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Why do older people, and animals, look different than younger ones? This has to do with changes in the proteins of the body. Proteins are the substances most responsible for the daily functioning of living organisms, which gives protein deterioration its dramatic impact on the body's function and appearance. Many lines of research over the last decade converge on protein modification as a major pathway for aging and degenerative disease. These modifications result from oxidation (as by free radicals) and interrelated processes such as glycation.
Our body is made up largely of proteins. Because the body's antioxidant system and other lines of defense cannot completely protect proteins, they tend to undergo destructive changes as we age, due largely to oxidation, glycation and another process called carbonylation. In other words carbonyl groups (>C=O) adhere to the protein molecules (and phospholipids as well). As a result the proteins break up in a process called proteolysis. Since protein carbonylation clearly preceded the loss of membrane integrity, it may be associated with the toxic process leading to cell senescence and death. In order to understand the implications of the proteolytic decline and buildup of aberrant proteins, it is necessary to revise the picture.
These interrelated protein denaturation and proteolysis include oxidation, carbonylation, cross-linking, glycation and advanced glycation endproduct (AGE) formation, as explained above. They figure prominently not only in the processes of ageing but also in its familiar signs such as skin aging, cataracts and neurodegeneration (i.e., loss of memory and dementia). A vast number of scientific studies, published by investigators in the east and west, show that carnosine is effective against all these forms of protein denaturation. Carnosine reacts with the carbonyl group and form an inert protein-carbonyl-carnosine adduct, thus protecting the proteins and reversing the denaturation.
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How does carnosine do this?
Carnosine simply restores the normal cell cycle control. To understand how this can happen, consider an engine whose oil isn't changed regularly. When the detergent in the oil is used up, contaminants precipitate and sludge forms on vital engine parts. The sludge accumulates, impairing engine performance, until finally the engine dies. The body too needs an efficient sludge removal system. When protein "sludge" accumulates, the gears of the cell cycle can get clogged up. This could impair the efficiency of cell division, and perhaps more importantly, enable damaged cells to reproduce. The result is increasing chromosomal instability, leading to degeneration and cancer. Another possible outcome is cellular senescence, when the cell cycle grinds to a halt. Protein carbonylation thus becomes a potentially terminal condition. Carnosine behaves us to maintain healthy intact proteins and to ensure their timely turnover.
Carnosine seems to be far superior to traditional antioxidants, e.g., vitamin E and selenium, that are not as effective as we hoped in the past. They do suppress some of the many pathways involved, while having no effect upon the others, like glycation and carbonylation. It has been established beyond question that antioxidants perform a crucial biochemical function in preventing reactive oxygen damage. However expecting an antioxidant to protect proteins against every form of glycation and carbonylation is like attempting to build a house with only a screwdriver - an essential tool, but incapable of replacing the rest of the toolbox.
Carnosine, natures multipurpose tool for protein protection, was designed by evolution to control the many factors that cooperate in degrading the bodys proteins. The chemical side-reactions that erode biological structure and function in the course of ageing result from toxic effects of the most basic elements in the bodys chemistry-oxygen, sugars, lipids and essential metals. We cannot do without these biochemical elements, but nutritional science is now giving us the understanding to better control their side effects.
Proteins are not the only molecules denaturated by carbonylation - phospholipids are carnonylated as well. And the carbonylation of phospholipids cause damage particularly in the central and peripheral nervous system, resulting in memory impairment and other deterioration of cognitive skills. As carnosine fights carbonylation of the phospholipids as well, it is now wonder that this dipeptide is a marvelous neuroprotectant, as we will see further on.
In sports and body building carnosine is involved in the detoxification pathway of reactive aldehydes from lipid peroxidation generated in skeletal muscle during physical endurance (Aldini et al. 2002a,b). Hence carnosine protects the skeletal muscles from injury, increases muscle strength and endurance and speed up recovery after strenuous exercise, as I will explain in detail later on in this review.
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