Monthly Archives: September 2012

What Proteins And Genes Are Good Targets For Height Growth? (Tyler Guest Post)

[Me: I have been in contact with Tyler of HeightQuest.Com for almost since the beginning and I have hoped that he could write a guest post for the website to speak about what he has found in his quest for height. Finally he managed to write something for all of us. This is his guest post. I have read it and I feel that this post is a very critical piece in understanding the genetics of growth and height. I wanted to thank Tyler again for his contributions.]

I have a done a lot of analysis on what genes are best for height growth. And there are several genes that are better targets than others.

Estrogen and it’s receptors are highly inefficient targets even though they are involved in height growth. Estrogen receptors have different effects based on differentiation stage and in gender. ERalpha, ERbeta, and GPR30 are the estrogen receptors typically identified with growth. And although GPR30 seems to be the most promising estrogen receptor height increase knockout targets, ERalpha and ERbeta have mixed effects in studies with knockout sometimes increasing and other times decreasing height. There are mutations with estrogen receptors in overgrowth but they are specific receptors.

p-ERK1 phosphorylation and formation of AP-1 complex is another gene target with mixed height increase results. Sometimes ERK1 phosphorylation stimulates chondrogenesis and other times it inhibits. Same with AP-1. Thus even though both ERK1 and AP-1 are important to height growth the conflicting results makes them poor targets.

GH is another poor target. Although IGF-1 is a good target for height growth, based on transgenic models of IGF-1 showing overgrowth, and it is downstream target of GH, GH is a poor target to try to increase via supplements or other methods to induce overexpression. Several HGH studies have shown no overgrowth and other GH related proteins like Ghrelin and GHRP showed no overgrowth when overexpressed. SOCS2 which is a GH inhibitor causes overgrowth when inhibited and we know GH is important to height growth. However, there are likely negative feedback mechanisms, likely SOCS2, that make GH overexpression not cause overgrowth. There are several studies that associate GH with Gigantism however most of those studies are based purely on phenotype and do not fully quantify what’s going on in the body. The tumor in all likelihood is doing things other than causing GH overexpression.

IGF2 is a very promising height increase target. IGF2 transgenic species show overgrowth. Reduction of IGF2R which reduces free IGF2 causes overgrowth. A specific mutation in H19 which seems to reduce free IGF2 also increases height. PLAG1 which increases IGF2 levels also causes overgrowth. The target of IGF2 and IGF1 is increasing Akt. LSJL increases Akt phosphorylation according to Knee Loading Stimulates Bone Formation in Tail-Suspended Mouse Hindlimb. Loads in this study were 1N at 5Hz for 5min. Same was taken 5 days after initiation of LSJL. One day after loading. Akt1 and phosphorylation of Akt1 is also associated with overgrowth.

CNP is also uniformly associated with height increase. Knockout of the CNP inhibitor FGFR3 increases height. Knockout of the CNP decoy receptor NPR3 and upregulation of the CNP actual receptor NPR2 also increases height. CNP and it’s regulators are very promising targets for height increase.

The SHOX genes are another great target with knockout causing short stature and transgenic overexpression causing tall stature.

HMGA2 and it’s regulators are another strong series of genes associated with overgrowth. LSJL upregulates several genes including HMGA2 and Lin28b which downregulates the HMGA2 inhibitor let-7.

Note that these targets will only work with active growth plates. The most likely reason that you can grow taller with chondrocytes and not osteogenic cells is that cartilage can grow interstitially(growth from within) wheres osteogenic cells typically don’t. Thus you need to induce chondrogenesis in the bone to grow taller if you don’t have active plates(LSJL upregulates the three major chondroinductive genes at significant levels Sox9, Aggrecan, and COL2A1). There are several cases of non-invasive/non-tumor ectopic chondrogenesis in the bone but many seem to be in children and I haven’t found any associated with overgrowth. Too bad scientists won’t just induce ectopic chondrogenesis in an adult animal bone to see if it makes the bone grow longer.

But why are you focused on Estrogen and HGH when SOCS2, IGF2, SHOX, CNP, and HMGA2 are much better targets. HGH is a much less harmful target as overexpression has never caused reduced growth. However, knockout of estrogen and receptors have caused reduced growth which makes it a poor target for reduction with aromatase inhibitors. Other genes have much more linear effects and are much better targets.

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature.
“We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways and fundamental cellular processes, followed by chromosomal aberrations including copy number variants and imprinting disorders associated with short stature. Many novel causes of growth hormone (GH) deficiency as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GH deficiency are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3 and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFκB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in approximately 3% of short children, and also rasopathies (e.g. Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, copy number variants and imprinting disorders.”

“IGF-II not only is a mediator of intrauterine development but also contributes to postnatal growth “

Taller People Are More Likely To Develop Cancer

About a year ago (2011) there was a study that was published and spread by the international news groups about the link between the increased height of the general world population and the increase in cancer rates in the world.

I remember once a person on a website saying that technically, cancer is just any type of cell division growth that becomes uncontrollable. The cells can not stop differentiating and multiplying and move from a benign tumor to a malignant tumor. Thus, taller people usually have more mass than shorter people. So they have more cells. That would correlate in a linear way to the fact that with more mass and more cells, there is a higher chance that one of the cells in the taller person’s body will turn malignant and start multiplying without stop.

Of course there are some factors which can increase the possibility go cell mutation into uncontrollable growth, like radiation, electricity, certain chemicals, and even virus. There are also factors which decrease the possibility of cancer like exercise, resveratrol, good food, etc. However, what the guy was making the point was that on average, taller people should have a higher rate of possible cancer, if all other factors are held constant.

I will only post on here the story told by The Telegraph, a news site from the UK (link at the bottom) and the Huffington Post (source HERE). If you wanted to read more about the studies and the news articles published talking about it, refer to the links I have put up at the bottom of the article. As always, the most important parts will be highlighted. Thank you.

Tall people at greater cancer risk

Taller people are more likely to get cancer, a study shows.

7:00AM BST 21 Jul 2011
The likelihood of developing the disease rises 16 per cent for every extra four inches in height among women – and a similar pattern is also seen in men.

Although previous research has linked height with particular tumours – such as breast in women and testicular in men – new findings show the phenomenon is not restricted to any types of the disease.

Dr Jane Green, who led the research, said: “The fact that the link between height and cancer risk seems to be common to many different types of cancer in different people suggests there may be a basic common mechanism, perhaps acting early in peoples’ lives, when they are growing.

“Of course people cannot change their height. And being taller has actually been linked to a lower risk of other conditions, such as heart disease.”

Hormone levels related to childhood growth, and in turn to cancer risk in later life, could be behind the phenomenon.

It was also suggested the link could simply be down to the fact that taller people have more cells in their bodies, and so a greater chance of developing cancerous cell changes.

Dr Green said: “One possible reason is fairly obvious – tall people have more cells so there is a greater chance that one of them could mutate.

“But being tall is also related to hormonal growth factors which leads to a higher turnover of cells and this is an interesting possibility.

“There is nothing we can do about our height but these findings may open the door to discovering how some cancers may develop.”

She went on: “Although we carried out our study in women when we compared the results to previous ones involving both sexes we found a similar link between cancer and height in men.

“So there is no gender bias and the association seems to apply to a range of cancers – it’s just most studies have been carried out on the more common ones like breast and colorectal.”

Dr Green and colleagues, whose findings are published online in The Lancet Oncology, said previous studies have shown a link between height and cancer risk but their’s extends the findings to more cancers and for women with differing lifestyles and economic backgrounds.

The results also suggest increases in the height of populations over the course of the 20th century might explain some of the changes in cancer incidence over time.

The height of European adults increased by about 1cm (0.39 inches) per decade during the twentieth century, and the study suggests that this may explain around 10-15 per cent of the rise in cancer cases seen over this period.

The researchers assessed the association between height and cancer among 97,000 cases identified from the Million Women Study which included 1.3 million middle-aged women in the UK enrolled between 1996 and 2001.

During an average follow-up time of about ten years the largest study of its kind found the risk rose in tandem with height and included at least ten types of the disease including breast, skin, bowel, leukaemia and ovarian – a wider range than initially thought.

The researchers who looked at women with heights ranging from under 155cm (5ft 1in) to 175cm (5ft 9in) and taller then compared their results with those from ten previous studies involving both men and women and found they were strikingly similar.

Dr Green said: “We showed the link between greater height and increased total cancer risk is similar across many different populations from Asia, Australasia, Europe, and North America.”

Dr Andrew Renehan, of Manchester University, who reviewed the study for the journal, said: “In the future, researchers need to explore the predictive capacities of direct measures of nutrition, psychosocial stress and illness during childhood, rather than final adult height.”

Sara Hiom, director of health information at Cancer Research UK, said: “Tall people need not be alarmed by these results.

“Most people are not a lot taller (or shorter) than average, and their height will only have a small effect on their individual cancer risk.

“This study confirms the link between height and cancer paving the way for studies to help us understand why this is so.

“On average, people in the UK have a more than one in three chance of developing cancer in their lifetime. So it’s important that everyone is aware of what is normal for their body and go see their doctor as quickly as possible if they notice any unusual changes.

“And while we can’t control our height, there are many lifestyle choices people can make that we know have a greater impact on reducing the risk of cancer such as not smoking, moderating alcohol, keeping a healthy weight and being physically active.”

Tall Women May Have A Greater Cancer Risk

Huffington Post   Amanda Chan First Posted: 07/21/11 02:28 PM ET Updated: 09/20/11 06:12 AM ET

Tall women may be more likely to develop several different cancers than their shorter counterparts, a new study suggests.

Published in the journal Lancet Oncology, the study shows that for every 4-inch increase in height, the risk of 10 different cancers — include leukemia, melanoma, breast, ovarian, bowel and uterine cancer — goes up 16 percent.

“Because height is linked to a wide range of cancersin a wide range of people, [the finding] may give us a clue to basic common mechanisms for cancer,” study researcher Jane Green, a cancer epidemiologist at the University of Oxford, told ABC News.

So what should you do if you’re tall? First, don’t panic. The study found an association, not direct link. And of course, height is something that is largely out of our control — affected by genetics and nutrition.

The results also don’t suggest that tall people need extra cancer screening.

Luckily, it’s not all bad news for tall people — a study published this month in the Journal of Epidemiology and Community Health shows that longer legs seems to be tied with a longer lifespan, the Daily Mailreported.

This isn’t the first study to link physical attributes to cancer risk. Research published last year in the British Journal of Cancer showed that men who have long index fingers have a decreased risk of prostate cancer, because finger length seems to be linked with the amount of testosterone a man produces.

In the new study, the researchers analyzed the health information and height of more than 1 million women who participated in the Million Women Study between 1996 and 2001, none of whom had been diagnosed with cancer at the start of the study. They followed the women for nine years.

The researchers grouped the women into groups by height, with the shortest group consisting of women who are less than 5 feet 1 inch in height, and the tallest group consisting of women who are 5 feet 9 inches or taller.

Even though the researchers found that the taller women seemed to have fewer children and drink more alcohol than the shorter women, they were less likely to be smokers or obese and were more likely to be wealthy and active, the study said. Despite this, the taller women seemed to be more likely to develop cancer.

For every 4 inches of height, cancer risk increased by 32 percent for skin cancer, 29 percent for kidney cancer, 26 percent for leukemia and 16 percent for breast cancer.

The Telegraph UK – ScienceShot – The Guardian UK – Time Healthland – BBC News

The Connection Between Height And Fibroblast Growth Factor FGF

[Note: This is the 3rd guest post by the coworker who has been contributing in writing posts for the website. The previous they wrote about was on statin HERE and bone morphogenic proteins BMPs HERE,  Thanks Nicki.]

FGFs

Fibroblast growth factors (FGFs) and their receptors (FGFRs) negatively regulate longitudinal bone growth. Activating FGFR3 mutations impair growth, causing human skeletal dysplasias, whereas inactivating mutations stimulate growth. Systemic administration of FGF-2 to mice stimulates bone growth at low doses but inhibits growth at high doses. In organ culture, FGF-2 inhibits growth by decreasing growth plate chondrocyte proliferation, hypertrophy and cartilage matrix synthesis. Local FGF-2 infusion accelerates ossification of growth plate cartilage. Thus, FGFs may regulate both growth plate chondrogenesis and ossification.

Fibroblast growth factor (FGF) signaling is essential for endochondral bone formation. Most previous work in this area has focused on embryonic chondrogenesis. To explore the role of FGF signaling in the postnatal growth plate, we quantitated expression of FGFs and FGF receptors (FGFRs) and examined both their spatial and temporal regulation.

Toward this aim, rat proximal tibial growth plates and surrounding tissues were microdissected, and specific mRNAs were quantitated by real-time RT-PCR. To assess the FGF system without bias, we first screened for expression of all known FGFs and major FGFR isoforms. Perichondrium expressed FGFs 1, 2, 6, 7, 9, and 18 and, at lower levels, FGFs 21 and 22. Growth plate expressed FGFs 2, 7, 18, and 22. Perichondrial expression was generally greater than growth plate expression, supporting the concept that perichondrial FGFs regulate growth plate chondrogenesis. Nevertheless, FGFs synthesized by growth plate chondrocytes may be physiologically important because of their proximity to target receptors. In growth plate, we found expression of FGFRs 1, 2, and 3, primarily, but not exclusively, the c isoforms. FGFRs 1 and 3, thought to negatively regulate chondrogenesis, were expressed at greater levels and at later stages of chondrocyte differentiation, with FGFR1 upregulated in the hypertrophic zone and FGFR3 upregulated in both proliferative and hypertrophic zones. In contrast, FGFRs 2 and 4, putative positive regulators, were expressed at earlier stages of differentiation, with FGFR2 upregulated in the resting zone and FGFR4 in the resting and proliferative zones. FGFRL1, a presumed decoy receptor, was expressed in the resting zone.

With increasing age and decreasing growth velocity, FGFR2 and 4 expression was downregulated in proliferative zone. Perichondrial FGF1, FGF7, FGF18, and FGF22 were upregulated.

In summary, we have analyzed the expression of all known FGFs and FGFRs in the postnatal growth plate using a method that is quantitative and highly sensitive. This approach identified ligands and receptors not previously known to be expressed in growth plate and revealed a complex pattern of spatial regulation of FGFs and FGFRs in the different zones of the growth plate. We also found temporal changes in FGF and FGFR expression which may contribute to growth plate senescence and thus help determine the size of the adult skeleton.

The family of FGFs constitutes at least 22 members that interact with at least four receptors (FGFR) and are major regulators of embryonic bone development.Both FGF1 and -2 as well as FGFR1, -2, and -3 are expressed in chondrocytes.In humans, activating mutations in the FGFR3 cause achondroplasia,the most common type of human dwarfism (97% of mutations have a Gly to Arg mutation in codon 380).Other forms of chondrodysplasia due to mutations in the FGFR3 gene include hypochondroplasia, a milder form of dwarfism and two severe types, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and thanatophoric dysplasia.Conversely, mice with an inactivating mutation in the FGFR3 gene demonstrate increased longitudinal growth. In addition, overexpression of FGF2 slows longitudinal growth.Only very recently, mice lacking FGF18 have been generated. These mice demonstrated a phenotype similar to that observed in mice lacking FGFR3, including expanded proliferating and hypertrophic zones, increased proliferation, differentiation, and Ihh signaling.In addition, FGF18 deficiency leads to delayed ossification and decreased expression of osteogenic markers, not seen in the FGFR3 knockout phenotype, which prompted the authors to suggest that FGF18 coordinates chondrogenesis and osteogenesis through FGFR3 and -2, respectively. In addition, FGF18 appeared to act as a physiological ligand for FGFR3 in the growth plate. These studies indicate that FGFR signaling reduces growth by inhibiting proliferation and differentiation.

Mancilla et al.  studied the effects of FGF2 on chondrocyte differentiation in a metatarsal organ culture system and found three growth-inhibiting mechanisms for FGF2: decreased growth plate chondrocyte proliferation, decreased cellular hypertrophy, and at high concentrations, decreased synthesis of cartilage matrix. Recently, a mouse model for thanatophoric dysplasia characterized by severe dwarfism was used to study the relationship between FGF signaling and the Ihh/PTHrP feedback loop. In these newborn mice with an activated FGFR3, Ihh and PTHrP mRNA expression were both down-regulated. In the same study, embryonic metatarsals from wild-type mice were cultured in the presence of FGF2, and similar results were found. Interestingly, FGF inhibited chondrocyte proliferation by down-regulating Ihh expression. Moreover, FGF and PTHrP signals independently inhibited chondrocyte differentiation. It was concluded that FGFR3 and PTHrP/Ihh signals act through two integrated parallel pathways that mediate both overlapping and distinct functions during longitudinal bone growth. In a recent study by Minina et al. , using a limb culture system, it was found that FGF and BMP signaling are antagonistic in the regulation of chondrocyte proliferation and in Ihh expression and the process of hypertrophic differentiation. The balance between the two adjusts the pace of the differentiation process to the proliferation rate.

Abstract

In vivo, fibroblast growth factor-2 (FGF-2) inhibits longitudinal bone growth. Similarly, activating FGF receptor 3 mutations impair growth in achondroplasia and thanatophoric dysplasia. To investigate the underlying mechanisms, we chose a fetal rat metatarsal organ culture system that would maintain growth plate histological architecture. Addition of FGF-2 to the serum-free medium inhibited longitudinal growth. We next assessed each major component of longitudinal growth: proliferation, cellular hypertrophy, and cartilage matrix synthesis. Surprisingly, FGF-2 stimulated proliferation, as assessed by [3H]thymidine incorporation. However, autoradiographic studies demonstrated that this increased proliferation occurred only in the perichondrium, whereas decreased labeling was seen in the proliferative and epiphyseal chondrocytes. FGF-2 also caused a marked decrease in the number of hypertrophic chondrocytes. To assess cartilage matrix synthesis, we measured 35SO4 incorporation into newly synthesized glycosaminoglycans. Low concentrations (10 ng/ml) of FGF-2 stimulated cartilage matrix production, but high concentrations (1000 ng/ml) inhibited matrix production. We conclude that FGF-2 inhibits longitudinal bone growth by three mechanisms: decreased growth plate chondrocyte proliferation, decreased cellular hypertrophy, and, at high concentrations, decreased cartilage matrix production. These effects may explain the impaired growth seen in patients with achondroplasia and related skeletal dysplasias.

Abstract

FGF21

Fibroblast Growth Factor 21 (FGF21) modulates glucose and lipid metabolism during fasting. In addition, previous evidence indicates that increased expression of FGF21 during chronic food restriction is associated with reduced bone growth and Growth Hormone (GH) insensitivity. In light of the inhibitory effects on growth plate chondrogenesis mediated by other FGFs, we hypothesized that FGF21 causes growth inhibition by acting directly at the long bones′ growth plate. We first demonstrated the expression of FGF21, FGFR1 and FGFR3 (two receptors known to be activated by FGF21), and β-klotho (a co-receptor required for the FGF21-mediated receptor binding and activation) in fetal and 3-week old mouse growth plate chondrocytes. We then cultured mouse growth plate chondrocytes in the presence of graded concentrations of rhFGF21 (0.01-10 μg/ml). Higher concentrations of FGF21 (5 and 10 μg/ml) inhibited chondrocyte thymidine incorporation and collagen X mRNA expression. 10 ng/ml GH stimulated chondrocyte thymidine incorporation and collagen X mRNA expression, with both effects being prevented by the addition in the culture medium of FGF21 in a concentration-dependent manner. In addition, FGF21 reduced GH binding in cultured chondrocytes. In cells transfected with FGFR1 siRNA or ERK 1 siRNA, the antagonistic effects of FGF21 on GH action were all prevented, supporting a specific effect of this growth factor in chondrocytes. Our findings suggest that increased expression of FGF21 during food restriction causes growth attenuation by antagonizing the GH stimulatory effects on chondrogenesis directly at the growth plate. In addition, high concentrations of FGF21 may directly suppress growth plate chondrocyte proliferation and differentiation.

Abstract

Endochondral ossification is a major mode of bone formation that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growth is accompanied by expansion of proliferating and hypertrophic chondrocytes within the cartilaginous growth plate. Thus, FGFR-3 appears to regulate endochondral ossification by an essentially negative mechanism, limiting rather than promoting osteogenesis. In light of these mouse results, certain human disorders, such as achondroplasia, can be interpreted as gain-of-function mutations that activate the fundamentally negative growth control exerted by the FGFR-3 kinase.

Conclusion: It appears that the Fibroblast Growth Factors, The FGF 1,2,3,4 all regulate the endochondral ossification process. There are a few studies that showed low rates of the FGF seems to increase longitudinal growth of the growth plates on the perineum outer layer but at high levels, all of the FGFs seems to inhibit the bone lengthening and slow down the growth process. As stated above

“”We conclude that FGF-2 inhibits longitudinal bone growth by three mechanisms: decreased growth plate chondrocyte proliferation, decreased cellular hypertrophy, and, at high concentrations, decreased cartilage matrix production””

The mechanism that is guessed to inhibit it is by down-regulating Ihh expression. The FGF21 does the same thing.

Increase Height And Grow Taller Using Nitric Oxide

Another compound that I have seen a lot of talk on the Impartial Height Increase Boards was the talk of either trying to increase the release of Nitric Oxide into the system. Here is what I found on the compound.

From source link HERE

Me: It turns out Nitric Oxide is derived from the amino acid Arginine. The production of Nitric Oxide occurs when the amino acid L-arginine is converted into L-citruline through an enzyme group known as Nitric Oxide Synthase (NOS). Apparently you can increase the release of NO in the system by either exercising, takin orally amino acid supplements, and such. Interestingly, in my searching it seems HeightQuest also wrote a post suggesting that NO might possibly be used to increase height located HERE. Tyler states that NO seems to be able to only lengthen the flat, irregular, and short bones but not the long bones since NO seems to only affects to osteoblasts (at least claimed by him). I would that since the effect of NO is basically to relax the body and make blood vessels increase in diameter, leading to better cell communication, it can only help in any type of cellular mechanisms.

From the website Nutrition Express…

What is nitric oxide and how does it work?

by Jason Clark, BSc, MSc
What Is nitric oxide and how does it work?
Some people think it’s the gas that makes us laugh at the dentist office. Some think it’s the fuel racecar drivers use to speed up their cars. But it’s neither. Nitric oxide is a molecule that our body produces to help its 50 trillion cells communicate with each other by transmitting signals throughout the entire body.

Nitric oxide has been shown to be important in the following cellular activities:

• help memory and behavior by transmitting information between nerve cells in the brain
• assist the immune system at fighting off bacteria and defending against tumors
• regulate blood pressure by dilating arteries
• reduce inflammation
• improve sleep quality
• increase your recognition of sense (i.e. smell)
• increase endurance and strength
• assist in gastric motilityThere have been over 60,000 studies done on nitric oxide in the last 20 years and in 1998, The Nobel Prize for Medicine was given to three scientists that discovered the signaling role of nitric oxide.

Nitric oxide and heart disease 
Nitric oxide has gotten the most attention due to its cardiovascular benefits. Alfred Nobel, the founder of the Nobel Prize, was prescribed nitroglycerin over 100 years ago by his doctor to help with his heart problems. He was skeptical, knowing nitroglycerin was used in dynamite, but this chemical helped with his heart condition. Little did he know nitroglycerin acts by releasing nitric oxide which relaxes narrowed blood vessels, increasing oxygen and blood flow.

The interior surface (endothelium) of your arteries produce nitric oxide. When plaque builds up in your arteries, called atherosclerosis, you reduce your capacity to produce nitric oxide, which is why physicians prescribe nitroglycerin for heart and stroke patients.

Nitric oxide and erectile dysfunction 

Viagra and other impotence medications work due to their action on nitric oxide. One cause of impotence is unhealthy and aged arteries that feed blood to the sexual organs. Viagra works by creating more nitric oxide, causing a cascade of enzymatic reactions magnifying and extending nitric oxide, causing more blood flow and better erections.

How to increase nitric oxide in your body 

The most common way to increase nitric oxide is through exercise. When you run or lift weights, your muscles need more oxygen which is supplied by the blood. As the heart pumps with more pressure to supply the muscles with blood, the lining in your arteries releases nitric oxide into the blood, which relaxes and widens the vessel wall, allowing for more blood to pass though. As we age, our blood vessels and nitric oxide system become less efficient due to free radical damage, inactivity, and poor diet, causing our veins and arteries to deteriorate. Think of a fire hose as water rushes through it to put out a fire – it needs to expand enough to handle the pressure, still keeping enough force to put out the fire. Athletes and youth have the most optimal nitric oxide systems, reflecting their energy and resilience.

Diagram 1Another way to increase nitric oxide is through diet, most notably by consuming the amino acids L-arginine and L-citrulline. Arginine, which can be found in nuts, fruits, meats and dairy, directly creates nitric oxide and citrulline inside the cell (diagram 1).(6) Citrulline is then recycled back into arginine, making even more nitric oxide. Enzymes that convert arginine to citrulline, and citrulline to arginine need to function optimally for efficient nitric oxide production. We can protect those enzymes and nitric oxide by consuming healthy foods and antioxidants, like fruit, garlic, soy, vitamins C and E, Co-Q10, and alpha lipoic acid, allowing you to produce more nitric oxide. Nitric oxide only lasts a few seconds in the body, so the more antioxidant protection we provide, the more stable it will be and the longer it will last. Doctors are utilizing this science by coating stents (mesh tubes that prop open arteries after surgery) with drugs that produce nitric oxide.

Nitric oxide for athletes and bodybuilders 
Increasing nitric oxide has become the new secret weapon for athletes and bodybuilders. Athletes are now taking supplements with L-arginine and L-citrulline to increase the flow of blood and oxygen to the skeletal muscle which can augment strength and endurance. They also use them to facilitate the removal of exercise-induced lactic acid build-up which reduces fatigue and recovery time. Since arginine levels become depleted during exercise, the entire arginine-nitric oxide – citrulline loop can lose efficiency, causing less-than-ideal nitric oxide levels and higher lactate levels. Supplements can help restore this loop allowing for better workouts and faster recovery from workouts.With nitric oxide deficiencies due to aging, inactivity, smoking, high cholesterol, fatty diets, and lack of healthy foods, increasing your nitric oxide levels can help increase your energy, vitality and overall wellness. The basic adage of eating well and staying active all makes sense now.

WARNING: If you have an existing heart condition or abnormal blood pressure, please consult your healthcare professional before taking supplements to increase nitric oxide levels.

The Bone Growth Pill From Zymogenetics

More than a decade ago the biotech company Zymogenetics located in Seattle had apparently found 3 types of compounds (2 synthetic, and 1 natural) which had shown that they can stimulate osteoblasts, such as parathyroid hormone and bone morphogenic proteins (BMPs). After some research, I discovered the natural compound was statin, the compound most commonly known for being in the Lipitor drug used to lower cholesterol. My coworker had actually written her first post on the possibility of using Statin to possibly increase height and grow taller.

If you really wanted to know what the other two synthetic compounds are, then click on the links below which are old patents that have passed their time limit

Patent Link 1 (# 7951380) – Title: “Methods of stimulating bone growth using ZVEGF4 polypeptides” –

Patent Link 2(# AU1998057981) – Title: “COMPOSITIONS AND METHODS FOR STIMULATING BONE GROWTH”

The drugs that they were testing never got any more news about what happened to them. From working in the past in the pharmaceutical industry, I would guess there was not enough funding or interest in getting the drugs out to market. It was indeed an absolute breakthrough for the medical community and especially for people suffering from osteoporosis.

The thing to note that the drug was never intended to be used to extend the actual form in our bodies, but to increase the body density in our bones. So technically, the drugs indeed did promote bone growth, but did not grow bones in the way us height increasers had been hoping for.

The article I will be posting below is from the Science Daily website HERE. Note that it was written in 1999, such a long time ago. Another article written by the BBC is located HERE.

New Chemicals Could Lead To First Bone Growth Pill

ScienceDaily (Mar. 22, 1999) — ANAHEIM, Calif., March 21 — New chemicals that, if successful, could become the first osteoporosis treatment to stimulate new bone growth — rather than merely retard bone loss — were described here today at a national meeting of the American Chemical Society, the world’s largest scientific society. Researchers from the Seattle biotechnology company ZymoGenetics Incorporated said their new compounds are showing positive results in animals and, unlike other bone-growth candidates, can be put in a pill.

In humans, bone undergoes continuous remodeling, with cells called osteoclasts “eating up”old bone as osteoblast cells replace it with new bone. Osteoporosis, which affects some 15-20 million Americans, is caused by increased bone breakdown without new bone formation. The result is a loss of bone mass and increased susceptibility to fractures, most commonly in those age 45 and older. The cost of treatments associated with osteoporosis in the U.S. has been estimated at $3.8 billion annually.

Current treatments, including estrogens, all act to decrease bone loss. They can’t do anything about bone that is already gone and, therefore, are not helpful to everyone. “Our new bone forming agents may have better and more widespread utility for treatment of osteoporosis,” said ZymoGenetics senior scientist Nand Baindur, Ph.D.

There are currently no drugs available to help grow bone. Researchers have tried giving patients proteins that the body naturally uses to stimulate osteoblasts, such as parathyroid hormone and bone morphogenic proteins (BMPs). But, according to Dr. Baindur, those clinical trials have been mostly unsuccessful or inconclusive. Furthermore, he explains that proteins are big molecules which can usually be given only by injection and don’t hold up well in the body. Even if such treatments worked, he adds, the proteins are generally difficult to formulate and manufacture, tending to eventually make them expensive.

Instead of using the proteins themselves, Dr. Baindur’s laboratory screened tens of thousands of compounds for the ability to stimulate BMPs. They have selected three — two synthetic chemicals and one natural product — for pre-clinical development, and early indications look promising. “This is the first report of small molecule drug-like compounds which have been shown to stimulate the formation of new bone in animals,” says Dr. Baindur.

Such small molecule compounds are not only relatively inexpensive and easily made, but usually quite stable. Dr. Baindur adds that they can also be easily modified or formulated as the need arises. The new compounds should be able to be put into pill form. While no human tests have yet been conducted, Dr. Baindur says “these compounds are predicted to be useful in the clinical treatment of osteoporosis and related bone-deficit conditions, including bone fractures. As bone formation agents, they can potentially be given alone or in combination with agents which decrease bone loss.”

While bone regenerating pills are probably years away from the market, there is the possibility that one of the new compounds might have a head start in clinical trials. The natural product candidate is part of a chemical class called statins, some of which are already in use for the treatment of heart disease.

 

A Study On Diastrophic Dysplasia

This post is added for information reasons so the reader and I will be more aware of the types of dwarfism conditions. Diatrophic dysplasia is one of those types of dwarfism that usually results in severe types of dwarfism because the limbs are also affected and become stunted.

From the National Institute of Health government website HERE

What is diastrophic dysplasia?

Diastrophic dysplasia is a disorder of cartilage and bone development. Affected individuals have short stature with very short arms and legs. Most also have early-onset joint pain (osteoarthritis) and joint deformities called contractures, which restrict movement. These joint problems often make it difficult to walk and tend to worsen with age. Additional features of diastrophic dysplasia include an inward- and upward-turning foot (clubfoot), progressive abnormal curvature of the spine, and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth (a cleft palate). Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.

The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis type 2; however, diastrophic dysplasia tends to be less severe. Although some affected infants have breathing problems, most people with diastrophic dysplasia live into adulthood.

Read more about atelosteogenesis type 2.

How common is diastrophic dysplasia?

Although the exact incidence of this condition is unknown, researchers estimate that it affects about 1 in 100,000 newborns. Diastrophic dysplasia occurs in all populations but appears to be particularly common in Finland.

What genes are related to diastrophic dysplasia?

Diastrophic dysplasia is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.

Read more about the SLC26A2 gene.

How do people inherit diastrophic dysplasia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.