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LE Magazine January 2006
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How Carnosine Protects Against Age-Related Disease

By Edward R. Rosick, DO, MPH, MS

Staving Off Neurodegeneration

Currently available pharmaceutical medications prescribed for Alzheimer’s disease do nothing to combat the damage caused by amyloid beta or oxidative stress, two key factors in the genesis of this devastating illness. Experimental studies, however, suggest that carnosine can help protect against both. By protecting the brain against free radical and AGE-induced damage, carnosine may provide a way to treat and manage Alzheimer’s disease.10,28-30

One early study examined the ways in which carnosine may protect the brain against the toxic effects of malondialdehyde, an end product of lipid peroxidation.29 Using cultured rat brain cells, researchers showed that carnosine not only protected the brain cells against malondialdehyde-induced toxicity, but also inhibited malondialdehyde-induced protein cross-linking.

More recently, researchers examined carnosine’s protective effects against amyloid beta.30 Using cultured rat brain cells, they showed that introducing amyloid beta to the culture caused significant toxic effects. The researchers then showed that damage to the brain cells could be substantially decreased by adding carnosine to the mixture. “We postulate that the mechanism of carnosine protection [of brain cells] lies in its anti-glycating and antioxidant activities, both of which are implicated in neuronal and endothelial cell damage during Alzheimer’s disease,” the researchers noted. “Carnosine may therefore be a useful therapeutic agent.”

Combating Heart Disease

Americans spend billions each year on expensive drugs designed to ward off and treat the secondary effects of atherosclerosis and coronary artery disease. Unfortunately, these costly, doctor-prescribed medications do nothing to prevent cardiac damage induced by AGEs and free radicals.

Multiple lines of study now indicate that carnosine may be a highly beneficial nutrient for people with heart disease.12,14,31,32 In a review article examining the role of free radicals and AGEs in atherosclerosis, researchers carefully outlined the ways in which oxidative damage and AGE toxicity can contribute to the formation of atherosclerotic plaques, a hallmark of heart disease.12 They then examined ways to impede plaque formation, concluding, “AGE inhibitors . . . will also inhibit the chemical modifications of proteins during lipid peroxidation reactions, and will prove useful in the treatment of atherosclerosis.”

The theory that AGE inhibitors such as carnosine may be a useful adjunct in both preventing and treating heart disease has been borne out in animal research as well. In two studies using dogs, researchers showed that AGE-induced changes led to decreased heart function by contributing to collagen cross-linking.14,32 When this happens, heart blood vessels, as well as the heart muscle itself, lose elasticity and become less efficient. When old dogs received an AGE inhibitor, they demonstrated a marked decrease in heart muscle stiffness as well as improved overall cardiac function.

Conclusion

By protecting against both free radical-generated oxidative damage and AGE-generated cellular toxicity, carnosine helps to counteract numerous, potentially harmful biochemical processes associated with aging. Its diverse effects offer support for the aging brain and cardiovascular system, and may help to modulate processes that contribute to cancer. Carnosine’s remarkable spectrum of health benefits makes this versatile nutrient an essential component of any anti-aging program.

References

1. Baynes JW. The role of AGEs in aging: causation or correlation. Exp Gerontol. 2001 Sep;36(9):1527-37.

2. DeGroot J. The AGE of the matrix: chemistry, consequence and cure. Curr Opin Pharmacol. 2004 Jun;4(3):301-5.

3. Harding JJ. Viewing molecular mechanisms of ageing through a lens. Ageing Res Rev. 2002 Jun;1(3):465-79.

4. Onorato JM, Jenkins AJ, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine. J Biol Chem. 2000 Jul 14;275(28):21177-84.

5. Vlassara H. Advanced glycation in health and disease: role of the modern environment. Ann NY Acad Sci. 2005 Jun;1043:452-60.

6. Baynes JW. The Maillard hypothesis on aging: time to focus on DNA. Ann NY Acad Sci. 2002 Apr;959:360-7.

7. Takeuchi M, Yamagishi S. TAGE (toxic AGEs) hypothesis in various chronic diseases. Med Hypotheses. 2004;63(3):449-52.

8. Munch G, Schinzel R, Loske C, et al. Alzheimer’s disease—synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm. 1998;105(4-5):439-61.

9. Sasaki N, Toki S, Chowei H, et al. Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease. Brain Res. 2001 Jan 12;888(2):256-62.

10. Dukic-Stefanovic S, Schinzel R, Riederer P, Munch G. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? Biogerontology. 2001;2(1):19-34.

11. Moreira PI, Smith MA, Zhu X, et al. Oxidative stress and neurodegeneration. Ann NY Acad Sci. 2005 Jun;1043:545-52.

12. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000 Jun 15;28(12):1708-16.

13. Schleicher E, Weigert C, Rohrbach H, et al. Role of glucoxidation and lipid oxidation in the development of atherosclerosis. Ann NY Acad Sci. 2005 Jun;1043:343-54.

14. Asif M, Egan J, Vasan S, et al. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci USA. 2000 Mar 14;97(6):2809-13.

15. Spiteller G. Is atherosclerosis a multifactorial disease or is it induced by a sequence of lipid peroxidation reactions? Ann NY Acad Sci. 2005 Jun;1043:355-66.

16. Athar M. Oxidative stress and experimental carcinogenesis. Indian J Exp Biol. 2002 Jun;40(6):656-67.

17. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004 Nov;266(1-2):37-56.

18. Abe R, Shimizu T, Sugawara H, et al. Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions. J Invest Dermatol. 2004 Feb;122(2):461-7.

19. Yamamoto Y, Yamagishi S, Hsu CC, Yamamoto H. Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B. Biochem Biophys Res Commun. 1996 May 24;222(3):700-5.

20. van Heijst JW, Niessen HW, Hoekman K, Schalkwijk CG. Advanced glycation end products in human cancer tissues: detection of Nepsilon-(carboxymethyl)lysine and argpyrimidine. Ann NY Acad Sci. 2005 Jun;1043:725-33.

21. Boldyrev AA, Stvolinsky SL, Tyulina OV, et al. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol. 1997 Apr;17(2):259-71.

22. Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc.). 2000 Jul;65(7):869-71.

23. Yuneva MO, Bulygina ER, Gallant SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Med. 1999;2(4):337-42.

24. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: a review. Curr Med Chem. 2005;12(20):2293-315.

25. Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5.

26. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol. 1998 Aug;30(8):863-8.

27. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc.). 2000 Jul;65(7):866-8.

28. Kohen R, Yamamoto Y, Cundy KC, Ames BN. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci USA. 1988 May;85(9):3175-9.

29. Hipkiss AR, Preston JE, Himswoth DT, Worthington VC, Abbot NJ. Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells. Neurosci Lett. 1997 Dec 5;238(3):135-8.

30. Preston JE, Hipkiss AR, Himsworth DT, Romero IA, Abbott JN. Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine. Neurosci Lett. 1998 Feb 13;242(2):105-8.

31. Jandeleit-Dahm KA, Lassila M, Allen TJ. Advanced glycation end products in diabetes-associated atherosclerosis and renal disease: interventional studies. Ann NY Acad Sci. 2005 Jun;1043:759-66.

32. Liu J, Masurekar MR, Vatner DE, et al. Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2587-91.