How Carnosine Protects Against Age-Related DiseasePrint
By Edward R. Rosick, DO, MPH, MS
|Proteins are the building blocks of life. Comprising amino acid chains, proteins serve both structural and functional roles within the human body. Structural proteins such as collagen give support to bones, tendons, and skin, while functional proteins known as enzymes catalyze life-sustaining biochemical reactions throughout the body.|
As we age, however, these critical proteins are endangered by the damaging process known as glycation. Defined as a non-enzymatic reaction between proteins and sugars, glycation irreversibly alters the configuration of proteins. These altered proteins, known as advanced glycation end products (AGEs), can no longer effectively fulfill their critical roles throughout the body. AGEs have been implicated in many of the diseases associated with aging.
Fortunately, a powerful nutrient called carnosine helps defend the body’s proteins against the crippling effects of glycation. By preventing the formation of dangerous AGEs, carnosine may help the body’s proteins retain their youthful vigor and function. Moreover, studies demonstrate that carnosine is also a powerful antioxidant. Carnosine’s age-defying effects make this critical nutrient an essential cornerstone of every anti-aging program.
AGEs, Aging, and Free Radicals
Many people, especially those well versed in anti-aging medicine, are knowledgeable about free radicals. Far fewer are familiar with advanced glycation end products, or AGEs, molecules that may be just as important as free radicals in initiating the pathological processes associated with aging. AGEs are substances formed in the human body by the biochemical interaction between carbohydrates and proteins in a process known as the Maillard reaction.
Interestingly enough, the Maillard reaction was first noted during the heating of foods in the presence of sugars; it is what gives cooked foods their unique texture, taste, and smell. One author of a study of AGEs made the following analogy: “the human body might be viewed as an extraordinary complex mixture of chemicals reacting in a low temperature (37° C) oven with a 76-year cooking cycle.
Under these conditions, non-enzymatic reactions between carbohydrates and proteins, known collectively as Maillard or browning reactions, produce a wide range of age-related chemical modifications and cross-links in tissue proteins.”1
This cross-linking of proteins with carbohydrates can have wide-reaching effects, as AGEs are known to have deleterious effects on the structural and functional properties of proteins and the tissues in which these proteins reside. When you consider that proteins are present everywhere in the human body, the destructive capability of AGEs becomes quite clear.
While AGEs are destructive in their own right, their interplay with free radicals causes even more havoc in the aging human body. Researchers now postulate that oxidative stress may be involved in AGE formation and that, in a vicious cycle, AGEs may induce even more oxidative stress. In fact, most AGEs that accumulate in proteins are produced under oxidative conditions.
As these AGEs and free radicals accumulate in cells and tissues, molecular damage and degradation down to the level of DNA increases, leading to many of the conditions associated with growing old.
A growing body of sound scientific evidence theorizes that AGEs and similar molecules such as advanced lipoxidation end products, or ALEs (the products of lipids cross-linking with sugars), are significant contributors to many common pathological processes leading to.2-7
Carnosine’s Protective Effects
Inhibiting the formation of AGEs and associated molecules is thus an essential part of any anti-aging protocol. According to a paper on how AGEs affect aging, “Inhibition of AGE/ALE formation is a reasonable target for life-span extension for several reasons”.
First, if damage to protein reflects damage to DNA, then inhibition of AGE/ALE formation . . . should limit damage and mutation in DNA, leading to an increase in maximum life span.
Second, accumulation of AGE/ALEs in proteins is associated with a number of age-related, chronic diseases . . . inhibition of AGE/ALE formation might delay the progression pathology in these diseases, thereby improving the quality of life in old age.
A third consideration is that inhibition of AGE/ALE formation might also limit secondary oxidative damage to biomolecules.”1
Carnosine is a safe, well-tolerated compound comprising the amino acids beta-alanine and L-histidine. Naturally present in high concentrations in human brain and skeletal muscle tissue, carnosine has been shown in multiple studies to inhibit lipid peroxidation and free radical-induced cellular damage.
Additional evidence suggests that carnosine may help protect the brain against oxygen deprivation,11 delay the impairment of eyesight with aging,12 and extend the life span of mammals.13 In addition, scientists have now shown that carnosine can effectively inhibit AGE formation and protein cross-linking.10, 14-17
Because it is able to both stop the oxidative damage of free radicals and inhibit AGE formation, scientists have postulated that carnosine may have applications in the management of numerous conditions.
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. Carnosine’s remarkable spectrum of health benefits makes this versatile nutrient an essential component of any anti-aging program.
|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. 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.
12. 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.
13. 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.
14. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: a review. Curr Med Chem. 2005;12(20):2293-315.
15. 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.
16. Hipkiss AR. Carnosine, a protective, anti-ageing peptide? Int J Biochem Cell Biol. 1998 Aug;30(8):863-8.
17. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc.). 2000 Jul;65(7):866-8.