordon visits the country of Vietnam, two different people both talk about the lack of calcium in their diet. First, it was Mrs. Vi Ching and 2nd was the guy who Gordon was eating snake hearts with.

It is interesting that this Mrs. Vi Ching, who supposedly owns 4 of the most famous and well touted restaurants in all of Ho Chi Minh City and goes shopping twice a day for freshness made the offhanded comment that “We have no dairy, so we eat the bone for calcium”. Then when Gordon is out with a couple of the vietnamese men, the restaurant chef would fry up the backbone of the snake they ordered which was made into at least 4-5 different dishes. It was supposed to give them more calcium.

Refer to the video below…

So it seems that for the people in Vietnam who really focus on the food, they have a unique concern with Calcium and getting enough of it. Do they somehow realize that their diet intrinsically lacks the calcium (as well as the Vitamin D, K2, Iron, Amino Acids) that is needed to grow “normal”? Or maybe at least by American standards

In my personal life and my history of going to the various Vietnamese Restaurants, I do sort of see the connection. The Vietnamese do eat a lot of strange animals and delicacies, like frogs and snakes, which had a lot of lean, dark, and flavorful meat. The Vietnamese really care about Flavor and Texture, since the 2nd guy also made the comment that the Vietnamese prefer to eat food that has a little bit of chew to them. They focus on taste, but not utility and function. They eat what tastes good, but forget to eat what might be actually good for them and their bodies. They don’t seem to have that critical factor of dairy. Dairy is missing in their diet.

They might be eating cow and beef, but those are used sparingly. They eat shrimp, but there is little excess meat in their diet. The Vietnamese seem to traditionally like to eat out a lot, at the local Hole In the Wall, which are very cheap. That means that the food might not have the neccesary composition (vitamins & minerals) to give them to grow to their maximum potential. I mean, how nutritious can a Flying Bat or Snake be in terms of real nutrition?

So then, why is it that the Vietnamese are not consuming much dairy products? 

I don’t know. Maybe the forests of Vietnams have not been cleared out to make room for cows to graze in, unlike say the USA or Canada, which has a lot of available land. I don’t know what is the average native vietnamese person’s diet, and how much milk they were drinking when they were children who were still growing.

So some might ask me, does that mean that eating a lot of dairy like milk and cheese with higher than average calcium levels would make themselves taller? My previous research into this suggested that there is a positive correlation but the correlation is very weak. Even the 1-2 studies which support that positive correlation didn’t explicitly state out right that there was a positive correlation, but implied it.

Of course, I could , playing my own Devil’s Advocate, show that the Mongolians, who have no source of seafood, vegetables, or fruits, and live off of a diet of just meat (mainly sheep and goat) and dozens of derivatives of dairy products don’t seem to be shooting up like redwoods. I don’t hear about too many 7 foot tall Mongolians that are trying to get into the NBA.

Most people who analyze the factors which make up an individual’s height says that genetics has around a 60-80% effect on a person’s height. Traditionally, the idea proposed by geneticists is that if you are born to short parents or into what has been considered a short “ethnicity”, then there is nothing you can do about it especially in terms with changing one’s diet.

However, there has been multiple times in the last half decade where I have seen cultural trends which suggest that maybe diet and environment may play a much bigger role than believed.

I remember one time in a shopping center and two super tall females walked by me. Both of them were carrying 1 gallons of milk in each of their hands. When I commented them on their purchases of so much milk, one of the girls commented that where she is from, their diet strongly emphasizes dairy problems. I would found out after asking where she was from that she and the other girl were from an unknown city in Germany. Of course, I know from experience that not all full blooded German ethnic girls are above average in height or consume a lot of milk. It might have been just one unique case.

What I can’t write off is this phenomena seen in Denmark, the Netherlands and other Northern European nations where the standard of living is so good. We know from observation that it seems that “Asian” people are stereotupically shorter than say the “Average White American”. However, many sociologists point out that the difference in height is due to them being usually 1st generational immigrants. When these immigrants have children in their new country, with a better diet and healthcare system, the 2nd generational kids turn out to be much taller than them.

That is the phenomena seen in the Netherlands and Denmark, when babies are born of immigrant parents from say Turkey, Iraq, Egypt, Iran, etc end up MUCH taller than what was expected of them by their parents, who might be a little over 5 feet tall. The change in stature by just 1 single generation is staggering! . I don’t disagree that compared to the 100% in blood Ethnic Dutch, the Turkish Immigrants or say a Filipino immigrant might be much shorter on average. What happens almost always is that the immigrant’s kids turn out to be much taller. The height difference is reduced dramatically.

Sure, there is probably not going to be a way to test this out, with a set of identical twins, one raised in native Turkey or Iran, and the other twin living in Amsterdam, thus a control and the subject. However, I believe that most sociologist would agree with me that it SEEMS LIKE that if you grow up in a different country, your expected adult height changes, often by a lot, and even by a few standard deviations.

That would mean that one’s environment and most definitely the local food has a major influence on the kids’s development.

In fact, there is a phenomena seen in the East Asian community where immigrants who came to the Western countries (USA, Canada, Australia) later in life, say in their 20s almost could not get fat or overweight even if they wanted to and ate a lot, but their 2nd generation Asian Canadian (or Asian American) counterpart found themselves struggling with their weight their whole adult lives. At some point in the phase where the teenager turns into an adult, the body’s metabolism changes and the two groups of people who have the same ethnicity starts to diverge in their body shape, both in height and weight.

It seems like the diet that one eats when one is very young and in development dictates one’s adult metabolism level. I suspect that it has to do with the raising of the IGF-1 level in one’s system, and how well one’s body can produce and use insulin.

On average, I would say that above average in height adults in the USA are more likely to be overweight than average in height people and short people. That means that height and weight are positively correlated, pushing one’s BMI steadily higher over time, (since the factor of height is squared and divided over in the BMI Calculation)

What does this all mean?

It seems that the old stereotype of Asians being short may be explained much more by their traditional diet than previously believed. Based on this old World Health Organization report (Click Here for the PDF), it was shown that the growth pattern was almost exactly the same for all tribes and ethnic groups from around the world. That would suggest that if all ethnic tribes were places in the same environment with the same level of healthcare and had the same diet and eating habits, on average, they would have all the same adult height, accounting for the initial length and weight of the person when they were first born. (Multiple studies showed that people who are born big, grow to be bigger, since they start out initially with much more mass, aka many more chondrocytes which had condensated in their embryological development.)

Maybe the Vietnamese are shorter than average because of the lack of dairy products in their diet. I do believe that diet plays a much bigger role than I had thought a year ago. I did show once that eating the shells from a lot of Shellfish, or Shrimp, or Crayfish (Mini Lobsters), or any type of sea life based creature with a keratin/nail like exoskeleton might help in one’s growth pattern. It turns out that Glucosamine Sulphate, which was one of the biggest discoveries and posts on this website (Refer to that viral post here), is derived from the shells of shrimp and shellfish. Yes, technically Glucosamine Sulphate is a compound that is endogenously produced in the human body, but consuming it helps with making many joints in the body increase in thickness and volume, if ever so slightly.

If I was to say one thing about this point, it is that maybe a large factor for the differences in height in the various “races” and ethnic groups is due to their food choices, particularly the lack of dairy products when they were young.

LSJL Update 9-9-2014 Preliminary Measurements of Hand X-rays

Previously, I posted x-rays of my hands.   I loaded with LSJL clamping the three joints of the right index finger.  The two more distal joints I loaded laterally whereas the more proximal joint I loaded overhead ad the other fingers were in the way. I also loaded the two joints of the thumb.  Michael came to the conclusion that the proximal bone had grown but the two more distal bones had not.  My measurements support this conclusion and I’m going to talk about the ramifications of this as well.  If you can please look at the x-ray post and see if you can validate the measurements.

Previously, at times I was clamping twice a day.  I have since gone to once a day as that was not enough time for the soft tissues to recover and the second clamp tended to be effective.  It was nice having a second chance to clamp if I didn’t feel it was effective but the second daily clamp was always worse than the first.  I just try to make each clamp count and if I don’t feel the clamp is effective I start over.

To measure I used the GIMP software tool.  I used grid lines and made my own using the control key at the absolute top and bottom of each bone.   I used the control key to force a straight line.  Doing the lateral view was harder so there may be more measurement error there.

Even though measurements are in inches they are not representative of my actual hand as the x-ray images are not as big as my hand.
Overhead view:
Right distal phalanx-0.53in

Right middle phalanx 0.78in

Right proximal phalanx-1.36in

left distal phalanx-0.52 in

left middle phalanx-0.79 in

left proximal phalanx-1.34in

Lateral View

Right distal phalanx-0.67in

right middle phalanx-1.00in

right proximal phalanx-1.66in

Left distal phalanx-0.67in

left middle phalanx-1.00in

left proximal phalanx-1.61in

Since there is more measurement error with the lateral view.  We’ll rely only on the overhead view.  That’s an increase of 1.5% in finger length.  A commentator named Alex got a lot smaller percentage increase but was not available to follow up.  To give you an idea a 1.5% increase at 72 inches of height gives you an additional inch of height.    I believed that all three bones had grown.  But perhaps it was just the ganglion cysts giving the illusion of growth.

Thumb

Right distal-0.67in

Right proximal-1.06in

Left distal-0.66in

Left proximal-1.10in

Again, only the proximal bone had grown(I loaded the left thumb with LSJL and the right was unloaded).

Why this could be.  Well:

One possibility is that the the joint at the proximal end of the proximal phalanx is more mobile.  For example try pulling your finger like so:

pulling your fingerYou can create quite a lot of separation in the joint.  Same with the wrist which is a part of my arms which have also grown(from about 72.5-74.4″).  I’m not sure what the cause is for the wingspan increase but the mobility of that wrist joint may be a key.

We need to learn more about the properties of these joints and what other joints of the body are of this type.  This is just a theory but it would explain why only the proximal joint has grown.

Evidence that foot length may increase after epiphyseal fusion

If the feet bones can increase in length after epiphyseal fusion perhaps we can use the mechanisms which increase foot length on the long bones.

Gender and age related differences in foot morphology

“Anatomical parameters such as foot length, circumference and height and ankle length, circumference and height were assessed in a sample of males and females divided into three age groups. The groups included young-adult, aged between 20 and 25 years; adult, aged between 35 and 55 years; and old, aged between 65 and 70 years individuals.”

“Comparative analysis of morphometric data between young-adult and adult individuals revealed that the instep length was smaller in adults. The opposite was observed for the great toe and medial foot arch height. Length of ankle was higher in adult than in young-adult individuals, whereas ankle circumference and height were smaller.”<-I don’t know what conclusions to possibly draw from this but there could be something to gather here.

“From a topographic anatomy point of view, foot is in general divided into three parts, namely forefoot, midfoot and hindfoot. The forefoot includes the five toes (phalanges) and the five longer bones (metatarsals). The midfoot represents a pyramid-like association of bones (cuneiform, cuboid and navicular bones) forming the arches of the feet. The hindfoot includes the heel (calcaneus) and the ankle. The heel bone is the largest bone of the foot, whereas the talus bone supports the leg bones (tibia and fibula), forming the ankle”

The elderly is reported to have flatter, longer, and wider feet than younger adults“<-Taken from Age-related differences in foot structure and function.  Although I could not find the information that elderly feet tended to be longer from that study.  They state in regards to this study “Other investigations enlarging their analysis to old people aged 80.2 ± 5.7 years noticed in the elderly group compared with a younger one of the mean age of 20.6 ± 2.6 years flatter, longer, and wider feet than younger adults”

The other citation they use for this is: Foot Health and Shoewear for Women.  And I can’t find anything compelling here other than a statement that a woman’s foot grows larger with age.

“The foot length was measured between the extreme point of heel (foot end) and the extreme point of the longest toe (either first or second toe).”

“The ankle height was considered as the distance between the heel of foot and the line right above the medial malleolus.”

Average foot length of age 35-55 was 269.2 cm and 261.7cm for age 20-25 cm male group.  Foot length was similarly longer for the female middle age versus young adults group.  In males age 65-70 Foot Length was 264.4 cm which is a decrease for middle age but the female group continued to increase in foot length.

So we can’t really conclude that foot length continues to grow with age but this indicates that it may be possible that the feet do grow.

Update 17 – Cartilage Degeneration Disorders – September 1st, 2014

Update 17 – Cartilage Degeneration Disorders – September 1st, 2014

First Issue

In the last month or so I have found out that certain close friends and family members, who are still extremely young, have already started to suffer from severe articular cartilage degeneration. It seems that the phenomena of cartilage degeneration is a much, MUCH more prevalent medical condition than I would have thought.

That is why I am going to put much more focus, effort, and energy on also figuring out how to possibly repair articular cartilage damage than before. I am not saying that I am going to figure out the next best thing to treat osteo-arthritis or tissue inflammation but I understand that what I have been researching non-stop for the last 2 year can be very helpful in my own personal life, and to the people around me who I care about.

This desire to help people become taller and gain height even after skeletal maturity will always be there, with a focus on the scientific research. I also now understand that what I have uncovered can also be used to treat much more severe medical conditions.

If I have the chance to help someone out with a medical condition with the deep insight that I gained from thousands of hours of reading, then I would do that.

Second Issue

Most of the people who have regularly visited the website might have noticed that over time, it has slowly changed in form, and become more technical. Some of it might get harder to understand and read. That is something that I knew would happen. The level of medical understanding needs to improve over time (as well as the quality of writing).

With a much more sophisticated understanding of the overall human body, I would finally be able to understand the research that the world’s top experts are working on. If I can, I want to synthesize the results that they have found to discover something completely new.

A recent search on Google lead me to this question posed in the USMLE Step 1 Exam and it showed me that there is still much more I need to learn and understand before I can ever make a clear and logical argument on our theories before any professional orthopedic specialist.
Embryonic Chondrogenesis

It seems that my understanding of at least the process of Mesenchymal Stem Cell Condensation during embryogenesis to form the Chondrocytes is still lacking on how the protein signal pathways work.

I asked the question later whether the chemical compound Dibutyryl cAMP can be used as a way to get the MSCs in our own blood marrow to go directly into the chondrogenic lineage like they seem to do during the embryogenic process. It would turn out that I was wrong about this issue. Dibutyryl cAMP is a very unique compound which is only expressed/found in chondrocytes. It seems to be a type of chemical indicator used by researchers to check to make sure that what a cell differentiated into is indeed actually chondrocytes.