The Aging Processes

How long should we live? An accepted formula for calculating this, in mammals, is based on the multiplication by five of the time it takes the skeleton to mature. Thus because a dog’s growing period is three years, its life span average is considered to be fifteen years. Human skeletal growth is complete by age 25 and so a fair estimate of our life expectancy is around 120 to 125 years. Anyone failing to get close to this is losing a good number of potentially happy and productive years.

If, then, our natural ceiling is about 120 years, beyond which human life is unlikely, we should ask why so few of us come anywhere near that age, and why those who do are usually in an advanced state of decrepitude. Infirmity and disability are not attractive prospects, so why should the aim of a longer life be an attractive idea? Simply because it is not the aim of those promoting life extension to help us towards that 120 year barrier in anything other than a reasonable state of well-being.

Professor Leonard Hayflick of the University of California, San Francisco, is quoted as calling this search ‘the last great biological frontier’ (‘The Fountain of Youth’, Newsweek, 5 March 1990, page 34). In fact the quest has been summed up quite neatly by another Californian, Professor Edward Schneider (University of Southern California) for it was he who said ‘We are trying to add life to years rather than years to life.’

In fact both aims are synonymous and should be equally vigorously pursued, for if quality of life, including vitality, vigour and lack of chronic disease could be achieved, it is almost certain that life expectancy would increase.

Expect to live longer by living longer

Any boy born in the US or UK in 1990 can expect to live just over 76 years, while a girl can look forward to 83 years of life.

The older you get the longer your life expectancy becomes. For example, if you are now 25 your life expectancy at birth was 72.7 if you are male and 80.6 if you are female. However, your life expectancy now is 76.2 years (male) and 83.1 (female). Since birth your life expectancy has increased by 2 to 3 years. This increase in life expectancy is even more dramatic for people who are now older than 25, as follows:

The longer you stay alive the longer you can expect to live, seems to be the message. But not even the longest of these ‘expectancies’ approaches our true biological potential, and life extension methods are aimed at redressing that shortfall, rather than actually altering the ground-rules.

The immediate prospect of living to well over 100 may not be attractive, especially if you hold the idea of advanced age alongside an image of physical and mental decline. However, Prolonged life would be a much more attractive prospect were it linked to an almost assured state of mental and physical wellbeing and fitness. This is the aim of natural life extension. Long life is not just seen as an end in itself, but rather has as its objective a state of excellence in health which will bring enjoyment to long life.

In fact, the two aims (health and long life) are inseparable since the only methods of life extension so far researched and proved to work (namely methods of calorie restriction within a framework of a diet providing all other essential nutrients, as described in detail in later chapters) have shown that with an extension of life come major health benefits in terms of lower incidence of the diseases we normally associate with age, as well as the disappearance of many of those ailments that already exist when the programmes are begun.

While the ageing process quite obviously takes place with the progression of time, it is not necessarily directly linked to it. People can and do age at different rates and, in some instances (Down’s Syndrome is an example) ageing can be seen to speed up and sometimes become extremely rapid. The study of ageing has led to the development of a variety of theories to explain the ‘why’ of the process, since the ‘what’ is all too clear. All or some of the mechanisms described in the different theories may be involved in ageing in any given instance.

Some experts prefer to use the expression ‘failure to survive’ rather than ‘ageing’, since this word has overtones of an inevitable decline and degeneration, which some believe to be inaccurate. The two main lines of investigation into the ageing process focus on either those cellular changes which might be involved, or on the whole organism and the changes which occur in it. As Alan Hipkiss and Alan Bittles state in their contribution to Human Ageing and Later Life (edited by Anthony Warnes and published by Edward Arnold, London, 1989): ‘It is accepted by most biologists that ageing ultimately has a molecular basis and that, whatever the changes in molecular structures or functions which accompany or cause ageing, these changes are manifested by deleterious alterations in cellular, organ and organismic behavior.’

What we’ve got to look at, then, is not just what is happening in the basic cells which make up the whole, but also at the whole organism and how changes which have occurred in it (for whatever reason) influence its totality, including its cellular function.

Cellular theories

There have been many ideas put forward on cellular ageing. One is that a variety of errors and changes in our genetic information control mechanism (deoxyribonucleic acid or DNA) contained in every cell of our bodies take place with ageing, resulting in either mutation or damage to cells. This then leads to inadequate (both in quality and quantity) protein manufacture with an inevitable decline in function, since continuous synthesis of protein is essential for repair and maintenance of our multitude of organs and parts.

Free radicals (toxic by-products of oxygen metabolism) are also pinpointed as havoc producers at a cellular level, and these are thought to lead to the sort of damage to our cellular information storage (DNA) described above, or alternatively to an impairment of the energy status of cells and a consequent malfunction in detoxification activity and other functions. Free radical activity induces proteins and fats to combine to produce age-pigments called lipofuscin (‘liver spots’) which overload cells reducing their efficient working.

The development of cross-links between cells as a result of faulty enzyme activity, free radical activity or sugar-related alterations (known as glycosylization) are also thought to lead to age-related changes (wrinkles are a superficial example). Cross linking of this sort is often associated with poor protein synthesis. Connective tissue (collagen) which supports and gives shape and cohesion to other soft tissues is commonly affected by cross linkage associated with ageing. It is thought by some researchers that ageing is a preprogrammed process, and that just as we grow and develop at a certain rate so do we age at a certain rate, with the whole process determined by genetic factors (DNA again).

So the cellular theories of ageing seem to focus on the faults which arise when, for one reason or another (free radical activity, or a built-in slowdown, or the onset of cellular mutation) cells become less able to repair, energize and detoxify themselves, causing alterations such as cross-linkage. Thus cells generally start to function at an increasingly poor level, and under certain circumstances start to mutate into cancerous forms.

Here are some of the theories which have been developed to describe the causes of ageing of the whole organism.

The simple wear-and-tear theory holds that we age as our non replaceable parts slowly wear out. This begs the question ‘why’ the wear-and-tear takes place, the causes of which lead us back to what is happening on a cellular level, possibly to free radical activity, cross-linkage of cells, inadequate protein synthesis, and accumulation of undesirable material in cells and tissues. Another facet of this same basic concept lays the blame for ageing on a combination of the accumulation of toxic debris (as our detoxification processes become less efficient) and the slow exhaustion of non-replaceable substances. The toxic build-up again describes a process without ascribing a cause, unless substance exhaustion is that cause.

The process of ageing is seen by some to be a result of hormonal and/or immune function changes. Once again we are asked to accept an effect as a cause. While hormonal disturbance can undoubtedly lead to a speeding up of ageing, in itself hormonal disturbance has to have a cause, and this may once more take us back to disturbance at the cellular and molecular levels.

These ‘whole organism’ concepts therefore seem to be seeing the process of ageing as part of the cause of ageing. It seems more probable that once cellular changes have become advanced (for whatever reason) and the consequent processes of ‘wear-andtear’ or hormonal/nervous system changes have started to become marked, that the process of decline becomes self perpetuating.

As I will show in the last chapter, some life extension methods aim specifically at restoring balance to imbalanced states which are a common feature of ageing, such as the slow build-up of excessive levels of vital substances such as serotonin and of the enzyme monoamine oxidize (MOA). Such methods often do influence the local imbalance but almost always fail to correct underlying trends. At such a stage, unless something is done to intervene and restore a degree of competence to what is faulty and malfunctioning at the cellular/molecular level, such as detoxification processes, protein synthesis etc., any organ dysfunction (liver, heart etc.) which has resulted from the cellular problems, itself becomes a ‘further cause of ageing’. Comprehensive approaches, such as are offered by a calorie restriction diet seem able to improve (or retard) all (or most) levels of this vicious circle of decline, rather than just elements of it.

Integrated theories

To the credit of some experts in the field there have been many attempts to integrate elements of the theories listed above. This has led to the sort of scenario in which (for example) free radical damage to DNA is seen to result in altered nervous system and hormonal functioning and a consequent speeding up of the ageing process. Or, the involvement of negative changes (for whatever combination of cellular or disease-caused reasons) of the nervous system and the hormonal systems (neuroendocrine system) might be seen to severely compromise the immune (repair and defense) functions of the body, thus hastening aging

It is in the integrated concepts of cellular and organ-related changes that a truly manageable understanding of the ageing process becomes possible. John Mann, writing in his book Secrets of Life Extension (Harbor, San Francisco, 1980) describes some of the ‘integrated theory’ thinking of a number of researchers. He discusses the work of Howard Curtis of Brookhaven National Laboratory who held that there was a ‘composite theory of ageing’, in which factors such as radiation, mutation and toxic accumulation all worked together to hasten the speed of degeneration.

He also says that:

In their ‘integrated theory of ageing’, Carpenter and Loynd explain how interactions of stress, metabolic waste production, free radical build-up, and somatic mutations work together to accelerate the rate of cross-linkage and other molecular changes that immobilize many of the body’s active molecules.

He continues by describing Hans Kugler’s ‘combination theory of ageing, in which several contenders appear together as causes of this process. These stress factors are seen to be problems which could at one time have been adequately dealt with by the body, but which, in combination, become overwhelming and thus accelerate the ageing process.

So, whether we are looking at integrated, composite or combination theories we seem to be seeing the same thoughts emerging; that a number of the cellular-change patterns lead on to organ dysfunction and a collapse of the body’s ability to deal with the continuing onslaught.

Newsweek magazine journalists Sharon Begley and Mary Hager (‘Fountain of Youth’, 5 March 1990) summarize the varying theories thus:

The first [theory] holds that the changes that accompany aging
are the inevitable result of life itself. DNA, the molecule of
heredity, occasionally makes mistakes as it goes about its
business of synthesizing proteins; metabolism produces toxic
avengers (free radicals) that turn lipids in our cells rancid and
protein rusty. This damage accumulates until the organism
falls apart like an old jalopy . . .

The other theory argues that aging is genetic; programmed
into the organism like puberty. There is evidence for both sides.

In fact, since we know that all sorts of outside factors influence life expectancy, it has become increasingly clear that both theories are correct and that it is on the underlying, genetically predetermined, maximum life expectancy (say 120 years in humans) that the multiple forces of toxicity, energy, infection, nutritional deficiencies or excellence, stress factors etc. are acting, and that it is to these areas that we need to address our attention in order that the potential life span might be approached, in a good state of health. I will show in great detail that it is possible to beneficially influence life expectancy in animals and humans by means of dietary manipulation, and the effects of this are to first improve health and only second to allow a longer life to emerge, not the other way around as so many research scientists seem to imagine.

This is because, unlike the rusting jalopy of the Newsweek analogy, we have something which no automobile has – a self-adjusting, self-repairing, self-healing potential called homoeostasis working for us – and it is dietary manipulation which can trigger its efficiency when it is doing its job in an unsatisfactory way.

Altered proteins

In the next chapter I describe the complex, hard-working and often dangerous life of a typical cell, indicating some of the amazing qualities and properties it possesses as it performs its multitude of tasks in the face of a remarkable array of hazards. It is important to understand the effect of these hazards (e.g. free radical activity) and to realize that the changes which result from them are the commonest age-associated features which can be identified at the cellular level. These changes are dominated by the gradual accumulation in cells of what are called ‘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 a result of the loss of the ability to normalize cross-linkage of such molecules following free radical activity.
   

   
   

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

   
   

3. Enzymes which behave poorly in their defensive roles as part of 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, 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 encoded and therefore programmed) decline feature, remains a main question for research. The results of such research will probably show that they are both operating and that it is the hazards of life which we can most easily influence, although doubtless genetic engineering will eventually allow for tinkering with the coded DNA messages which set the current human limit of life at around 120 years.

The genetic argument

Some scientists believe that as the processes (listed above) get underway – whether due to free radical activity, enzyme inefficiency or anything else – a genetic process of ageing is triggered. It is as though there are encoded messages in our DNA just waiting for this stimulus in order to start acting, and of course the time of life at which this begins will relate directly to how efficient the individual’s body is in dealing with free radicals and with producing active enzymes, and generally coping with the vicissitudes of life.

In simplistic terms, then, this argument says that the healthier you are, the longer it will be before your genetic ageing factors, are triggered, and therefore the longer you will live. It is a clear example of survival of the fittest, with those of us with the most problems (whether genetically inherited or acquired through inadequate lifestyle and nutritional imbalances) dying younger than those with ‘good’ genes for life expectancy and more health promoting lifestyles and diets. It seems highly probable that those animals which live longer on dietary restriction programmes are not exceeding their allotted genetic life spans. Rather it is those who fail to live as long as these dietary restriction animals which are over-eating themselves into early old-age.

Werner’s syndrome

In human experience there is evidence for a genetic ageing gene, and this is seen in the condition known as Werner’s syndrome. This occurs in about one in a million children and causes rapid ageing, so that by the early advanced ageing is seen, and few live to reach 40 years of age. All the diseases associated with age, degenerative and malignant conditions are common in Werner’s syndrome. When the cells of these people are examined they are found to continue to divide in laboratory dishes no more than between 10 and 20 times before dying, unlike normal human cells which continue dividing up to 50 times. Identifying which genes are involved in this condition is one quest of those scientists who see life expectancy enhancement to come from manipulation of inherited characteristics.

The search for evidence of a genetic control of ageing has led to experiments involving insects such as flies. At the University of California, Irvine, flies have been bred which are themselves not allowed to breed until they are at an advanced (for them) age of 70 days. After between six and ten generations the offspring of these long-lived flies are found to be living 40 per cent longer than their normal expected span. These flies are also found to be healthier and more vigorous, as well as being better able to cope with stress factors than ‘normal’ flies. The genes so far identified as being involved relate to the insects’ metabolic rate (how fast the organism ‘burns’ fuel) and this, as is explained in the next chapter, is a key area of interest for those examining life extension.

Whether this line of research into genetic control of ageing will yield satisfactory, readily available, methods remains for the future.

Do-it-yourself anti-ageing approach

For the present there are already techniques, mainly involving dietary manipulation, which can safely lead to better health and greater efficiency, and, therefore almost certainly, to an increase in life span. It is hard otherwise to imagine why leading researchers into ageing are applying dietary restriction to themselves. For example, at the National Toxicology Laboratory, Little Rock, Arkansas (where around 20,000 happy rats are kept on a dietary restriction programmed, doubling their average life span) the majority of the research team are so convinced of the value of this approach that they are collectively eating in a reduced fashion themselves.

Newsweek (5 March 1990) reports that Dr Roy Walford, of UCLA, has for some four years eaten to a pattern of 1,600 calories daily (compared with the more usual 2,500). His findings with animals have certainly convinced him that whatever the genetic encoding which might one day be unravelled, starting now with a sure-fire approach to health is going to produce advantages.

What research has shown for certain is that where the efficiency of cell detoxification and DNA repair is best, there is coincidental increase in life expectancy, and the approach ofdietary restriction is the safest way we know which can lead tothis. This strategy, therefore, lies at the very heart of our quest to increase our life span.