Me: It would appear that the senescence of growth plates can not just be explained by one triggering step or mechanism like the idea that senescence of growth plates occur only from “growth plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone” or that “senescence might occur because stem-like cells in the resting zone have a finite proliferative capacity, which is exhausted gradually”. I am sure that it is just one of the causes for growth plate eventual failure.

This new article that I have found seems to show the loss of DNA methylation is another main reason. I had found this article more than 2 months ago but at the time I did not understand what it was talking about so I had chosen not to read about it until now when I am more knowledgeable on the minute details on how the growth plates work. They have observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo (within the lab animal). This drop seen in DNA methylation only occurs in the slow proliferation activity of chondrocytes in the resting zone of the animal, but nowhere else  as the rate of DNA methylation stayed the same from the resting zone, to the proliferative layer, to the hypertrophic layer. 

The conclusion reached is that the overall level of DNA methylation decreases during growth plate senescence. It agrees with the idea that (and I quote from the abstract 

“hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism.”

Then the obvious question would be what then causes the loss of DNA methylation? plus the other more practical question, if we can reverse or inhibit the decrease in rate of DNA methylation, can we keep the mechanism for the replication of growth plate chondrocytes in the resting zone constant or even increase in numbers and capacity?

From PubMed website. source link HERE.

J Endocrinol. 2005 Jul;186(1):241-9.

Growth plate senescence is associated with loss of DNA methylation.

This tip is for the regular readers who come to this website. I deeply care about who my regular readers are and I want to try to make this website as user-friendly and intuitive to navigate as possible. This is also why I want to give a tip to the readers of this blog that if you are the type who comes back often to the website hoping to find new article posts, you will probably be disappointed. I don’t spread out the writing of the posts randomly.

This is actually how my schedule really works. Most of the posts that I write comes out during the 12 noon-4 pm time range. I am currently in Seoul, South Korea so for the eastern or pacific time zones in the US, this corresponds to really  8 pm – 12 midnight in the Pacific Time Zone and around  11 pm – 3 am in the Eastern Time Zone. So if you want to be sure the next day’s or the current day’s new posts are out, if you are living in say Los Angeles, that would be at 12 midnight usually. For New York, that would be 3 am.

Of course I am not suggesting that a reader should stay up past 12 or 3 just to wait for the next article posting are out. Get your sleep. My articles and posts appear on a relatively consistent time. So save your time, which I guess is probably 3-5 minutes each day coming back to the website hoping new articles will be posted.

Be smart with your time and allocate this most precious well because it is one of the most important skills one must master as a professional responsible adult. Now have a great day guys!

Me: I wanted to focus this post on the changing form seen in the Japanese female over the last century. If we view the evolution of humans just from the perspective of height, we can guess at a reasonably accurate rate that humans have been getting healthier and living longer than at any other time in human history. From source link HERE

Changes in the physiques of Japanese women,       Much closer to their American sisters    —–     By T W Lim

One of the largest dietary change is probably consumption of milk. Not only has it made Japanese women grow taller, bigger and stronger but the consumption of milk has also advanced the age at which first menstruation happens in Japanese girls from 15 in 1950 to 12 years in 1975.  Only in the US has this record been somewhat matched and surpassed. Girls in the US are reaching puberty,  for example, as early as eight years old according to some reports and puberty is also accelerating though the national average is still about 12. This means that Japanese women have now reached the forefront of first world standards in female puberty. The implications need to be studied more.

In the same time period of 25 years after WWII, Japanese women have also grown more than 4 inches in height. Their weight increased by nearly 10 kg in the same period. Many scientists attribute this growth to the fact that Japanese consumption of dairy products now amounts to more than 50 kg per year, including cheese, milk, butter etc. Percentage of fat has also gone up with the intake of dairy products and that probably explains why Japanese women are now heavier.

American and Japanese researchers have identified over 50 hormones in milk that could possibly explain this phenomenon. The government and private sector has also played a key role in promoting milk,  making it readily available in offices, schools as well as vending machines in railway station. Hormones work in minute amounts and only a small tablespoon (or micrograms) of female hormones like estrogen or progesterone can produced a monumental effect on women’s growth.

Some researchers argue that there is a genetic potential for each race and that the Japanese are reaching their potential through improved diet but this is controversial and not readily proven. This is a controversial theory as it is not known if this so-called genetic potential may become a limiting factor on female growth in Japan. Would it be a genetic limitation such that Japanese women or indeed Asian women will never grow as large as Western women? Will the science of genetics or life sciences or biotechnology or genetically modified food in the future change this genetic potential? All questions remained unanswered.

Yet other researchers have gone beyond milk and look at soy proteins as a source of Japanese growth. These proteins consumed in larger amounts prevent menopausal problems but still promote proteins for growth. This finding is still controversial and it may be safer to say that Japanese are growing taller due to both intake of soy proteins as well as dairy products. There is evidence that even with the increase of soy proteins, there is a corresponding increase in animal proteins to more than 50 grams per day since 40 years ago. Studies have also shown that the soy proteins balance women’s hormones in Japan. These assertions of soy protein theory still need to be studied closely.

More Japanese women are also taking up aerobics, playing recreational sports like golf and strength sports like tennis, increasing their physique and musculature. More are training harder and earlier and Japanese educational sports programs are known to be rigorous and strict. In most other East Asian nations, women cannot afford the leisurely time to play such sports and have less time to exercise than Japanese women, especially in Asian countries which are barely surviving on their food supplies like India, Indonesia which are seeing a large part of their populations starving.

Some in the West wondered how Japanese women who are constrained to small spaces in Japan can grow big and tall suddenly. Wealth has also overcome Japanese space constraints as more and more Japanese women go to ultra-modern gyms and sports clubs to train their muscles. Taut, veined athletic muscles are no longer frowned upon in the Japanese fashion world thanks to fitness trends in the US, a source of Japanese emulation.There are other more minor theories like Japanese moves from sitting on the floor to sitting on chairs, have improved their postures and musculatures accounting for the height and weight increase. Removal of infectious diseases, wealth and better quality of living as well as Japanese infatuation with disinfectant may also be promoting Japanese growth, size and longevity. Other less scientific assertions include more sleep for Japanese improving their metabolism rates. Others have attributed the growth to the many calorie-, vitamins- and minerals-enhanced food and drinks available from vending machines which youngsters drink on their way to night prep schools in place of dinner due to time constraints.

Besides diet, some Japanese researchers and scientists say increase may also be due to Japanese industrial economy producing large amounts of chemical byproducts that are artificially increasing the sizes of women. Dioxins and polystyrenes have been identified by some as chemical substances that may enlarge and extend Japanese female body sizes. They are hormone effectors that have been found in Japanese soil, river and seas. These substances in Japan have been blamed for low sperm counts and making men develop feminine characteristics. Synthetic estrogens have already caused changes in fish and frogs in the rivers.

Finally, some of these changes in Japanese female physique may also be due to Japan’s state intervention. Some schools for example have their kids or encourage their kids to taking vitamins pills in specially prescribed boxes during lunchtime or have arranged volumes of milk or dairy products to promote growth. Others have prescribed rest time to manage youngsters’ metabolic rates. Schools strictly monitor young children’s diet (Weight loss surgery for children) with regular school inspections of what mothers put in their bento or lunch boxes. They regularly prescribe diets with calorie intakes provided for the parents. Parents also have been educated more through the media and during parent-teacher meetings diets are often discussed to standardize growth promoter diet for Japanese children.

Psychological Factors.

Psychologically, Japanese who are afraid that they will stick out because of their height or find it difficult to marry no longer feel like that. Tall women are increasingly envied. In fact, they are so admired that at one time, many Japanese women wear high heel or platform shoes to make themselves look taller, even to the extent of towering over their boyfriends who now have to live with such fashion.

Another psychological factor studied by some social science and psychology researchers in Japan is the growing assertiveness of Japanese women. They are becoming more aggressive and independent compared to their traditional demure image. It is not known if this is due to biological factors. But women are seen as stronger in careers and personalities. Could chemical compounds be responsible for this change?

Me: My collaborator in the project found a very interesting article that shows just how critical the resting zone is in the development of the growth plate itself which I had discovered previously in my searching. I wanted to bring to light the discovery because it shows just which elements in the growth mechanism are the most critical, which must be either preserved or regenerated for longitudinal increase to occur.

Note: As always I am using PubMed and reading just the abstract. The Full Text for the article is either not available or I just didn’t want to expend the energy to do a massive search to find the full article.

1st paper: This article shows just how important the resting zone is to the overall entire growth plate. if you remove the proliferative and hypertrophic zones, apparently adolescent rabbit growth place of the distal ulnar can regrow back in most cases within just 1 week. If you take the growth plates and put them sideways next to the proliferative layer, the chondrocytes in the proliferative layer starts to align themselves in alignment with the resting zone chondrocytes. This also stops the ability of the chondrocytes in the proliferative layer from turning hypertrophic. this suggest the resting zone might have some form of orientation growht factor involved.

2nd paper: This article shows that researchers have been hypothesizing that the real cause of growth plate senescence if because the chondrocytes in the resting zone have a finite proliferative capacity that is gradually depleted. With the rabbits, they saw that the proliferation rate and the chondrocyte density in resting zones decreased with age. Gluccocorticoids and dexamethasone treatment decreased the proliferative rate of the chondrocytes which helped conserve their proliferative capacity for later. They slowed the senescence of growth plates and slowed the depletion of the number of chondrocytes in the resting zone. They also foun that estradiol cypionate treatment slowed resting zone chondrocyte proliferation

The Implications (READ THIS!): The first article shows how important the resting zone is to the overall growth plate. As long as you have the resting zone, you can create all of the rest of layers. The 2nd article make me understand at a still superficial level that apparently the puberty we go through is just estrogen telling the resting zone chondorcytes to proliferate faster, which means rate of loss>rate of growth. as long as that happens, the proliferation and subsequent hypertrophy and apoptosis is the explanation behind the jump in rate of growth or height increase we see in kids going through puberty and the growth spurts. However, the growth spurts do come at a cost, especially the growth spurt associated with puberty. The estrogen has pushed the rate of loss over a limit where the rate of growth is not enough to stave off the loss of the number of chondrocytes seen in the resting zone.

If we remember the cases seen of the 3 men who had mutations in their estrogen receptors, we remember that for 2 of the men, they still had open growth plates with cartilage even in their 30s. This shows that as long as estrogen doesn’t come along to accelerate the rate of decrease in the number of chondrocytes in the resitng zone, the rate of proliferation thus rate of increase of chondrocytes in the resting zone is probably (and i am making a big leap of faith here) self-sustaining, which will not ever drop the number of chondrocytes around. What we could do then to create growth spurts but never loss all of the chondrocytes is to create a way to inhibit and promote estrogen release alternatively where the loss of chondrocytes can be made up for by inhibiting estrogen affects afterwards. 

A device can be build that can specifically block estrogen ligands from reaching their receptors on the growth plate in a pulsing, sinusoidal fashion to use the feedback mechanism of the two rates themselves to cause multiple growth spurts throughout an adolescent’s growth and development!

source link HERE. and from source link 2 HERE. both are PubMed Articles.

Endocrinology. 2002 May;143(5):1851-7.

The role of the resting zone in growth plate chondrogenesis.

J Endocrinol. 2006 Apr;189(1):27-36.

Depletion of resting zone chondrocytes during growth plate senescence.

I have been very patient with the numerous numbers of grow taller scams and bullshit on the internet but I have recently been loosing the tolerance for these types of sites.

When I was first starting out on the website, I had to accept the idea that the internet which is a sort of Wild West where almost anything goes and swindlers and sales people try to sell everything under the sun to get people like us to open our wallets and pull out our credit cards. I accepted it and I was sort of happy that I would be able to build a sort of brand and place where real height increase and grow taller research and information could be found. One of the first things I did on the website was to create a section which lists all of the fake, non useful, sleazy websites and webpages out there who are trying to trick me. I worked on it for 3-4 days finding nearly a hundred websites. I went through as many google ranking webpages as possible to find all of the fake stuff.

Most of it were affiliate websites and links to the scam Grow Taller 4 Idiots or the (Company will not be named) program. There were a lot of grow taller supplements out there too which made me realize that most people wanted a easy solution to their problem which doesn’t exist. I slowly wrote out the product reviews trying to make the internet a better place and blasted all of the grow taller supplements showing how none of them work.

However, now I am tired. I am very tired of the crap I am finding on the internet. The frustration has been building and I don’t know how much I can take. It is becoming harder and harder to find real useful information for the website since the fake grow taller websites have been using all the SEO and internet marketing tricks to rank higher on Google than the useful website which must be out there. If I type in the phrases “height increase” or “grow taller” I don’t see my website on the front  page, or any of the resulting pages. My website is ranked somewhere in the lower end and for any of the genuine people who want to grow taller, they never find my website. It is a loss/loss situation for everyone, except maybe the people who are plugging the Grow Taller 4 Idiots programs.

I want to beat and eliminate all of the webpages that do nothing but make my life and the research 10X harder than it already is. Why can’t Google realize that for this specific niche on the internet, nearly 95% of all of the website are just fake sales pages which do nothing but annoy people and give no real value? They should be trying to remove those websites and stop all the people playing the internet marketing game in backlinking.

How many times do I have to read a fake sales page tell me that I should drink milk, get more sleep, and do some stretching? I am dealing with bullshit after bullshit everyday in searching through the internet space. I want to be ranked higher, get more traffic, and help more people. I want to be at least on the 1st page of google rankings when a person types in the phrase “how do i grow taller” at least.

I had previously wrote about the invention using Guanyl Cyclase through a vector injection in gene therapy to increase in height apparently twice HERE and HERE. Tyler in a post on June 18 this year wrote about the exact same thing HERE. That was more than a month before I started on this website.

It is quite clear that we have been scouring through the internet to try to find everything under the sun to push this endeavor and search for a possible noninvasive way to increase the height of people who have already reach physical maturity. So far I would say that we are doing a rather good job and at this rate, we probably could cover everything that is on the internet. One day we will have to regularly contact real doctors, specialists, and surgeons to be able to get answers.

So the question I wanted to answer in this post is why is guanyl cyclase and natriuretic peptides important for possible height increase and growing taller. I’ll just assume that you know the basics of the growth process with knowledge on the hormones and growth plate function.

You have these peptides known as natriuretic peptides which are ligands. There is 3 types in a specific family. You have the ANP aka atrial natriuretic peptide , the brain natriuretic peptide aka BNP, and the C-type natriuretic peptide aka CNP. The effect of the types of natriuretic peptides of ANP and CNP which are ligands for the receptors GC-A and GC-B. When the 3 types of ligands were tested on a culture of mice tibias simulating the longitudinal growth process in bones. It showed that CNP produced more cGMP than ANP which resulted in longer bones. closer look at the cells showed an increase in the height of the proliferative and hypertropic layers in the mouse tibias with CNP.   To mimic the binding of the CNP and GC-B, the experimenters used similar compounds. The conclusion of the study showed that the CNP/GC-B pathway is very significant in the endochondral ossification process.

Let’s look at this specific article found from PubMed. Source Link HERE.

J Biol Chem. 1998 May 8;273(19):11695-700.

Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.