Secret of Anti-Aging: Anti-Aging Food Containing Glucosamine, Hyaluronic Acid and Chondroitin

Review Article

Secret of Anti-Aging: Anti-Aging Food Containing Glucosamine, Hyaluronic Acid and Chondroitin

Corresponding author: Shoichiro Ozaki, The Institute of Physical and Chemical Research, 2-1 Hirosawa Wokoshi Saitama, Japan, Tel: 0467-67-0991; E-mail : ozaki-0991@jcom.zaq.ne.jp

Abstract

Glucosamine, hyanunoic acid,chondroitin are now used as health food by many persons in Japan. I will explain how hyaluronic acid, chondroitin, glucosamine are contributing to the health ,anti-aging and long life. Klotho(anti-aging gene) makes disuccharide (glucronosyl(1-3)(N-acetyl glucosamine) from hyalunoic acid. Sulfo glucronosyl(1-3)galactoside from chondroitin sulphate. Klotho co-works with produced disaccharide on site and gives stable Ca homeostasis and consequent health, anti-aging and long life. Secret of anti-aging and long life is to eat food containing hyaluronic acid, chondroitin and glucosamine.

Key words:aluronic Acid; Chondroitin; Anti-Aging; Anti-Aging Reagent; Anti-Aging Food; Long Life

Introduction

People are looking for materials effective for anti-aging and long life for many years. Average life in Japan : male is 80.50 (third), female is 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.

I found that disaccharides and hyaluronic acid, glucosamine and chondroitin are closely related with anti-aging and long life..

Hyalunoic acid, glucosamine, chondroitin are now used as health food by many persons in Japan. Suntory sold 20 millions bottles of glucosamine and chondroitin as nutrition supporting food. Setagaya shizenshokuhin sold 22 million bags of glucosamin , hyaluronic acid and chondroitin as health food for 11 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 glucosamin, chondroitin sulfate and collagen

as nutrition supporting food. About 6 million persons are drinking and eating these materials and enjoying health, anti-aging and long life. I found the reason why glucosamine.. hyaluronic acid and chondroitin are so much used.

Nabeshima found Klotho(anti-aging gene) [1]. Since then many reports about human Klotho [2], anti-aging [1-11],Ca homeostasis [12-15] and related papers [16-19] are published. Nabeshima found a sulfo disaccharide from mouse liver cell. This saccharide bind with Klotho and FGF23.

I have synthesized the sulfo disaccharide and proposed the mechanism how the disaccharide are related with hyaluronic acid and chondroitin [20-24]. I am now reporting these and show the way to get health, anti-aging and long life in detail.

Glucosamine Derivatives

When we look at glucosamine derivative from natural products, we can find many compounds like hyalunoic acid,chondroitin,chondroitinsulfate, chitin, chitosan, keratan

Cite this article: Ozaki S. Secret of Anti-Aging: Anti-Aging Food Containing Glucosamine, Hyaluronic Acid and Chodroitin. J J Physiology. 2016, 2(1): 013.

Jacobs Publishers 2

sulfate, proteochonroitinsulfate (chondromucoprotein). Hyalunoic acid is poly(glucuronosyl(1-3)glucoside) and

chondroitin is polt(glucuronosyl(1-3)galactoside).

OH

Structure of Sulfo Disaccharides

Active disaccharides have following structures. Sulfo-glucuronosyl(1-3)-glucoside, Sulfo-Glucuronosyl(1-3)- Galactoside

OH

HO O

HO OH

NH2

HOOC HO

HO3SO

OHO O

O A

OH NH

HOOC

O HO

Glucosamine

OH O

O

HOOC

OH OH

COCH3

Sulfo-glucuronosyl(1-3)-glucoside

OSO H

O

( O

HO OH

)n

(

NHCOCH3 HO

O O

O )n

HOOC

3 OH

OH NHCOCH3 O O

HO O A

Hyaluronic Acid Chondroitin

HO OH

NHCOCH3

HOOC

O

( O

HO OH

OSO3H OH

O

O )n

NHCOCH3

Sulfo-glucuronosyl(1-3)-galactoside

(A: attached molecule like estrone, p-methoxyphenyl, vitamin D, amino acid, oligo amino acid, protein).These compounds binded with Klotho and FGF23 indicating that these compound are co-working with Klotho.

Chondroitinsulphate A

OH

O

O

( HO )n

Relation of Klotho,Sulfo-Disaccharide, Glucosamin, Hyaluronic Acid and Chondroitin

Klotho is an enzyme that in humans is encoded by the KL gene [2]

chitin

NHCOCH3

This gene encodes protein that is related to β-glucuronidases. Klotho is a novelβ-glucuronidases [19]. β-Glucuronidase is a enzyme that can cleave glucuronosyl bond and can bind

be-ta-1,4-poly-N-acetyl glucosamin

OH

O

O

( HO )n

NH2

glucuronosyl group. Therefore Klotho can make disaccharide from hyaluronic acid and chondroitin.

Hyaluronic acid is poly(glucuronosyl(1-3)glucoside) and chondroitin is poly(glucuronosyl(1-3)galactoside)

Hyaluronic acid gives glucurosyl(1-3) N-acetyl glucosamine by Klotho

Chitosan

OH OH

HO

OSO3H

OH

HOOC HO

Klotho

OH

HOOC HO O

O O

( O O )n

O

( O O

HO OH

O HO

)n HO

NHCOCH3

O

O OH

OH NHCOCH3

OH NHCOCH3

Keratan Sulfate

Soft bone,cartilage: Proteochonroitinsulfate is proteio-glycan aggregate composed of hyaluronic acid and core protein.

Hyaluronic cid Glucuronosyl(1-3)N-Acetyl Glucosamine

Klotho co-work with produced disaccharide on site to afford

Chondroitinsulphate gives sulfo-glucronosyl(1-3) N-acetyl galactosamine by Klotho

stable Ca homeostasis and subsequent health and anti-aging.

OH

HOOC

O

OSO3H OH

O

Klotho

HOOC

HO O

OSO3H OH

O

HOOC HO

HO3SO

OHO

O

OH

O

A + Klotho stable Ca homeostasis

NH

Health

Anti- ageing

( O O

HO OH

)n HO

NHCOCH3

O OH

OH NHCOCH3

COCH3

These schemes indicate that Klotho is playing multiple roles.

Chondroitin Sulphate Sulfo-Glucronosyl(1-3)

N-Acetyl galactosamine Depolymerization of Chitin gives N-acetylglucosamine.

  1. Production of disuccharide from hyaluronic acid, chodroichin by glucuronidase
  2. Production of glucuronic acid , N-acetyl glucosamine and

OH

O O ( HO )n

NHCOCH3

OH

HO O

HO OH

NHCOCH3

N-acetyl galactosamine

  1. Production of disaccharides by combing of two sugars
  2. Production of stable Ca homeostasis co-working with

Chitin N- acetyl glucosamine

Depolymarization of Chitosan gives glucosamine

OH OH

disaccharide

These schemes show that disaccharides, Klotho, hyaluronic acid, chondroitin, glucosamine are working closely related all together and giving us heath , anti-aging and long life.

O O ( HO )n

NH2

HO O

HO OH

NH2

Klotho is a regulator of Calcium homeostasis [12,15] Klotho makes disaccharide from hyaluronic acid and chondroitin and

Chitosan glucosamine

Hyaluronic acid gives glucuronic acid and N-acetyl glucosamine by Klotho

co-works with produced disaccharide on site and gives stable Ca homeostasis and consequent health and anti-aging [20-22]. Therefore eating of hyalunoic acid and chondroitin rich food is essential for anti-aging and long life [23,24].

Anti-Aging Food

HOOC O

(

O HO

O

OH

O )n Klotho

OH

HOOC

HO

HO O + O

For good health, anti-aging and long life, eating of food containing hyaluronic acid, chondroitin, glucosamine and

HO OH

NHCOCH3

OH HO

HO OH

OH

NHCOCH3

derivative is essential. Eating of fish, whole body or head of

hyalunoic acid glucuronic acid N-acetyl glucosamine

Klotho combine glucronic acid and glucosamine to afford disaccharide

fish or eye of fishs, like sea bream(tai), house-mackerel(aji), mackerel pike(sanma), sardine(iwashi),shirasu(small sardine),iriko(boiled and dried small sardine),mezashi (dried sardine), smelt (shishamo), ayu, splendid alfonasine(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), black rockfish(mebaru),

HOOC OH

O

Klotho

OH

HOOC OHO O

herring(nishin), tsumire(crashed mixture of small fish), shark fin(fukahire), tsukudani of small fish.

HO OH

HO

OH

HO

+ HO

O HO

OH HO

NH2

O OH

OH NH2

Amoung 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

Jacobs Publishers 4

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 . These octopus is not so 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.DepolymerizationofchitingivesN-acetylglucosamine. Depolymarization 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, sea weed (mozuku), yam (yamaimo), 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 persone who do not like to eat fish are advised to eat tablet

of glucosamine, hyaluronic acid and chondroitin.

Non Food Benefit of Hyaluronic Acid

Hyaluronic acid is used for anti-aging skin handling [25], wound healing [26,27], cosmetic use [28]. Hyaluronic acid has been used to treat osteoarthritis of the knee via injecting it into the joint [29,30].

Conclusion

Secret of anti-aging and long life is to eat anti-aging food, in other word, to eat whole body of fish, and cartilaginous cow, pig and bird tissues.

Acknowledgements

The author wish to express gratitude to Dr Yoichi Nabeshima and Dr.Katsuhiko Mikoshiba for their advice and suggestion and Dr.Ryota Maeda for activity measurement and Dr Yukito Ito, Dr Yuji Matsuzaki and Dr.Hideki Ishida for helpful advices for the synthesis of compounds.

References
  1. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997, 390(6655): 45-51.
  2. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M et al. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998, 242(3): 626-630.
  3. Kurosu H, Yamamoto M, Clark J. D, Pastor J. V, Nandi A et al. Suppression of Aging in Mice by the Hormone Klotho. Science. 2005, 309(5742): 1829-1833.
  4. Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A et al. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci. U.S.A. 2002, 99(2): 856-861.
  5. Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chin. Med. J. 2004, 117(5): 742-747.
  6. Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M et al. Life Extension Factor Klotho Enhances Cognition. Cell Reports. 2014, 7(4):1065-1076.
  7. Nabeshima Y. Challenge of overcoming aging-related disorders J. Dermatol. Sci. 2000, 24(1): S15–21.
  8. Kuro-O,M. Klotho and aging. Biochimica Biophysica Acta. 2009, 1790 (10): 1049-1058.
  9. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima
  10. Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol. Endocrinol. 2003, 17(12): 2393-2403.
  11. Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chin. Med. J. 2004, 117 (5): 742-747.
  12. Zhang R, Zheng F. PPAR-gamma and aging: one link through klotho?. Kidney Int. 2008, 74(6): 702-704.
  13. Imura A, Tsuji Y, Murata M, Maeda R, Kubota K et al. alpha- Klotho as a regulator of calcium homeostasis. Science. 2007, 316(5831): 1615-1618.
  14. Fukumoto S. [Chronic kidney disease (CKD) and bone. Regulation of calcium and phosphate metabolism by FGF23/ Klotho]. Clin Calcium.2009, 19(4): 523-528.
  15. Nabeshima Y.[Discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis]. Clin Calcium. 2008. 18(7): 923-934.
  16. Nabeshima Y. Molecular function of α-Klotho in calcium
  17. homeostasis. Igakunoayumi. 2007, 222(3): 225-230.
  18. J. L. dePaz, M. Martin-Lomus . Eur J. Org.Chem. 2005, 1849- 1859.
  19. Rafael Ojeda, Jesus Angulo,Pedro M, Manuel Martin- Lumas. The activation of fibloblast grouth factors by heparin: Synthesis and structureal study of rationally modified heparin- like oligosaccharides. Can.J Chem. 2002, 80: 917-936.
  20. Tubeur C, Jean-Maurice Mullet, Bono F, H Maurice, J-M Petitou et al. Bioorganic and Medicinal Chem. 7: 2003-2012.
  21. Tohyama O, Imura A, Iwan A, Jean-Noel Freund, Henrissat R et al. Klotho is a novelβ-glucuronidases capable of hydrolyzing steroidβ-glucuronides J.Biological Chemistry. 2004, 279(11) : 9777-9764.
  22. Ozaki Shoichiro . Sulfo disaccharides co-working with Klotho. Studies on structure , structure activity relation and function. World.J of Pharmacy and Pharmaceutical Sciences. 2015, 4: 152-175.
  23. Ozaki Shoichiro, Glucosamine Derivatives Sulfo disaccharides co-working with Klotho. Nutrition and Food Science. 2015, 5: 416.
  24. Ozaki Shoichiro. Synthesis of anti-ageing reagent: Sulfo disaccharide co-working with anti-aging gene. Archeves of Medicines. 2015, 7(6): 17.
  25. Ozaki Shoichiro. Nutrition for good health, anti-aging and
  26. long life, Hyaluronic acid,glucosamine and chodroitin. Maternal and Paediatric. Nutrition Journal .2015, 1: e102.
  27. Ozaki Shoichiro Food containing hyaluronic acid and chondroitin is essential for anti-aging International J of Aging & Clinical Research . 2016, 1: 101-103.
  28. 25 Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M. Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture. J. Invest. Dermatol. 1989, 92(3): 326-332.
  29. Chen WY, Abatangelo G. Functions of hyaluronan in wound repair. Wound Repair Regen. 1999, 7(2): 79-89.
  30. Longaker MT, Chiu ES, Adzick NS, Stern M, Harrison MR. Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann. Surg.1991, 213 (4): 292-296.
  31. Edwards PC, Fantasia JE. Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers.Clinical interventions in aging. 2007, 2(4): 509-519.
  32. Rutjes AW, Jün P, da Costa BR, Trelle S, Nüesch E et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann. Intern. Med. 157(3): 180-191.
  33. Frampton JE. Hylan G-F 20 single-injection formulation. Drugs Aging. 2010, 27(1): 77-85.

Be the first to comment on "Secret of Anti-Aging: Anti-Aging Food Containing Glucosamine, Hyaluronic Acid and Chondroitin"

Leave a comment

Your email address will not be published.


*