The continual progress in the quality of health care in developed countries during this century has resulted in an ever-increasing expectation of life. However, the success of medical research, which includes successful diagnosis and treatment, has been achieved at considerable cost. This cost is largely due to the steady rise in age-associated disease in ageing populations. It has been said that in the U.S.A. the costs of medical treatment in the last month or two of life, very often significantly exceed that spent on the whole of the previous life of each patient. In developed countries as a whole, the cost of medical care for individuals over 65 is five or six times higher than for younger individuals, and about 50% of individuals over 65 have some physical disability. WHO statistics show that the costs of health care as a percentage of gross national product in these countries doubled between 1960 and 1986. The cost in real terms will double again early in the 21st century. Much of this expense will be due to the increasing costs of health care from the aged. In addition to medical expenses, general care of the aged consumes the activity of an army of nurses or other health care workers, as well that of many younger relatives.
All this makes depressing reading, and the list of age-associated diseases makes the overall picture even more gloomy. One of the commonest is cardiovascular disease, commonly known just as "heart disease". This is in fact not always a disease, but simply a result of ageing. The heart is a highly efficient pump, but it has limited capacity for repair, and with time it loses efficiency. This may be due to the calcification or other defects in the valves, a loss of muscular activity, or, most commonly, a failure of coronary arteries to provide blood and oxygen. Coronary arteries commonly become blocked through the formation of atherosclerotic plaques. Arteries lost elasticity through the age-related cross-linking of proteins such as collagen and elastin, and this results in a rise in blood pressure (hypertension) and increased risk of stroke from cerebral haemorrhage.
There is strong interdependence between the vascular and renal system. The kidneys receive 25% of cardiac output and about 1700 litres of blood are processed each day. The kidney is sensitive to hypertension, and has itself an active role in the control of blood pressure. Although the kidney is far less sensitive than the brain or heart to tissue damage, its components do lose efficiency with time.
Loss of kidney function is common in old age, and is not uncommon in younger individuals. Also, the regulation of the flow of urine is quite frequently lost in old people, which leads to the problems of incontinence.
Diabetes affects carbohydrate, fat and protein metabolism, primarily as a result of abnormally high glucose in blood and tissues (hypergly-caemia). There are two types of diabetes. Type 1 is early onset and is due to the failure of the pancreas to produce a sufficient quantity of insulin. It is treated by injections of insulin. Type II is less well defined and it is, characteristically, an age-related disease. It is due to abnormalities in insulin metabolism which are not fully understood. Its incidence is greatly increased by obesity. Although it can often be treated by a controlled diet, it is nevertheless a common debilitating disease amongst old people.
Osteoporosis is due to a loss of bone mass, and this commonly causes hip or other fractures in old people. It becomes particularly common in post-menopausal women, but also occurs in elderly men. The addition of calcium to the diet and greater exercise delay the symptoms, but it is nevertheless one of the commonest age-associated diseases. Osteoarthritis is caused by deterioration of the normal structure and function of joints, is frequently associated with painful inflammation. Part of the problem is simply due to the wear and tear of mechanical structures which cannot repair themselves, but autoimmune responses can also be important. This is a general problem in old age as the immune system loses efficiency and the ability to distinguish self from non-self proteins, components of proteins, or other molecules. The decline in the capacity of the immune system to combat invading pathogens can also have severe consequences for old people. It is well known that they become more susceptible to respiratory diseases such as influenza, bronchitis and phneumonia.
One of the most obvious age-related changes is the appearance of skin, particularly on the face and hands, or other exposed parts of the body. One of the major changes is due to the cross-linking and loss of organisation of collagen, which is a major structural component. Wound healing becomes slower during ageing, and in some cases the failure of skin ulcers to heal becomes an important problem. The effects of the ultraviolet components of sunlight are well known. Not only is wrinkling and the formation of "age spots" accelerated, but there is an increasing risk of skin cancer.
The majority of body cancers are known as carcinomas, and it is very well established that the incidence of these is age-related. There is good evidence that the progression of these tumours is a multistep process, so clearly the probability of the emergence of a malignant tumour is time-dependent, and therefore age-associated. The risk of malignancy begins to rise at the age of 50 or so, and thereafter increases steeply to an incidence of 30% or so at the age 80-85. After cardiovascular disease, cancer is the commonest cause of death.
Finally, there is deterioration of brain function with age. Strokes are due to a failure of blood supply to important parts of the brain, which soon suffers damage in the absence of oxygen. This can be due to haemorrhage, often caused by high blood pressure, or it can be due to blockage of an artery by a clot, or a detached atherosclerotic plaque. Neurons are steadily lost as we got older, and this affects memory and other brain functions. Accelerated damage or cell loss gives rise to Alzheimer's disease, which is premature senility. Obviously, the younger an individual is, the greater is the distress caused by Alzheimer's disease, but is the population as a whole, the incidence rises continuously with age, and few very old people are completely free of the symptoms. It is unfortunate that the brain is particularly sensitive to cell and tissue damage, and neurons can never be replaced. The retina is an extension of the brain, and it too suffers damage with ageing. This often leads to poor vision or blindness. Also, the long-lived proteins in the eye lens, become cross-linked, oxidised or have other changes with increasing age, so cataracts become increasingly common. The delicate mechanisms that are essential for hearing lose their efficiency with age, so poor-hearing or deafness becomes one of the commonest problems amongst the elderly.
This long list of age-associated diseases is indeed depressing, but as any physician will tell you, there are many other less well known age-associated diseases. It is not surprising that the overall increase in lifespan results in escalating costs of health care. One reason these health care costs rise is due to the continual development of new sophisticated equipment for diagnosis, and also for treatment. These tools are usually very expensive, but once their worth is established, every hospital has to have one.
In general, physicians are expected to treat each disease as it arises, irrespective of the age of the patient. Unfortunately, in the case of elderly patients, the successful treatment of one disease is all too often followed by the appearance of another. This is a major reason for the ever increasing expense of treating these patients. Whether we like it or not, the law of diminishing returns applies, and this raises serious ethical issues. In practice, a compromise has to be reached so that the younger a patient is, the more appropriate it is to use an expensive medical treatment.
One of the success stories in medical treatment, is the increasing use of surgical repair and replacement of parts. We have long been familiar with dental care, in which cavities in teeth are filled, abscesses can be treated by antibiotics, with or without tooth extraction, and false teeth can be provided as required. Comparable intervention in other parts of the body has been developed much more slowly. However, partially blocked coronary arteries are now commonly treated by bypass surgery, hip-joints are often replaced with mechanical substitutes and cataracts are replaced with implants. In addition, organ transplantation has become common, particularly kidney transplants, but also those of heart or liver. These treatments are expensive, and with regard to organ transplantation, there is an ongoing shortage of donors. Another problem is the need to prevent rejection of foreign tissue, so patients have to take drugs to suppress the immune system for the rest of their lives. This can, of course, have unwanted consequences or side effects.
The general medical strategy to replace more and more parts of the body is providing the maintenance that the body itself is unable to achieve. So in this sense, artificial maintenance is increasing lifespan. However, as a general strategy, it is running into formidable difficulties. One problem is the justification of the expense. At what age is it appropriate to adopt surgical intervention? This may depend on the financial resources of the health system itself, or the bank balance of the prospective patient. Obviously, fewer expensive operations are carried out in third world countries than in developed ones. This problem will not go away. Some surgeons believe that the problem of insufficient organ donors will be solved by xenotransplants, that is, the use of organs from animals. Pigs are commonly said to be the most suitable donor animal, because their size and physiology broadly matches that of humans. However, the rejection problem is much more severe with tissue from another species, so at present much research is in progress to circumvent in one way or another, the rejection of pig tissue. Another problem, rarely discussed, is that pigs have a relatively short lifepsan compared to other herbivores of comparable size. One could not expect a pig kidney or pig heart to last much more than a decade, so some surgeons talk about repeated or successive transplants. It is also a fact that transplant surgeons are very well paid for their experience and skills. This financial reward becomes a driving force in itself, particularly in the U.S.A., where many elderly patients are all too ready to pay large medical fees.
Other intervention procedures are often discussed, fuelled by the general hope that as research progresses, more and more difficult operations will be carried out. It is probably time to take a hard look at some of the more fanciful operations which have been aired. One set of future procedures is concerned with the central nervous system. At present severe damage to the spinal cord often leads to loss of limb function. Although, minor nerve can regenerate to some extent, major nerves do not. This has lead to much discussion of the possibility of nerve regeneration in the future. However, it is not only a question of stimulating the growth of new nervous tissue, there is also the even more important problem of the specificity of nerve connections. Successful repair of a spinal cord involves perfect matching and rejoining of the many thousands of severed nerve endings. The enormity of the problem can be best illustrated by a consideration of the likelihood of eye transplantation in the future. Every sensitive cell in the retina is connected to a corresponding cell or cells in a specific part of the brain, known as the visual cortex. All these nerve connections, or axons, pass along the optic nerve, and there are about a million of them. After cutting the optic nerve in an eye transplant operation, all these specific axon endings must be rejoined. It is not just a question of simple regeneration or repair, but of one where complete specificity between retina and brain is retained. At present, it is not even understood how such specificity is laid down in the early development of the eye. (Although some preliminary understanding has come from the study of experimental animals, such as the toad Xenopus, which has much greater powers of nerve regeneration than mammals have). This is an area where science fiction enters the province of real medical or biological science.
The problems of medical treatment are not just associated with advances in surgery, or other examples of high-technology medicine. Let us consider again the list of age-associated diseases. At present, considerable resources are being devoted to research on everyone of these in laboratories all round the world. There are specialised clinical and non-clinical research scientists studying heart disease, diabetes, osteoporosis, Alzheimer's disease, cancer, and so on and so on. There are specialised journals which publish the results obtained. There are national and international conferences, where experts in each disease exchange the latest information. There are huge pharmaceutical companies competing with each other, often carrying out their own classified research, with the aim of finding new drugs for better treatments. The aims of all this research are well known, first, to find better treatments of each disease; second, to prevent or delay the onset of the disease, and third, to understand why the disease arises in the first place. These aims are completely laudable, and everyone would wish success for the research teams involved. What is unfortunate is that those studying one disease, for example, late-onset diabetes, do not communicate with those studying another age-related disease, such as cancer. Those working on cardiovascular disease do not talk to those studying osteoporosis, and so on. The study of each disease is at present regarded as a complete discipline in its own right.
The truth is that the second and third aims of the research, that is, the need to understand the origin of each disease, and the need to devise means of prevention or delay, should be within the province of ageing research itself. We saw in earlier chapters that the physiology and anatomy of the body is designed for finite, not infinite, survival. We also saw that maintenance of body functions comprises a set of mechanisms, which taken together use a considerable proportion of body resources. Maintenance is never perfect, so defects arise in individual components of cells, in DNA, in proteins, in membranes, and so on. These defects in cells also affect tissue and organ function in all parts of the body. Although at the tissue and organ level ageing may have multiple causes, at the cellular level there are common features to do with the types of damage or imperfection that can arise in the molecular components which are common to all cells. Thus, there are changes in proteins, such as cross-linking, which may have important deleterious effects in arteries, in the brain, in the lens, in joints and skin, and so on. Therefore all those scientists studying degenerative age-related diseases should not only have a real interest in those fundamental molecular changes, but they should also share and exchange information about the origin of all the different diseases. In a word, they should be interested in ageing per se. This is certainly not the case at the present time. Moreover, the amount of resources devoted to research on ageing, especially in Europe, is quite small. Ageing is all too often side-lined as a pseudo-scientific field, together with the belief that those working in it are only trying to increase the maximum lifespan. The truth is that all those scientists studying age-associated disease are themselves studying ageing, even though they may be unaware of this.
Unfortunately there is little sign that the general message is getting through to the medical community. In 1942 the geratrician Edward Stieglitz wrote an article on "The social urgency of research on ageing". The following passage is particularly apposite:
The shifting age distribution of the population with its increasing proportion of those in the older age groups has introduced innumerable problems of the most practical and significant character. The situation is without precedent. The millions of elderly are here. There will be more. Many are well and capable of continued productive and creative effort if given opportunity to work within their capacities. Others, and there are many, are prematurely disabled by the insidious chronic and progressive disorders so frequent during the senescent period and become heavy burdens upon the family and society by reason of the long course of their disablement. Gerontology, the science of ageing, is divided into three major categories: (a) the problems of the biology of senescence, (b) the clinical problems of ageing man, and (c) the socio-economic problems of ageing mankind. These three categories are intimately and inseparably related; progress in one field us dependent upon progress in the others and vice versa. Clinical medicine, in its youngest speciality, geriatrics, can do much to solve the most distressing problems in the social field. To name but two potential contributions of vital importance: Personal preventive medicine may greatly reduce the toll of premature disability and bettered diagnostic methods can more clearly define the limitations which go with normal ageing. Yet even more intimate is the dependence of clinical medicine upon advances in the fundamental sciences in elucidating just what ageing is, what it does, what retards or accelerates it and why. It cannot be over-emphasized that the more we know about the biologic mechanisms of the ageing processes, the more effectively can clinical medicine treat the ageing and the aged (italics added).
If this was the case more than 60 years ago, it is even more true and relevant today. This is the doctors' dilemma. They are trained to treat each disease as it arises as best they can. The general physician has a broad knowledge, who refers patients to specialists with detailed knowledge of a particular disease. These consultants read the appropriate literature to keep up with current research in that particular field. The whole medical scene has become compartmentalised, and every group of specialised physicians is promoting its own interests, including the provision of expensive equipment. This is the situation which leads to escalating health costs, especially in developed countries, and to costs that certainly cannot be afforded in developing countries. Instead of developing more and more expensive treatments for age-associated diseases, the emphasis needs to be altered
Major age-associated pathologies
Cardiovascular disease Cerebrovascular disease (stroke) Dementias Cancers
Late onset diabetes Kidney failure Osteoarthritis Osteoporosis Cataracts and retinopathy Loss of hearing
Some non-pathological changes during ageing
Wrinkling and sagging of skin
Whitening of hair
Loss of muscle strength
Development of pigmented age-spots
Loss of lens accomodation
Incontinence so that more consideration is given to prevention of disease. And to be successful in prevention, one needs to know in detail the reasons for the origin of each disease. Intervention at this stage not only saves money, but also improves the quality of life of old people, a theme which will be explored in the next chapter.
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