Professor Hayflick of the University of California, San Francisco, showed in the early 1960s that cells (he was using human connective tissue cells) in a laboratory dish, which were kept well-nourished and at optimum temperatures and conditions, would continue to divide up to around 50 times, after which they would start to die. When cells from older people were taken and treated in the same way they divided fewer times compared with embryonic cells, which when cultured divided more often. In all cases, whether the cells came from embryos or middle-aged or old people, they always reached a point in time when for no apparent reason their ability to divide and reproduce themselves declined, and they ultimately died.

What does a cell do while it is functioning?
Most of our body cells have unique and specific tasks to perform. They are not unlike integrated factories in which a constant supply of raw materials is delivered, entering via the cell membrane (factory gate) which keeps out what is undesirable and lets in (and out) what is needed, including fatty acids and glucose for energy production (fuel). Fuel for energy is essential so that a wide array of different substances can be manufactured, which will then be used or stored by the body, including proteins for the repair or building of tissues, energy storage molecules such as polysaccharides, and various fats and information storage units deoxyribonucleic acid and ribonucleic acid (DNA and RNA).

In order for the manufacture to take place accurately and efficiently a number of protein catalysts are essential at each stage of manufacture (catalysts are substances which take part in chemical processes but which are not themselves used up by the process). It is known that up to 200 million protein molecules, some used as catalysts, others in the structural creation of new molecules, are involved in this whole process, and exist together inside each cell. Each and every one of these proteins will have been encoded with their particular characteristics, uses and functions by DNA (genetic instruction and information messages).

Since proteins are made up of collections of building blocks called amino acids, the unique structure and attributes of each protein is decided by which of the twenty or so amino acids they contain~and the order in which these 'building blocks' are assembled. Each protein has different quantities and ratios to those found in another protein. This is why kidney cells are not me same as blood cells, and why brain tissue is not the same as skin. All are protein-based but each is different, and it is the DNA encoding which tells the cells which amino acids and what ratios and quantities of these to assemble in order to create that individuality.

This whole protein manufacturing process is carried out in the cytoplasm of the cell while the DNA is kept safely tucked away in the nucleus of the cell. So, whenever a new protein is required (a constant process) for use as a structural unit in the tissue of an organ or part of the body, it is necessary to send instructional blueprints from the nucleus DNA (the master copy) to the cytoplasm (from the central office to the factory floor so to speak). This is achieved by sending copies of that part of the DNA which is required, from the nucleus to the cytoplasm, as a plan containing separate instruction information on RNA (ribonucleic acid) molecules. This messenger RNA then acts as a blueprint/template from which the new protein is designed and manufactured in a unit of RNA/protein called a ribosome (just like a specific machine tool).

Hazards
While all this is going on it is possible for a variety of reasons for damage to occur to the cell membrane, to aspects of the cytoplasm or to the essential DNA controls. This is because while all the industrious activity is continuing round the dock, a variety of hostile factors are also present, including changes m temperature, radiation damage, free radical activity (a normal byproduct of oxygen metabolism), possible bacterial and viral assault, nutritional deficits, toxic accumulation and a host of as yet unknown hazards including the possible influence of the mind (negative emotions, poor stress coping etc.) on defensive and repair capabilities. Thus the factory in which protein is being manufactured also has a need for an efficient waste disposal system and a well-organized maintenance crew and fire brigade. In good health it has all of these in abundance.

These homoeostatic (self-regulating) functions are provided by a host of different enzymes and antioxidant substances which act to protect against toxicity and to deactivate free radical activity and repair damaged tissues, including DNA, when this is necessary. However, under adverse conditions the maintenance crew (enzymes mainly) and fire brigade (antioxidant and enzymes) can themselves be damaged and compromised and therefore become inefficient in their repair and defense functions.

This could well be the case where a diet and/or lifestyle provides an excessive quantity of free radical activity, such as derives from a diet high in fats and sugars, or an intake of excessive alcohol, tobacco smoke, environmental pollutants etc., especially when such exposure is also combined with a diet poorly supplied with anti oxidants such as are found in fresh fruits and vegetables - vitamins A, C, E etc.

Energy
All of our cells' manufacturing and defensive functions including the copying onto RNA from DNA of the master plan, the sending of the RNA to the cytoplasm and the assembly and manufacture of the new protein, requires energy, and this is constantly being provided in cells by use (burning) of fats and sugars. In the cytoplasm of our cells lie a host of miniature energy production sites called mitochondria. These bum food (fats etc.) in the presence of oxygen in order to meet the energy needs of the cell. In the manufacturing process by-products called free radicals are formed. These have the potential for causing damage unless rapidly 'switched off' or 'quenched' by antioxidant nutrients (Vitamins A, C and E) or enyzmes (such as super oxide dismutase).

The rate at which our cells operate and use energy determines what is called our basic metabolic rate (BMR) which seems to be a major feature in understanding ageing processes, since slow BMRs are associated with longer life and speedy BMRs with shorter life expectancy. The BMR to a large extent decides our core temperature, another feature of life expectancy (low core temperature = longer life expectancy) and this is itself influenced by features such as hormonal balance. I will explain this more thoroughly in later chapters.

Problems
If there are problems in the nucleus of a cell due to damaged DNA, or if energy levels are poor and transportation of RNA or raw materials becomes sluggish, or if anything at all goes wrong in the protein synthesis (manufacturing) process, or should the cell membrane become inefficient in selectively allowing the passage of only desirable substances, then the cell will become inefficient, and start producing faulty material. It might also become unable to cleanse, repair and reproduce itself and would then ultimately perish.

The alterations which are seen in cells, as this array of changes occur, were outlined in the previous chapter, and are listed here once more, since they represent the very center of our search for the processes which have to be slowed or reversed if we are to achieve life extension.

These changes are dominated by the slow build-up in cells of 'altered proteins' which result in all or some of the following states:

1. Build up of age pigments (lipofuscin). The presence of these fat/protein granules (found in nerve and muscle cells) is largely the result of the loss of the ability to normalize cross-linkage of proteins and fats following free radical activity.

2. Enzymes which have changed in their sensitivity to heat and their functional ability to act as catalysts in various cellular activities.

3. Enzymes which behave poorly in their defensive roles as part of our immune function.

4. Plaque and tangles of tissue found in aged brain tissue (e.g. in Alzheimer's disease).

As well as these accumulating deposits and changes there seems, with ageing, to be a tendency for both the quality and rate of protein synthesis to become increasingly disturbed. Whether these alterations are the result of a gradual loss of efficiency in dealing with the hazards of life, or whether they are the result of a built-in (genetically programmed) decline feature, remains a major question for research. What is known for certain is that where the efficiency of cell detoxification and DNA repair is operating at its best there is a coincidental increase in life expectancy.

These factors, therefore, lie at the heart of our search for an understanding of how to increase our normal life span, and they involve some of the problems and processes, on a cellular level, which are thought to play a large part in the ageing process.

If we accept a 'wear-and-tear' theory of ageing it seems to be the likely outcome of a gradual overwhelming of the efficient conduct of cells, as they start to work less productively, accumulating more toxic debris, slowing down in their energy production and generally failing to protect and repair themselves in the face of a combination of undernutrition and toxicity (in its widest sense) including free radical activity . . . unless there is another factor, which most of us would recognize in relation to modern manufacturing techniques: built-in obsolescence.

Built-in obsolescence?
Cars and refrigerators have a time-span of normal use which the manufacturers estimate to be so many years, after which time they become uneconomical to repair. You then have to buy a new one. It is considered possible by many experts that just such a feature has been built into our DNA. That a genetic code exists which says, at a given point in time, 'Enough, it's time to go.' It may also be the case that this 'switching off' decision, if it is genetically programmed, is only activated once a certain level of toxicity and inefficiency is reached, at which time the organism somehow recognizes a point of no return a moment to give up the struggle.

Strategies
As indicated in Chapter 1, the best results to date in extending life experimentally have been achieved by dietary manipulation, using either individually or in combination:

1. A degree of calorie restriction, or
2. Antioxidant nutrition (this quenches free radical activity).
3. Use of amino-acid substances to trigger growth-hormone production.

What is fascinating to those involved in nutritional medicine is the fact that similar strategies (1 and 2) including dietary restriction such as periodical fasting, together with an antioxidant (fruits/vegetables etc.) rich diet, have for years been effectively used to treat many chronic diseases and ailments associated with ageing, without particular emphasis (or even awareness) of their possible application to life extension as such.

Thus we have traditional naturopathic medicine (which employs mainly nutritional and fasting techniques as well as lifestyle modification) appearing to be the most experienced branch of healing in applying the very techniques which are advocated by orthodox research findings for the promotion of life extension.

Before examining aspects of the effects on life extension in animals, of numerous dietary restriction studies, we should briefly look at some of the results of work in the field of fasting and dietary restriction which has involved humans and animals in the treatment and prevention of disease. In examining this evidence you will have the chance to glimpse some of the ways in which we can use the knowledge gained from animal studies in our own situations, by modifying them towards what is practical and safe in everyday life.

As physiologist Dr Edward Masoro, of the University of Texas, San Antonio, states: 'Once we learn how dietary restriction works, we'll get clues for intervention that are more palatable than partially fasting for a lifetime.' (Newsweek, 5 March 1990, page 37).

I hope the evidence in the next chapter will convince you that there are already ways which are both palatable and effective.