Drs Elmer Cranton and James Frackelton describe them, in an article entitled 'Free Radical Pathology in Age Related Diseases' published in The Journal of Holistic Medicine (1984 6(1)) as follows: 'Every free radical has an unpaired electron in an outer orbit, causing it to be highly unstable and to react almost instantaneously with any substance in its vicinity. These reactions often cause a cascade of new free radicals in a multiplying (chain-reaction) effect.' It is such free radical activity which allows high level radiation to damage and kill, as the rays (gamma, X, ultraviolet, cosmic etc.) knock electrons out of orbiting pairs, thus producing free radicals.

Radiation is one extreme of the range of this phenomenon, although some scientists describe the damage free radicals cause to cells in everyday life as 'continuous internal radiation'. Surprisingly perhaps, a good deal of free radical activity is produced by the body itself for specific purposes (killing bacteria for example and in detoxification processes). This phenomenon can therefore be considered to be 'controlled internal radiation'. Oxygen in its everyday form is an amazing substance which can either generate free radicals or can help to switch them off. As Cranton and Frackelton explain it:

A liter of normal atmospheric air on a sunny day will contain over one billion hydroxyl free radicals, whereas oxygen at normal physiological concentrations in living tissues neutralizes more free radicals than it produces. When oxygen levels are reduced (low), as occurs in ischemic tissues (lacking good blood supply and therefore poorly oxygenated) oxygen becomes a net contributor of free radical damage.

Some oxygen processes are more likely to produce large quantities of free radicals than others, and it is when there is either too much or too little oxygen present in a metabolic reaction that the worst situations arise. Evolutionary processes have fortunately helped to ensure that we can survive in an oxygen environment through the provision of an army of substances which protect us, with healthy body cells producing and/or using over a dozen antioxidant control substances.

What free radicals do
If cellular damage is a cause of ageing, and if we can slow down that damage, it makes sense to think that ageing can be retarded. For example, when free radical activity is taking place, damage to cells occurs, protein synthesis becomes impaired, proteins become cross-linked and tangled, tissues become less pliable, arteries incur damage leading to atherosclerosis, genetic material (DNA/RNA) is damaged leading to possible cancer development and to inefficient repair processes, age pigments accumulate which literally drown the cells in lipofuscin, preventing them from functioning, and in general all the signs and indications of ageing are promoted, whether this is stiffness, poor circulation or wrinkles (cross-linkage), not to mention diseases such as atherosclerosis, arthritis, cancer and, it is now believed, Alzheimer's disease.

Professor Alan Hipkiss, of King's College, University of London, writing in Human Ageing and Later Life (edited by Anthony Warnes and published by Edward Arnold, London, 1989) tells us that free radicals are also responsible for the damage which occurs in cataracts due to cross-linkage of proteins, and he says: 'Oxygen free radicals can also damage DNA which, if it is not repaired, could give rise to altered, mutant proteins.'

Some free radical activity is actually essential for good healthy functioning. For example, when certain of our immune functions are operating, say when white blood cells are attacking and deactivating invading micro-organisms (bacteria, viruses, fungi etc.) they generate free radicals in order to do their job. It should not be surprising to discover, therefore, that in the face of the flood of free radicals produced both by normal metabolism and other functions of the body, as well as those received from outside the body (radiation, low level radiation, cigarette smoke, environmental pollution, alcohol and many other 'contributors') our bodies have, of necessity, had to find ways of coping.

Can ageing due to free radicals be slowed down?
Professor Hipkiss is not sure. He says:

Ageing may be inevitable in complex organisms; indeed it is surprising that we live so long given the multiplicity of insults to which our cells are continuously subjected. Only homoeostatic mechanisms (self-repairing, self-balancing, including antioxidant functions) enable our survival. Maybe, if we wish either to live longer or to resist the ravages of time, we should design further homoeostatic systems to repair our repair systems.

Doctors Cranton and Frackelton dramatically underline the importance of dealing with free radicals:

When free radicals in living tissues exceed safe levels, the result is cell destruction, malignant mutation, tumor growth, damage to enzymes and inflammations, which manifest clinically as age-related, chronic degenerative diseases. Each uncontrolled free radical has the potential to multiply a million-fold. But, when functioning properly, our antioxidant systems suppress excessive free radical reactions.

They point out that the life expectancy of mammals (such as ourselves) is in direct proportion to the free radical control enzymes, like superoxide dismutase. The use of antioxidant and dietary restriction approaches would seem to be able to boost and enhance antioxidant activity, given the evidence accumulated to date. We are literally repairing the repair system (or allowing it to repair itself) when we fast or modify what is eaten in the manner suggested by Drs Weindruch and Walford's experiments. The question seems not only to be whether such repairs influence life expectancy rather than health, but also what are the best ways of achieving this end?

Since Dr Denham Harman of the University of Nebraska first proposed that free radicals were the keys to ageing, as far back as the mid-1950s, the study of ageing has spent much time examining the possibilities of slowing down both free radical damage and ageing. Recently, however, although the theory still looks accurate in many respects, some doubts have begun to be cast on just how antioxidant activity at cellular level can be achieved. Our self-produced defense against free radicals comes in the form of substances which literally sacrifice themselves so that the rogue free radical molecules are mopped up, thus preventing their ability to latch onto electrons in healthy tissues, and damaging or altering them in the process.

Amazing substances
Our bodies have evolved defensive substances such as the enzyme catalyst which can deactivate hydrogen peroxide (bleach), one of the substances our immune system uses in its own attacks on unwelcome, invading, micro-organisms. Catalase and other antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase, are also present as defenders of body tissues against oxidative processes. These enzymes are dependent upon a number of trace elements and vitamins (mainly of the B-complex group) for their function, including copper, zinc and manganese (for SOD), selenium (for glutathione peroxidase) and iron (for catalase).

There are also non-enzyme free radical deactivators, some of which are literally consumed in their battle against radicals, including beta carotene (the precursor of vitamin A),vitamins E and C, amino acids glutathione, methionine and cysteine, and the mineral selenium which is symbiotically active with vitamin E.

A surprise defender
One of the more surprising antioxidants, which we produce in our own cells, is cholesterol. This substance helps protect the cell membrane against free radical damage, as well as itself being a precursor of vitamin D. Vitamin D is formed by the body, from cholesterol in the skin, in response to radiation from sunlight (ultraviolet light). When too much vitamin D is formed in some tissues this attracts the deposition of calcium into cells in the region, in turn interfering with normal cell transportation functions and energy production.

The health benefits which have been seen as a result of reducing cholesterol in the diet seem to be a result of a coincidental reduction in fat intake, which reduces free radical potential (fats peroxidize easily under free radical attack.) However, use of drugs which reduce cholesterol levels in the blood (nine-tenths of which is self-produced rather than result of the food we eat) have had a history of side-effects, mainly because of the failure to recognize the protection cholesterol gives us as an antioxidant.

Another extremely powerful antioxidant, universally present in the system, is uric acid, which, although toxic in excess, is easily metabolized by the body if adequate nutritional levels of vitamin C are present.

What about ageing?
Now, since we know that antioxidants can slow down or switch off free radical activity, should it not be the case that ageing automatically slowed down when these are supplied in increased quantities? Weindruch and Walford are not sure, saying that feeding antioxidants to animals has so far failed to demonstrate increase in life span (this statement has been challenged, see below They suggest that the 'excuses' which believers in oxidant nutrition offer for this failure are that the antioxidants given to the experimental animals may not be able to penetrate he sites of free radical activity in the cells, or that the body adjusts its own production of natural antioxidants downwards when these are supplemented in the diet, so that no net gain is seenin antioxidant activity (and therefore no improvement in terms of lessened damage or life expectancy). The second 'excuse' come at least partially accurate. As mentioned previously, we come equipped with a wide array of self-repair and protection mechanisms including an assortment of antioxidant enzymes which quench free radicals.

Evidence
Richard Cutler of the National Institute of Aging in the US , studied more than 20 species, including rats and humans. In cases those that live longest have the highest and most active levels of antioxidant enzymes which literally soak up free radical activity (remember a squeeze of lemon juice on a browning apple, rust-proofing metal?). However, some studies show that when antioxidants such as vitamin A are provided, cells respond by reducing their own production of antioxidants, allowing the same amount of free radical activity to continue. This does not stand as absolute proof that antioxidant methods are not going to work, but certainly puts a question mark on just how this can best be achieved, and I tackle this later in the book.

One argument against free radical damage being a major cause ageing is based on the fact that the ageing process seems to a well-organized progression, whereas the damage cause by e radicals appears more chaotic and random. So, although it might well be that most if not all the major diseases of old age have roots which link them to free radical damage, this does not necessarily connect ageing itself to the activity of free radicals, only to poor health.

Genetics again
There is also the argument that when a certain degree of damage has taken place on a cellular level, a preprogrammed, genetically based process might be called into play, a sort of 'self-destruct button' having been pressed. Just when this happens will depend upon the degree of damage caused by free radicals (or other factors), which are themselves to a large extent the product of the rate at which metabolic activity is going on, which takes us back to the 'thrifty' and 'burner' types described by Weindruch and Walford.