This theory states that  the ageing process may be simply the sum of the deleterious free radical reactions going on continuously though the cells and tissues.

I would like to use a few lines of my dissertation to define some concepts related to free radical chemistry in biological systems.

 Some molecules can  be divided in two parts. For example water, H20, can be divided into H. and OH.. Each part is called a free radical. The Hydrogen radical has one unpaired electron, and also the hydroxyl radical. In this case the chemical bond of water had an homolytic breaking, each of the two electrons in the chemical bond were retained by each fragment. Hydrogen and the hydroxyl radical, each  has now, one  unpaired electron.

The molecule of water, as other molecules, could cleave its bond  in a different way called heterolysis.  One fragment  takes the two electrons of the bond and the other fragment none. The part which has the two electrons OH-, has become negatively charged and the fragment which is deprived of electrons H+ is positively charged. Each part is now called an ion. In this case the  molecule of water, H2O, splits into the ions OH- and H+. The hydrogen ion and the hydroxyl ion. The hydrogen ion has lost its only electron and the hydroxyl ion has now a pair of electrons. These ions are free ( not bound by a chemical bond), but they are not free radicals because they have not unpaired electrons.

Molecular oxygen (O2), is a stable free radical that has two unpaired electrons. Each electron with a different spin. The stable molecular oxygen could be reduced to a much more reactive form called superoxide O2-,  on which  one electron became paired and the other electron remains unpaired. The site of this unpaired electron is extremely reactive, and many times too toxic for living systems. The discovery of the extremely reactive superoxide molecule, has provided the basis with which to elaborate the free radical theory of ageing.

The enzymes superoxide dismutases are essential components of the biological defense against superoxide toxicity. 

As explained before, oxidations are chemical reactions on which the oxidized part loses electrons. Auto-oxidations occur when molecules react with themselves to form products in the higher and lower oxidation state.

Several non-radical compounds "auto-oxidize" on exposure to oxygen from the air: examples are adrenalin, ascorbic acid, thiols and 6-hydroxidopamine (which is a catecholamine, like dopamine, and other amines of biomedical interest ).

The so-called "locura manganica" reported to affect miners of manganese-containing ores, is produced because manganese accelerates the oxidation of catecholamines like dopamine, to produce damaging oxygen radicals. Auto-oxidations of catecholamines generate superoxide. This occurs when a pair of electrons is released into the system. One electron is used to auto-oxidize the catecholamine and the other electron adds to molecular oxygen generating superoxide.

Catecholamines are the neurotransmitters, epinephrine and dopamine. Both amines  are known to be affected by the process of auto-oxidation.

Free radical damage  on the dopaminergic system of the brain is directly related to  atmospheric oxygen.

The neurotransmitter dopamine plays a crucial role.

One of the biochemical paths of the degradation of dopamine is to  be endogenous metabolized to 6-hydroxidopamine. This occurs when there is an excess of oxygen in dopaminergic areas of the brain, and superoxide have been previously generated.

  During the auto-oxidation of 6-hydroxidopamine, hydrogen peroxide is liberated with lethal effects to dopaminergic neurons (Color Plate 6, Page 51). Melanin is formed to absorb the hydrogen peroxide  in a  self-defense process.

 Neuro-Melanin, the black pigment found mainly in the substantia nigra of the brain uses hydrogen peroxide, tyrosine, dopa and peroxidase enzymes for its biosynthesis.  The defense of brain cells against the damaging effects of hydrogen peroxide  is clearly observed through the black melanin spots that forms the substantia nigra.

Ageing is characterized by a clear deterioration of the dopaminergic system of the brain. Dopamine cells are lethally affected with age.  The dopamine content of the human brain decreases by 13% per decade over age 45. The age-related progressive decline of dopaminergic control in the brain seems to be by now the first firmly established biochemical lesion of ageing.

It seems to me, that the main generator of this serious brain deterioration is superoxide, acting as the initiator of auto-oxidation reactions, leading to the damage and destruction of dopaminergic cells.

Superoxide induced lethal effects on dopamine producing neurons, causes dopamine deficiency, which in turn produces, rigidity, difficulties in speech, impaired movements, loss of flexibility, slow movements, and loss of memory, all these noticeable characteristics of senescence.

Another important effect of dopamine as a biological controller of senescence is  related to its direct inducing effect in the secretion of the growth hormone releasing hormone (GHRH) by the hypothalamus.

It has been demonstrated that dopamine is a stimulatory neurotransmitter in the secretion of human growth hormone. The firing of the tubero-infundibular dopamine neurons, enhances human growth hormone release via the pepti-dergic somatoliberin neurons of the median eminence.

Oral administration of L-Dopa is a well known provocative stimulus for human growth hormone release via the hypothalamus.

Recently a study published in The New England Journal of Medicine concluded that diminished secretion of growth hormone is responsible in part for the decrease in lean body mass, the expansion of adipose tissue mass and the thinning of the skin that occurs in old age.

Decrease in growth hormone secretion   may be produced because of dopaminergic damage  caused by oxygen and superoxide radical.

From the facts presented above, I concluded that atmospheric oxygen, is at the top of the sequence of events  inducing ageing

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