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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. |
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, nature’s
multipurpose tool for protein protection, was designed by evolution to control
the many factors that cooperate in degrading the body’s 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 body’s 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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