As I explain in Chapter 9, there is much evidence to support the importance, in the delaying of ageing, of lowering internal temperature levels, which naturally enough means slowing down metabolic processes. When metabolic processes are slower, free radical activity slows down, and ageing is delayed. Once again we see the interconnection between one aspect of the picture with another - slow metabolism, leading to less free radical damage, leading to less cellular damage and disease, leading to lesser likelihood of programmed obsolescence via the genes being triggered.

The idea that a genetic programme exists which decides that enough is enough, and that ageing should be accelerated is not completely fanciful, as it fits into some of the evolutionary concepts which I have previously talked about. It is quite certain that antioxidant techniques can lead to a reduction in oxidation damage caused by free radicals, resulting in improved health (both in animals and humans). It is also reasonably certain that youthful qualities can be generated by such an approach, but what remains very unclear is whether this would have any noticeable impact on life expectancy.

Can anti-free radical approaches lengthen life?
Over the years, three approaches to 'using' the understanding of free radical activity for promotion of life extension have been suggested:

1. Employment (in the diet) of free radical deactivators (antioxidants) such as vitamins A, C, E, and B6; minerals zinc and selenium; amino acids cysteine, methionine and glutathione, as well as enzymes such as SOD and catalase (which are now known to survive the bodys digestion process and to be able to increase tissue levels when supplemented in certain forms, such as freeze-dried wheat grass juice). Some (e.g. Pearson and Shaw) also recommend the use of artificial substances such as BHT in this quest (see below).

2. Reduction in the diet, as far as is possible, of foods and substances which add to the free radical burden, including polyunsaturated fats and metals such as copper. A logical extension of this sort of tactic would be to avoid wherever possible exposure to environmental pollution, whether in the workplace or at home, as well as curbing lifestyle habits which might add to the burden (smoking and alcohol consumption, for example).

3. Dietary restriction, which reduces metabolic rate, and therefore free radical activity, as well as actually increasing the presence of some of the most important antioxidants. Some experts suggest that one of the main reasons why dietary restriction actually increases life span is its effect on free radicals.

Some of these approaches might seem to be more health enhancing than life span extending, but it is almost impossible to distinguish which is which. It seems, therefore, that there is no good reason for not trying to include all three elements of this approach, and I deal with this in greater detail in the section on strategies.

Antioxidants and life span increase
Durk Pearson and Sandy Shaw (in their book Life Extension) quote the work of Dr Denham Harman, who looked at increasing life span by using artificial antioxidants such as BHT (butylated hydroxy-toluene) a substance frequently used as a food additive to protect against spoilage (commonly by free radical activity). BHT was shown by Dr Harman to increase the life spans of mice, initially in those which normally had a short life span due to the spontaneous development of cancer. Critics of this type of evidence for life extension by use of antioxidants suggest that it is only the prevention of cancer which lengthened' the lives of these animals, which in any case did not exceed the norm for the species. Dr Harman has subsequently also produced evidence of life extension in normally long-lived, non-tumour generating mice, using BHT.

A variety of other experiments on mice, chickens and other creatures hint at life span being extended by use of antioxidant nutrition. For example, a report from the Department of Biochemistry, University of Louisville School of Medicine (Proceedings of Society of Experimental Biology and Medicine (1986 183(1):81-5) by Drs J. Richie, B. Mills and C. Lang showed that the use of a powerful artificial antioxidant nordihydroguaiaretic acid (NDGA) could increase the life spans of insects by between 42 and 64 per cent. NDGA was either added to the medium in which larvae developed or to adult mosquito diets (involving different ages and sexes). Young adults and active larvae were the best responders. The researchers make the point that this evidence is important since it demonstrates life extension without dietary restriction.

Why mosquitoes, and do results such as this mean anything in human terms?
Insects have a short life expectancy, and experiments can be conducted which do not have to be spread over many months or years (even mice experiments on life extension take years). They do have implications for humans since, as has been demonstrated by so many researchers into dietary restriction, the effects are found in ALL species tested to date. If life extension is achieved in mosquitoes using dietary restriction, and if it is also achieved using antioxidant nutrition, we can read into this the implication that it would probably help us as well.

Pearson and Shaw quote numerous studies which support the idea of antioxidant supplementation helping health and longevity, however much of this seems (as in the report on the mosquitoes) to involve synthetic substances. For example, they quote studies by Dr Harman involving mice in which senile changes were prevented by use of synthetic antioxidants such as Santoquin, commonly used as a stabilizer in commercial chicken feed, and found to have an unexpected bonus in that it seems to keep chickens laying longer by slowing their ageing processes. As well as retarding the senile changes, this substance also increased the life spans of the mice by between 30 and 45 per cent - equivalent, Pearson and Shaw tell us, to a human life span of 100 years. What that really amounts to is not life extension (since our true life expectancy is around 120) but a definite improvement on our present average life span.

This artificial antioxidant acts, according to Pearson and Shaw, 'in all metabolic functions' exactly like vitamin E, one of the most powerful of all antioxidants. It is tempting to ask why vitamin E is not therefore used in chicken feed? One answer might be that there is no patent on vitamin E and therefore there would be little commercial advantage to the company producing and marketing this feed additive, since anyone else could simply copy the product. A less cynical answer might be that when the body receives a quantity of an antioxidant which it should be producing for itself, there may occur an automatic reduction in its own production, leaving a no-gain situation in terms of potential for deactivating free radicals (as seen in the supplementation of vitamin A).

Could it be that the body does not recognize the artificial antioxidants as readily as it might recognize materials which are part of its normal everyday economy, such as vitamins A and E? And that it then continues to manufacture its own antioxidants which work alongside the artificial ones to keep free radical activity low?

Weindruch and Walford's views
When animals are placed on dietary restriction programmes there seems to be a 'selective' improvement in levels of certain antioxidants and not of others. For example, no change is seen in levels of production of superoxide dismutase or glutathione peroxidase, two of our most potent free radical fighters, when restricted diets are followed. However, there is a significant increase in levels of catalase with dietary restriction, especially in the liver and kidneys, and interestingly one of the signs of ageing is a marked lessening of catalase activity in these organs. Weindruch and Walford have now clearly demonstrated that an average of 50 per cent improvement in catalase activity occurs during dietary restriction. They caution that, in their opinion, other systems and effects divorced from free radical activity theories are the main factors in ageing. However, it remains clear that dietary restriction influences important aspects of the body's ability to cope with free radicals, and it is hard to see how this cannot but be significant, bearing in mind the importance of the damage free radicals can cause.

In the section on strategies I give guidelines for modifying or preventing free radical activity. This will involve diet, supplementation of specific nutrients, moderation of lifestyle habits and exercise, as well as other methods such as chelation therapy which have been found to have marked and beneficial effects on free radical activity.

What about natural vitamins?
I said early in this chapter that supplementation of artificial antioxidants seems to offer cell protection and some life extension potential. I also mentioned that when some nutrients are supplemented, such as pro-vitamin A (beta carotene) the tissues may be induced to synthesize or produce lower levels of other antioxidants, thus leaving the overall level of free radical fighters much the same as before supplementation. There is, however, much evidence that disappointing results such as this are not universal, even when the supplemented vitamins and other nutrients are not synthetic.

Background
Professor B. Ames of the Department of Chemistry, University of California, Berkeley, has stated that there exists a growing amount of evidence which shows that ageing, cancer, heart disease and other degenerative diseases are mainly due damage caused to cells by lipid peroxidation, including their DNA (Science (1983 221:1256-64)). Such peroxidation is, as we know, caused by free radicals which in turn are generated by a variety of factors including dietary fats, heavy metals (lead, cadmium) radiation, heavy exercise, increased metabolic rate, infectious or inflammatory processes and others, including deficiencies of antioxidants.

As Elmer Cranton MD states Journal of Holistic Medicine (1984 6(1):6-31)): 'Research in senility, dementia, brain ischaemia, stroke, and spinal cord injury provides a wealth of evidence incriminating free radicals as a cause of nervous system disease, and also provides a rationale for treatment.' He points out that the central nervous system not only contains the highest concentrations of fat of any organ, but that in good health it also contains vitamin C in concentrations 100 times greater than that found in most other tissues and organs of the body.

The concentrations of antioxidants in our tissues is, along with the level of free radicals active in those tissues, a key determining factor of length of life (as well, of course, as the level of health). An important function of vitamin C is protection of the central nervous system from peroxidative damage caused by free radical activity on fatty tissues.

Can antioxidants in the diet increase protection from free radicals?

1. Dr E. Calebrese and colleagues examined the protective effect of vitamin E supplementation against exposure to ozone (commonly present in polluted air) which degrades to form hydrogen peroxide (bleach) one of the most potent of all free radical producers. In this study, 12 adult human volunteers were supplemented daily with 600iu of vitamin E for a month. Samples of their blood - taken before the study started, and after two weeks and then after four weeks of supplementation - were exposed to varying levels of ozone in order to test the amount of damage taking place to cells, with and without different degrees of supplemented vitamin E in the donors of the blood. When blood is exposed to ozone it forms a damage by-product called methaemoglobin. This byproduct was found in far lower levels during the second and fourth weeks of vitamin E supplementation, especially at the highest exposure to ozone.

2. Much research confirms that as red blood cells reach the end of their useful life (as they age in fact) 'markers' appear on their surface (called 'senescent cell antigens') which alert defense mechanism cells (immunoglobulin-G auto-antibodies) to target them for removal from the circulatory system. A study was conducted in which red blood cells taken from vitamin E deficient rats were examined in relation to this whole phenomenon. The results showed that vitamin E deficiency caused premature ageing of the red blood cells and that this led to binding with the cells of the antibodies. The cells of vitamin E deficient animals - of all ages - were seen to behave in the same way as the red blood cells of old animals on normal diets. The researchers said: 'Results of the experiments indicate that erythrocytes (red blood cells) from vitamin E deficient rats age prematurely, indicating that oxidation accelerates cellular ageing.'