I found the reason why glucosamine, hyaluronic acid are used as much as health food. I found anti-aging reagent: sulfo disaccharides which co-working with Klotho. The disaccharides have glucosamine structure and similar structure with hyaluronic acid and chondroitin. Relations of the disaccharide, Klotho, hyaluronic acid, chondroitin, glucosamine with health and anti-aging were studied. Klotho makes disaccharide from glucosamine and glucuronic acid and co-works on site with produced disaccharide and gives stable Ca homeostasis and consequent health; anti-aging and long life. Fish is best food to get anti-aging and long life. The earth is warmed by burning of fossil and large amount of CO2 and NOx are emitted. Many developed countries eliminating NOx as pollution gas. Then CO2 assimilationist and plankton growth are blocked and fish production is blocked. I am insisting NOx elimination should be stopped to produce enough fish to get anti-aging and long life and to protect global warming.
Anti-aging and long life is dream of persons for thousand years.Average life of Japanese is men 80.50 (third), women 86.83 (top in the world). I wonder why Japanese live longer than other country. I believe that Japanese food based on fish is fit and good for long life. Fish contain glucosamine, hyaluronic acid and chondroitin. Glucosamine, hyaluronic acid, chondroitin are now used as health food by many persons in Japan. Suntory sold more than 20 million bottles of glucosamine and chondroitin as nutrition supporting food. Setagaya shizenshokuhin sold 200 million bags of glucosamine, hyaluronic acid and chondroitin as health food for 14 years. Taishoseiyaku are selling glucosamine and chondroitin. Zeria Shinyaku is selling chondroitin as medicine for 60 years. Wada calcium pharmaceutical sold 10 million bags containing glucosamine, chondroitin sulfate and collagen as nutrition supporting food. About 7 million persons are drinking and eating these materials and enjoying health and long life. Japanese eat fish contains glucosamine, hyaluronic acid and chondroitin. Food will be concerned with long life. I tried to find the reason way glucosamine; hyaluronic acid and chondroitin are so effective by the studies of glucosamine derivatives. I found one reason why these compounds are connected with health and long life. I found anti-aging reagent. This anti-aging gene is produced by Klotho (anti-aging gene) from glucosamine, chondroitin.
Glucosamine, hyaluronic acid, chondroitin are now used as health food by many persons in Japan. Suntory sold more than 20 million bottles of glucosamine and chondroitin as nutrition supporting food. Setagaya shizenshokuhin sold 200 million bags of glucosamine, hyaluronic acid and chondroitin as health food for 14 years. Taishoseiyaku are selling glucosamine and chondroitin. Zeria Shinyaku is selling chondroitin as medicine for 60 years. Wada calcium pharmaceutical sold 10 million bags containing glucosamine, chondroitin sulfate and collagen as nutrition supporting food. About 7 million persons are drinking and eating these materials and enjoying health and long life. Japanese eat fish contains glucosamine, hyaluronic acid and chondroitin. Food will be concerned with long life. I tried to find the reason way glucosamine; hyaluronic acid and chondroitin are so effective by the studies of glucosamine derivatives. I found one reason why these compounds are connected with health and long life. [1-7] I found anti-aging reagent. This anti-aging gene is produced by Klotho (anti-aging gene) from glucosamine, chondroitin. Anti-aging reagent co-work with Klotho and contribute for anti-aging and long life. Therefore glucosamine and chondroitin are effective food for anti-aging and long life. [8, 9].
I wish to recommend eating fish. But I found fish production of Japan decreased rapidly to 0-10 % of most fish production year 1970. I investigated the reason why fish production of Japan decreased so rapidly. I found that NOx and NP in waste water are eliminated as pollution substance almost completely. Plankton growth is inhibited and fish and sea weed cannot grow at such NP low concentration of sea. Fish price increased 5 times and we cannot buy fish easily and we cannot live longer. We may lose long life record of Japan. I am now insisting that NOx, NP elimination should be eliminated to increase NP concentration of sea to promote plankton CO2 assimilation to increase fish production. [10-14]
Klotho and sulfo- disaccharide
Nabeshima found that mutation of mouth Klotho gene leads to a syndrome resembling aging .The mouse having this gene can alive 30% longer. Since then many reports [16-45] are published. Petotou et al  reported that saccharides are involved in the binding of Klotho and FGF. Martin -Lumas report the activation of fibroblast growth glucuronidase capable factors by heparin  Klotho is a nobel β-of hydrolyzing β glycuronides  Nabeshima found a sulfo disaccharide from mouse liver cell. This saccharide binded with αKlotho and regulated the binding of αKlotho and FGF23. Mass analysis of this compound showed Mass number 843.28.C30H49N7O19S. Corresponding Thr-His-Gln-O-(β-D-3-sulfo-glucuronosyl) (1-4)-2-acetoamid-2- deoxy-D-glucopyranoside 9205 I planned to identify the real structure of this natural disaccharide by organic synthesis starting from known starting materials. Several disaccharides having similar structures were synthesized and relation of chemical structure and binding activity with Klotho and FGF 23 were studied [1-9]
Synthesis of sulfo disaccharide and measurements of binding activity
I have synthesized following compounds and measured their binding activity with Klotho and FGF23  Synthesis of 9294; p-methoxyphenyl-3-sulfo-p-beta-D-glucronosyl-(1-4) - acetoamino-3-deoxy-glucopyranosyside 9294 is synthesized from 2 easily and this is most easily obtainable ant-aging reagent .
Structure activity relationship
9188,9583,9279,9244 were measured. The activities of these 5 compounds were almost same activity irrespective of (1-4) or (1-3) bond, glucopyranoside or galactopyranoside, p-methoxyphenyl, or esteron, or serine .
Structure of sulfo disaccharides
I planned to determine chemical structure of natural disaccharide by synthesis. But I cannot determine (1-3) bond or (1-4) bond. Because both bond compounds showed activity. Disacharides have close relation with hyaluronic acid and chondroitin. Hyaluronic acid and chodroitin have (1-3) bond. Therefore I wish to propose (1-3) bonded two structures: Sulfo-Glucuronosyl (1-3)-Glucoside , Sulfo-Glucuronosyl(1-3)-Galactoside as natural disacharides
Relation of Klotho, sulfo-disaccharide, glucosamin, hyaruronic acid and chondroitin
Klotho is an enzyme that in humans is encoded by the KL gene  This gene encodes protein that is related to β-glucuronidases. Klotho is a novelβ-glucuronidases . β-Glucuronidase is an enzyme that can cleave glucuronosyl bond and this enzyme must do reverse reaction that is this enzyme can bind glucuronosyl group. Therefore Klotho can make disaccharide from glucuronoic acid and glucosamine.
Hyalunoic acid is poly(glucuronosyl(1-3)glucoside)
and chondroitin is polt(glucuronosyl(1-3)galactoside).
Hyalunoic acid gives gulcronic acid by Klotho
Chondroitin gives glucronyic acid by Kloth
Depolymerization of chitin gives N-acetylglucosamine. Depolymarization of chitosan gives glucosamine
Klotho combine glucronic acid and glucosamine to afford disaccharide
Klotho co-work with produced disaccharide on site to afford stable Ca homeostasis and subsequent Health and Anti-aging
These schemes indicate that Klotho is playing multiple roles.
1) Production of glucuronic acid
2) Production of disaccharide
3) Production of stable Ca homeostasis co-working
with disaccharide These schemes show that disaccharides, Klotho, hyalunoicacid, chondroitin, glucosamine are working closely related all together and giving us health and anti-aging. Klotho is a regulator of Calcium homeostasis  working with produced disaccharide Klotho makes disaccharide from glucosamine and glucuronic acid and co-works with produced disaccharide on site and gives stable Ca homeostasis and consequent health and anti-aging.
When we look at glucosamine derivative from natural products, we can find many compounds like hyalunoic acid, chondroitin, chondroitinsulfate, chitin, chitosan, keratan sulfate, proteochonroitinsulfate (chondromuco protein). Hyalunoic acid is poly (glucuronosyl (1-3)glucoside) and chondroitin is polt(glucuronosyl(1-3)galactoside). Soft bone, cartilage: Proteochonroitinsulfate is proteio-glycan aggregate composed of hyarunoic acid and core-protein.
Anti-aging foods [7-9]
Following story exists for long time, never throw away umbilical cord, naval string and keep it at poulownia chest of drawers for long time, and when you get incurable sickness, boil it in water for long hours, then drink the solution , then heavy sickness will be cured. I wish to explain the reason why umbilical cord (main component is hyaluronic acid) is so effective Hyaluronic acid is a main umbilical cord (connecting constitutional substance of naval string, an tubes between placenta of mother and unborn-baby for the supply of nutrition). Hyaluronic acid was first isolated from the bovine vitreous body in 1934 by Karl Meyer, a professor at Colombia University. The name hyaluronic acid is derived from hyaloids which means vitreous body in Greek. Hyaluronic acid is a linear polysaccharide. It has a repetitive structural unit composed of the disaccharides N-Acetyl D-glucosamine and D-glucuronic acid. Hyaluronic acid in our bodies generally exists as a high molecular weight of several million times. Hyaluronic acid, chondroitin, glucosamine are now sold from several companies as health food and several million persons are drinking and eating these materials and enjoying health and long life. By the studies of disaccharide, I found the reason why these compounds are consumed as health food. For good health, anti-aging and long life, eating of food containing hyaluronic acid, chondroitin, glucosamine and derivative is essential.
Eating of fish, whole body or head of fish or eye of fish, like sea bream(tai), house-macckerel (aji), mackerel pike (sanma), sardine (iwashi), shirasu (small sardine), iriko (boiled and dried small sardine),mezashi (dried sardine),shishamo, ayu, gold eye sea bream(kinme dai), loach(dojou), eel(unagi),carp(koi), curucian carp(funa), flat fish(hirame,karei),sand lance (ikanago), silver stripe rouna heming(kibinago),stone fish (okoje),blach rockfish(mebaru),herring(nishin), tsumire(crashed mixture of small fish), shark fin(fukahire), tsukudani of small fish, Among fish, clammy (nurunuru) fish like eel, anglerfish (ankou),loach, cat fish(namazu),sea cucumber(namako),octopus(tako),moray eel(utsubo), pike congera sea eel(hamo),clammy turtle (suppon) are good as anti-aging food, because main component of clammy substance at skin is chondroitin. Eating of eel (unagi no kabayaki) at hottest day of the year(doyono ushinohi) is popular as health food in Japan. Eel is served without head. But if it served with head, the efficiency will be increased. Anglerfish (ankou) is delicious and whole body is eaten. Octopus is clammy and dried under sun and eaten as health food. But octopus is washed with washing machine and clammy chondroitin is washed away. This octopus is not as effective as unwashed one.Turtle (suppon) is clammy and famous as delicious anti-aging food. Husk of shrimp and crab is composed with chitin and chitosan. Depolymerization of chitin gives N-acetyl glucosamine. Depolarization of chitosan gives glucosamine. Eating of shrimp and crab with head and husk is recommended. Eating of nebaneba (stringy and sticky) vegetable like sea tangle, kelp, mozuku, yam? nattou(fermented soybean)is recommended. Eating of cartilaginous cow, pig and chicken tissues is recommended. Hyaluronic acid was isolated from eyeball of cow and was named from Greek name glassily hyaloid. Hyaluronic acid is found in the highest concentrations at eye and joints. Most chondroitin appears to be made from extracts of cartilaginous cow and pig tissues (cow trachea and pig ear and nose, pig pitreous gel, but other sources such as bird cartilage are also used. The people who do not like to eat fish are advised to eat tablet of glucosamine, hyaluronic acid and chondroitin. Nonfood benefit of hyaluronic acid Hyaluronic acid is used for anti-aging skin handling , wound Healing [47, 48] cosmetic use . Hyaluronic acid has been used to treat osteoarthritis of the knee via injecting it into the joint [50, 51].
Relation of plankton CO2 assimilation, fish production and NOx [10-14]
360 Billion tone CO2 was produced in the world in 2016 by the burning of 140 billion tone fossil. To protect global warming, we must fix CO2 same amount of CO2 as emission. We are emitting 360 billion tones CO2. We are fixing 283 billion tone .Therefore 142 billion tone CO2 is in creasing. We must fix 142 billion tones CO2 by proportion of emission of each country. NOx: Amount of NOx is estimated from the fact that NOx is produced about 1/25 of produced CO2. The ratio C/N = 25/ 1 is same as plant composition ratio C/N = 25/1. Plant eat CO2 and nutrient N by the ratio C/N =25/1. 14.4 billion tone NOx is estimated to be produced when 360 billion tone CO2 is produced. Many governments such as United State, Japan , Germany ,United Kingdom ,France consider NOx as pollution gas and eliminated NOx by the reaction with ammonia. They ignored the importance of NOx as fertilizer. Amount of NOx is so much, CO2 assimilation is retarded very much. CO2 fixing is retarded very much. And global warming is accelerated very much. For the production of ammonia, much fossil is used and much CO2 is produced and global warming is accelerated so fast. World fish production in 2016 increased to 200 million tone, about double of 93 million tone in1997. China produced 79.38 million tone, Indonesia 22.21, India 10.11,Vietnam 6.21increasing fish production very much. Japan produced 16 million tone fish, top in the world in 1960 but fish production decreased to 4.64 million tone 7th place in 2016. This is huge decrease. Japan is eliminating 3 million tone N and P since 1980. Therefore NP concentration of sea decreased remarkably. Plankton cannot grow at this low concentration. Therefore fish decreased. 12 million tone fish was not produced in recent years. Japanese can alive longest by eating fish as main protein source. Because fish contain hyaluronic acid, glucosamine and chondroitin which precursor of anti-aging reagents which co-working with anti-aging gene Klotho [1- 9] Japanese may lose long life record. (Men 80.50 (third), women 86.63 (top) from the fact that fish production was reduced remarkably by NOx elimination law.
We can live longer by eating food containing glucosamine, chondroitin. I recommend you to eat fish and cartilaginous caw, chicken tissue. Eating of nebaneba (stringy and sticky) vegetable like sea tangle, kelp, mozuku, yam nattou (fermented soybean) is recommended. Because anti-aging gene Klotho makes anti-aging disaccharide from glucosamine and glucuronic acid and co-working with produced disaccharide and contribute to Ca homeostasis and subsequent health and anti-aging. Glucosamine, chondroitin and hyarunoic acid are starting material to make anti-aging reagents : sulfo disaccharide. NOx elimination should be stopped to get much fish and protect global warming.
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