Robin Holliday

Gerontology is the scientific study of ageing. It is widely believed by those outside this field, and by some within it, that the ultimate aim of gerontology is to increase the human life span. 1 argue here that there are other much more cogent reasons for the pursuit of research on ageing.

Life span can be defined either as the expectation of life after birth in any given population, or the maximum achieved by any one individual. The expectation of human life span has been steadily increasing throughout this cen- tury in countries with good health care. This is the result of improved hygiene, immunization and the successful treat- ment of disease. We can conclude that biomedical research, in the broadest sense, has been very successful in increasing average life span. This success has nothing to do with the study of gerontology. Moreover, it can also be said that some medical practices are directed towards the prolongation of individual life span, most obviously by organ transplantation.

All this progress in health care has been achieved at a cost. Many diseases are associated with age, so increased life expectancy increases the likelihood of individuals con- tracting one or another of these diseases. As a result, the health care budgets have been steadily increasing in devel- oped countries. For example, the cost of health care as a percentage of gross national product in developed countries doubled between 1960 and 1986(’), and it is set to double again in the first or second decade of the next century. This rate of increase cannot be sustained indefinitely. Already we see the strain of rising health care costs on the National Health Service in the UK. The amount spent per capita is significantly greater in the USA, even though many do not benefit from the best health care. Comparable problems exist, or will soon exist, in many West European countries, Japan, Australasia and Canada.

The age-associated diseases I referred to include cardio- vascular and cerebrovascular disease, cancer, late onset diabetes, osteoarthritis and osteoporosis, senile dementias (especially Alzheimer’s disease), loss of renal function, retinopathy, cataracts and deafness. Clinicians frequently make a distinction between age-related disease and so- called ‘natural ageing’. Disease must be treated by appro- priate procedures, but ageing takes its own course. The dis- tinction is largely, if not entirely, false. The basis for this assertion comes from the study of gerontology itself.

A remarkable feature of mammalian ageing is the fact that different organ systems decline in function with a degree of synchrony. Thus, loss of cells in the brain accom- pany skin changes, which accompany lessened cardiovas-

cular efficiency, lowered muscular strength, and so on. This means that the causes of ageing are multiple, or mutifactor- ia1(2x3). It is obvious that the cross-linking of collagen, which increases throughout life, is different from the loss of neu- rones in the brain, or the progressive alteration of crystallin in the lens, or the accumulation of lipofuscin in various locations. Ageing can be said to be due to the eventual fail- ure of maintenance mechanisms, which sustain homeosta- sis and normal health for a considerable part of the adult lifespad3). There are at least ten prominent maintenance mechanisms, including DNA repair, the immune system, defences against oxygen free radicals, breakdown of defec- tive proteins, wound healing and detoxification. The study of all these processes encompasses a large proportion of the whole of biology. This research is not part of gerontology, but the eventual failure of these mechanisms certainly is. It must be stressed, however, that to understand the reasons for the failure of a maintenance mechanism during ageing, one must first understand the normal mechanism.

This may be fairly obvious, but what is less obvious is that the study of the pathology of age-associated disease in ani- mals and man is itself part of gerontology. There is a vast biomedical literature detailing the pathological changes which occur in cells, tissues and organs in each of the dis- eases I mentioned, as well as many others which are less well known. Oddly, most books on gerontology do not acknowledge the importance of this vast body of knowledge in advancing our understanding of ageing.

We can now see the source of the problem of expensive health care for populations with an ever increasing life span. Research on all disease is ongoing, and that research even- tually finds its application in clinical treatment. Thus, the clinician confronted with a given disease in an elderly indi- vidual makes use of the information available and applies the best treatment. This is the situation that cannot continue indefinitely.

The basic problem is that the strategy of biomedical research on diseases of the elderly is seriously flawed. It is not that resources on a worldwide scale are inadequate, the problem is the way these resources are used. What are the aims of research on age-associated diseases? They are three: (1) a better understanding of the aetiology or cause of the disease in question; (2) the development of procedures to prevent or delay the onset of the disease; and (3) better treatment of each disease as it arises. On the face of it, these aims are entirely laudable. However, the problem is that each particular disease is being studied independently of the others. There are whole institutes researching

specific diseases (cancer, heart disease and so on), there are international and national conferences devoted to them, there are specialised journals documenting the latest results of research. However, amongst all this activity, specialists in a particular age-related disease such as late onset diabetes, do not communicate, nor seem to wish to communicate, with those working, for example, on Alzheimer’s disease. And the latter do not communicate with those working on molecular and biological mechanisms of cancer, heart disease and so on. All these experts have exhaustive knowledge of their own field, but they are too specialised and may know and care little about other age- related diseases.

Of the three aims of biomedical research listed above, the first two are certainly within the province of gerontology, the scientific study of the processes of ageing. Thus, if we want to know the aetiology of an age-related disease, we need to study ageing itself. We need to study the cellular and mol- ecular changes which precede the overt onset of any partic- ular deleterious disease. Thus, the study of gerontology must have a central position in biomedical research. It must be related to the specialised research on age-related dis- ease, and it must also be related to the study of the mainte- nance mechanisms which are so necessary for normal health. Obviously, gerontology itself can be muti-discipli- nary, but most of those studying a particular area, for exam- ple the accumulation of changes in DNA with age, must also be aware of other age-related changes. Most important, sci- entists studying ageing, should regularly communicate with each other at conferences, in journals and in collaborative research. The problem is that gerontology itself receives little support, especially in Europe and Australia. In compar- ison to the sums spent on individual age-related disease, the funds made available for research on ageing are minus- cule. It is also unfortunate that many research scientists fre- quently regard gerontology as a somewhat ill-defined pseudo-science, and often assume that those interested in studying ageing are trying to extend the human life span.

In conclusion, various changes must occur if the problem of escalating health care costs is to be avoided. Firstly, there must be recognition, especially in clinical circles, of the cen- tral importance of gerontology for an overall understanding of age-related disease. Secondly, there must be recognition that much of modern cell biology, genetics and molecular biology is related in one way or another to cell and tissue

homeostasis and maintenance, and therefore also relates to ageing. Thirdly, there should be greatly increased finan- cial support for fundamental studies on ageing in universi- ties and research institutes. Fourthly, there should be many more courses on ageing in universities, with explanation of its central importance in biology and medicine. In edu- cational programmes, it would be very important to expose the myth that the aim of research on ageing is to increase the natural human life span. Finally, there should be a for- ward-looking assessment of very expensive treatments of diseases in the elderly. It is often assumed that more and more organ transplants, or other replacement of parts, will occur in the future. This is fully justified for younger mem- bers of society, but application of such treatment to the elderly and infirm is not only very expensive (all too often for the financial benefit of physicians), but is also an example of the law of diminishing returns. As every clinician knows, successful treatment of one condition in an elderly person is often followed quite soon by other problems.

These proposals, if implemented, would promote the first two aims of research on age-associated disease, namely to understand the aetiology of the disease in question and to devise measures to prevent or delay the onset of these dis- eases. The first major consequence would be a significant reduction in the costs of health care for the elderly, and therefore a means of curbing the ever-increasing health budget in developed countries. The second consequence would be a very significant improvement in the quality of life of the elderly. This would in turn have a third consequence, namely a reduction in the number of individuals who at present spend their working lives caring for the elderly and, of course, a lessening of the burden frequently imposed on younger relatives. Society as a whole would greatly benefit from such changes.

References 1 World Health Organisation (1991). World Heaith Statistics, p10. WHO, Geneva. 2 Olson, C.B. (1 987). A review of why and how we age: a defence of mutifactorial aging. Mech. Ageing Dev. 41,i-28. 3 Holliday, R. (1 995). Understanding Ageing. Cambridge University Press.

Robin Holliday is at the CSlRO Division of Biomolecular Engineering, PO Box 184, North Ryde, NSW 2113, Sydney, Australia.