This article has Open Peer Review reports available.
Ill or just old? Towards a conceptual framework of the relation between ageing and disease
© Izaks and Westendorp; licensee BioMed Central Ltd. 2003
Received: 24 July 2003
Accepted: 19 December 2003
Published: 19 December 2003
Is this person ill or just old? This question reflects the pondering mind of a doctor while interpreting the complaints of an elderly person who seeks his help. Many doctors think that ageing is a non-disease. Accordingly, various attempts have been undertaken to separate pathological ageing from normal ageing. However, the existence of a normal ageing process distinct from the pathological processes causing disease later in life can be questioned.
Ageing is the accumulation of damage to somatic cells, leading to cellular dysfunction, and culminates in organ dysfunction and an increased vulnerability to death. Analogously, chronic diseases initiate early in life and their development is slow before they become clinically apparent and culminate in disability or death. The definition of disease is also subject to current opinions and scientific understanding and usually, it is an act of individual creativity when physical changes are recognised as symptoms of a new disease. New diseases, however, are only rarely really new. Most new diseases have gone undiagnosed because their signs and symptoms escaped recognition or were interpreted otherwise. Many physical changes in the elderly that are not yet recognised as a disease are thus ascribed to normal ageing. Therefore, the distinction between normal ageing and disease late in life seems in large part arbitrary.
We think that normal ageing cannot be separated from pathological processes causing disease later in life, and we propose that the distinction is avoided.
Is this person ill or just old? This question reflects the pondering mind of a doctor while interpreting the complaints of an elderly person who seeks his help. Should the complaints be explained by the normal ageing process or is there a disease as yet undiagnosed? Many attempts have been undertaken to separate pathological ageing from normal ageing. The distinction, however, has remained unclear as it appears to be dependent on current opinions and the extent of our scientific understanding . Isolated systolic hypertension, for example, has long been considered normal in elderly people. Today, it is recognised as an outcome of atherosclerosis and a principal cause of cardiovascular disorders that necessitates proper treatment, also in the very old . Furthermore, it is confusing that the description of normal ageing as a series of cumulative, universal, intrinsic and deleterious changes , also applies to many chronic diseases .
The aim of the present paper is to explore the relation between ageing and disease late in life. To that end, we provide the biological definition of ageing, comment on the definition of disease, and present a conceptual framework of the ageing process that can be applied in clinical medicine. This framework can help doctors in understanding the physical changes that they observe in elderly patients without having to decide whether their patient is ill or just old.
The biological definition of ageing
Ageing is defined as those processes in an organism that increase the mortality risk as a function of time . This definition seems rather simplistic and it looks as if all key parameters of ageing are ignored by it. However, the reverse is true. Imagine that the mortality risk does not increase with age. In that case, living cautiously and avoiding accidents would imply eternal life. However, death is a fact of life and over the years the mortality risk inevitably increases despite all our efforts to prevent it.
The definition of disease
Defining disease is difficult. New diseases continually arise . Usually, it is an act of individual creativity when certain physical changes are recognised as symptoms of a new disease. A disease is more easily accepted as such when it has therapeutic consequences. New diseases, however, are only rarely really new. Most new diseases have gone undiagnosed because their signs and symptoms escaped recognition or were interpreted otherwise. Many physical changes in the elderly that are not yet recognised as a disease are thus ascribed to normal ageing. In the past, this has not only happened to isolated systolic hypertension but also, for example, to osteoporosis. Therefore, the distinction between normal ageing and disease late in life seems in large part arbitrary .
An effect, or a disease, can be explained by different combinations of component causes (figure 2). Each combination constitutes another sufficient cause. Sufficient causes that have the same effect may share some of their component causes.
On the other hand, some component causes may be part of different sufficient causes, each having its own distinct effect. In medicine, this phenomenon is recognised as different diseases sharing the same risk factors. For example, smoking is not only a component cause of atherosclerosis, it is also a component cause of lung cancer. The specific combination with other component causes determines which effect becomes clinically apparent.
Death can be explained by a line of reasoning similar to the one that has been put forward here to explain the physical changes with ageing (figure 3). Death has several sufficient causes. Since their origin is complex, most sufficient causes of death are likely to consist of a large number of component causes. At puberty, when the mortality risk is lowest, there are only a few component causes. As we grow older, the sufficient causes that constitute the various causes of death are step by step completed. Every new component cause increases the chance of completing one of the sufficient causes. The model thus explains the increased mortality risk in old age, the hallmark of ageing .
Example: unsteadiness, gait disorders, and death
Unsteadiness is a common complaint in elderly people, and, in most cases, it cannot be ascribed to one factor. Therefore, let us suppose that someone has accumulated the following component causes (illustrated in figure 3): A, a stooped posture; B, polyneuropathy; C, high-heeled shoes; D, an impaired vision; and E, a clavus under the sole of the foot. Let us also suppose that these five factors are sufficient to cause a feeling of unsteadiness. Then, it becomes clear why the purchase of other footwear, the acquirement of new glasses or the removal of the clavus is sufficient for the complaints to disappear. The cause becomes insufficient.
Subsequently, the patient may have accumulated the following new component causes: F, isolated systolic hypertension; G, periventricular white matter lesions; and H, global atrophy of the brain. In combination with factors A and B, the factors F, G and H complete a sufficient cause of an abnormal gait. Some doctors may diagnose a disease, for example, small vessel disease due to hypertension. Others may interpret the gait disturbance as an often occurring, normal phenomenon in elderly people, and thus call it a senile gait disorder. However, irrespective of the interpretation of their cause, all gait disorders in elderly people are associated with an increased mortality risk and should therefore be interpreted as abnormal .
One day, our patient takes a fall (I) and develops a subdural haematoma (J). The accumulation of these two component causes completes a sufficient cause of death, and the patient expires. The above example is an illustration of the accumulation of component causes being an explanation for the occurrence of physical changes, diseases and the increase in mortality risk in elderly people. In addition, the conceptual framework makes clear why some elderly people can be considered to be frail.
Frail people may function independently when feeling well, but are at high risk of becoming dependent [11, 12]. Since many physiological functions decline with increasing age, they have a reduced reserve capacity. One single factor is then sufficient to cause a cascade of events leading to the deterioration of many body functions, and eventually death. In the conceptual model, this corresponds to the situation in which several nearly completed sufficient causes share a missing component cause. A single component cause may complete a series of sufficient causes and will set off several effects. As a consequence, a number of diseases become clinically apparent at the same time if only one new factor (component cause) is added.
The presented conceptual framework is an explicit formulation of two common ideas about ageing. First, there is consensus of ageing being associated with the accumulation of damage . Second, it has been recognised that chronic diseases initiate early in life and that their development is slow before they become clinically apparent and culminate in disability or death . Both ideas, however, are consistent with the accumulation of component causes, physical changes, and diseases later in life as has been described in the conceptual framework. As such this framework has major implications for the interpretation of physical changes in elderly people.
Many doctors think that ageing is a non-disease . Major textbooks on geriatric medicine and gerontology explain the occurrence of physical changes in elderly people as due to normal ageing or disease [15, 16]. The presented conceptual framework makes it clear that a similar process is causing ageing and disease in the latter part of life. Therefore, in our opinion, normal ageing cannot be separated from pathological processes causing disease later in life. As a consequence, we think that making a distinction between normal ageing and pathological ageing should be avoided.
According to the same reasoning, it is not appropriate to use old-age-specific normal values. The decision whether a body function of an elderly patient is impaired or not must be based on the same normal values that are used in young adults. In fact, this idea is not new.
Osteoporosis is defined relative to the average bone mineral density in young adults . This logic is not yet applied in all fields of medicine. For example, some authors propose lower normal values for haemoglobin levels in elderly people . In elderly people, however, all haemoglobin levels below the normal values in young adults are associated with excess mortality and must thus be considered as abnormal . In the same line of reasoning, we argue that the definition of normal values for cognitive and pulmonary function in the elderly has led to problematic concepts as late-life forgetfulness and senile lung [20, 21]. These concepts are used to explain an impaired cognitive or pulmonary function in the elderly without referring to disease. In our opinion, this is illogical. There is no good reason why the normal values for functions in young adults are not applied in adults at all ages.
Finally, the presented conceptual framework is in line with the observation that frailty is more a constellation of many conditions than a discrete clinical entity . Accordingly, frailty is depending on the abundant presence of other risk factors, not on specific risk factors. Therefore, we think that it is erroneous to investigate the specific risk factors of frailty. With the purpose of preventing frailty in elderly people, we should investigate the risk factors (component causes) of diseases in the latter part of life.
The existence of a normal ageing process distinct from the pathological processes causing disease later in life can be questioned.
Ageing is the accumulation of damage to somatic cells, leading to cellular dysfunction, and culminates in organ dysfunction and an increased vulnerability to death.
Analogously, chronic diseases initiate early in life and their development is slow before they become clinically apparent and culminate in disability or death
In addition, the definition of disease is subject to current opinions and scientific understanding.
Based on the above, normal ageing cannot be separated from pathological processes causing disease later in life, and we therefore propose that the distinction is avoided.
Avoiding the distinction between normal and pathological ageing has important implications for the clinician. For example, the use of old-age-specific normal values appears to be inappropriate.
- Rise and fall of diseases:. Lancet. 1993, 341: 151-152. 10.1016/0140-6736(93)90009-6.Google Scholar
- Staessen JA, Gasowski J, Wang JG, Thijs L, Boissei JP, Coope J, Ekbom T, Gueyffier F, Liu L, Kerlikowske K, Pocock S, Fagard RH: Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000, 355: 865-872. 10.1016/S0140-6736(99)07330-4.View ArticlePubMedGoogle Scholar
- Strehler BL: Definitions, criteria, categories, and origins of age changes. In Time, cells, and aging. 1962, New York: Academic Press, 4-32.Google Scholar
- Solomon DH: The role of aging processes in aging-dependent diseases. In Handbook of theories of aging. Edited by: Bengtson VL, Schaie KW. 1999, New York: Springer Publishing Company, 133-149.Google Scholar
- Finch CE: Introduction. In Longevity, senescence, and the genome. 1990, Chicago: The University of Chicago Press, 3-42.Google Scholar
- Kirkwood TB, Austad SN: Why do we age?. Nature. 2000, 408: 233-238. 10.1038/35041682.View ArticlePubMedGoogle Scholar
- Kirkwood TB: Evolution of aging. Nature. 1977, 270: 301-304.View ArticlePubMedGoogle Scholar
- Holliday R: Ageing in the 21st century. Lancet. 1999, 354 (Suppl): SIV4-View ArticlePubMedGoogle Scholar
- Rothman KJ: Causes. Am J Epidemiol. 1976, 104: 587-592.PubMedGoogle Scholar
- Bloem BR, Gussekloo J, Lagaay AM, Remarque EJ, Haan J, Westendorp RG: Idiopathic senile gait disorders are signs of subclinical disease. J Am Geriatr Soc. 2000, 48: 1098-1101.View ArticlePubMedGoogle Scholar
- Brocklehurst JC: The geriatric service and the day hospital. In Textbook of geriatric medicine and gerontology. Edited by: Brocklehurst JC. 1985, Edinburgh: Churchill Livingstone, 982-995.Google Scholar
- Rockwood K, Fox RA, Stolee P, Robertson D, Beattie BL: Frailty in elderly people: an evolving concept. CMAJ. 1994, 150: 489-495.PubMedPubMed CentralGoogle Scholar
- Fries JF: Aging, natural death, and the compression of morbidity. N Engl J Med. 1980, 303: 130-135.View ArticlePubMedGoogle Scholar
- Smith R: In search of "non-disease". BMJ. 2002, 324: 883-885. 10.1136/bmj.324.7342.883.View ArticlePubMedPubMed CentralGoogle Scholar
- Miller RA: The biology of aging and longevity. In Principles of geriatric medicine and gerontology. Edited by: Hazzard WR, Blass JP, Ettinger WH, Halter JB, Ouslander JG. 1999, New York: McGraw-Hill, 3-19.Google Scholar
- Masoro EJ: Physiology of aging. In Textbook of geriatric medicine and gerontology. Edited by: Tallis RC, Fillit H, Brocklehurst JC. 1998, Edinburgh: Churchill Livingstone, 85-95.Google Scholar
- Kanis JA: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994, 4 (6): 368-381.View ArticlePubMedGoogle Scholar
- Tietz NW, Shuey DF, Wekstein DR: Laboratory values in fit aging individuals: sexagenarians through centenarians. Clin Chem. 1992, 38: 1167-1185.PubMedGoogle Scholar
- Izaks GJ, Westendorp RG, Knook DL: The definition of anemia in older persons. JAMA. 1999, 281: 1714-1717. 10.1001/jama.281.18.1714.View ArticlePubMedGoogle Scholar
- Blackford RC, La Rue A: Criteria for diagnosing age associated memory impairment: proposed improvements from the field. Dev Neuropsychol. 1989, 5: 295-306.View ArticleGoogle Scholar
- Verbeken EK: The senile lung. Comparison with normal and emphysematous lungs: 2. functional aspects. Chest. 1992, 101: 800-809.View ArticlePubMedGoogle Scholar
- Hamerman D: Toward an understanding of frailty. Ann Intern Med. 1999, 130: 945-950.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2318/3/7/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.