It's time to add aging to the list of diseases
It is time to classify biological aging as a disease
Sven Bulterijs et al., Frontiers in genetics, 2015
Translated by Evgenia Ryabtseva
History of disease definitionsOne of the most important determining factors in distinguishing between norm and pathology (disease) is the historical context (Moody, 2001/2).
Some conditions previously considered as diseases are now no longer considered as such. For example, the escapes of black slaves from plantations were considered manifestations of a disease known as drapetomania (uncontrolled desire to run away from home). To combat this disease, even medical "treatment" was used (Reznek, 1987). Similarly, masturbation was also regarded as a disease and was treated by methods such as removal or cauterization of the clitoris (Reznek, 1987). Finally, homosexuality was considered a disease as early as 1974 (Reznek, 1987).
In addition to the social and cultural influence on the formation of the definition of disease, new scientific and medical discoveries lead to a revision of what is a disease and what is not (Butler, 2008). For example, fever was once considered an independent disease, but the understanding that various causes can lead to its development has transferred it to the status of a symptom (Reznek, 1987). Conversely, a number of conditions currently recognized as diseases, including osteoporosis, isolated systolic hypertension and senile Alzheimer's disease, were in the past considered elements of normal aging (Izaks and Westendorp, 2003; Gems, 2011). WHO officially recognized osteoporosis as a disease only in 1994 (WHO, 1994).
Modern definition of the diseaseThe disease is a complex phenomenon and the modern definition should take into account both its biological and social explanation.
According to the medical explanation, the disease is any anomaly of the structure or function of the body that differs from that caused directly by physical damage. At the same time, the latter can lead to the development of the disease (Marcovitch, 2009). The disease has a specific cause and recognizable manifestations and symptoms. It can affect humans, other animals and plants (Martin, 2010).
The social aspect of the disease is significant in cases where it is necessary to distinguish between healthy and pathological conditions. This process is largely determined by the context of the assessment and, given the WHO definition of health as "a state of complete physical, mental and social well-being, and not just the absence of diseases or physical defects", illness cannot be considered simply as the opposite of health (WHO, 1946). "A person dying of hunger is not considered to suffer from a disease, but he also cannot be called healthy" (Reznek, 1987).
Reznek (1978) demonstrates that from a philosophical point of view, diseases are not a "natural phenomenon". If all diseases had a common specific essence that made them diseases, an unidentified disease could be classified simply by comparing it with already known pathologies and checking whether it corresponds to the same "natural phenomenon", such as tuberculosis or cancer. The purpose of distinguishing between a disease and its absence is to create a classification of conditions that can be cured with the help of medicine. In many cases, it may seem that the definition of a disease does not make any sense, since there are no necessary and sufficient conditions necessary to recognize them as diseases, and not as separate pathological conditions, such as injuries, disability and malformations.
Despite the complexity of unambiguous definition, we can simplify our definitions of the disease and our approach to their treatment by grouping certain pathologies. For example, cholera, tuberculosis and pneumonia are independent diseases, but can be considered together as bacterial infections. Similarly, HIV, influenza and measles are separate disorders of normal health, classified in one group as caused by viral pathogens. The division of diseases into similar classes greatly facilitates primary treatment strategies, which, among other things, is the main reason for the need to create a definition of the disease. Can we follow the same approach and create a fundamentally new group that will allow us to consider the aging process as an independent disease?
Is aging a disease?Traditionally, aging was considered as a natural process and, accordingly, was not considered a disease (Callahan and Topinkova, 1998; Hayflick, 2007).
This may be a kind of consequence of the allocation of the problems of aging to the independent research discipline – gerontology (Blumenthal, 2003). Some authors go so far as to draw a line between the internal processes of aging (the so-called "primary aging") and diseases of advanced age ("secondary aging") (Hazzard, 2001). For example, dermatologists consider solar heroderma – accelerated aging of the skin under the influence of solar ultraviolet radiation – a condition leading to the development of pathology (Rabe et al., 2006). At the same time, age-related skin aging is considered the norm.
Aging is considered separately from diseases, but is considered a risk factor for their development (Hayflick, 2002; Collier et al., 2011; Niccoli and Partridge, 2012). An interesting fact is that hereditary conditions characterized by accelerated aging, such as Hutchinson-Guilford syndrome (childhood progeria), Werner syndrome (adult progeria) or congenital dyskeratosis are considered diseases. Progeria is recognized as a disease, but when the symptoms characteristic of it develop in 80-year-olds, they are considered normal and do not require medical intervention (Kaplan, 2005).
Usually, opponents of classifying aging as a disease use as an argument the fact that aging is a natural universal process, whereas diseases are considered as deviations from the normal state (Kaplan, 1992). The distinction between norm and pathology may depend on the intentions, purpose and function of such a separation (Hausman and Kennedy, 1975; Becker and Becker, 2001). The evolutionary theory of aging states that the cause of aging is a decrease in selection pressure in relation to alleles that have a detrimental effect on the body at the later stages of its life (Williams, 1957). Thus, aging is a consequence of an evolutionary omission, and not the goal of evolution (Olshansky et al., 2002). If aging does not serve any specific purpose, then the idea of it as a natural process may be erroneous (Kaplan, 2005).
In the medical context, the norm is usually considered as a condition that does not go beyond the normalized range of values for a particular age and gender, whereas diseases are considered as deviations from these normal values (Assaf et al., 2010; Boorse, 1975). Thus, a person with a blood pressure of about 120/80 is considered normal, while blood pressure above 140/90 and below 85/55 is considered abnormal and is a sign of the disease (WHO, 2015).
Stratification of normalized ranges of values depending on age is necessary to separate fully formed adults from children who continue their development. This avoids, for example, the recognition of the absence of developing sperm cells in male infants as a disease (Boorse, 1977).
The division of older and younger adults into separate groups, on the contrary, does not have a single convincing biological argument. Instead, it puts aging in a separate category, despite the evidence that aging is a deviation from a more desirable state with the physical and mental capabilities of youth (Callahan and Topinkova, 1998). While such a statement can be considered "ageist", this concept is based on a misunderstanding of what is meant by the word "youth". Aging as the passage of time and the accumulation of wisdom is not undesirable, but the accompanying physiological extinction of the body is undoubtedly such (Mackey, 2003).
Representatives of the vast majority of species go through the aging process. While aging is an almost universal phenomenon, it should be noted that other medical problems, such as atrophy of muscle tissue leading to sarcopenia, a decrease in bone mass and density leading to osteoporosis, compaction of arterial walls leading to hypertension and atherosclerosis, as well as atrophy of brain tissue leading to dementia, are almost universal in the human population, they refer to diseases requiring medical interventions (Bierman, 1985; Izaks and Westendorp, 2003; Gems, 2011; WHO, 1994). Also, the results of the examination of samples obtained during autopsy indicate that amyloidosis can develop in almost all elderly people (Blumenthal, 2002) and in one of the studies it was indicated as the cause of death of approximately 70% of people over the age of 110 (Coles and Young, 2012). Maybe we should remove amyloidosis from medical textbooks as an age-related disease just because it develops in almost every elderly person? It should be noted that this proposal is seriously considered, for example, by Blumenthal (1995).
David Gems notes that the universality of aging does not exclude its belonging to diseases, but rather indicates that aging is a "special form of disease" (Gems, 2011). Even considering that aging is a natural process, it should not fall out of the scope of medicine. Other natural processes, such as pregnancy, cosmetic problems and other conditions that are also not considered diseases, are considered as targets for medical interventions, such as contraception, in vitro fertilization and plastic surgery (Boorse, 1975).
While most people still do not consider aging as a disease, some have already had doubts about this. There are proposals to consider aging as a disease (Kaplan, 1992; Gems, 2003, 2011), a syndrome (Esser and Keller, 1976) or a "complex of diseases" (Perlman, 1953, 2003). While many experts in the field of aging openly declare that the universality of the aging process indicates that it is not a disease, aging corresponds to the existing medical definition of the disease. There is no doubt that aging is a "disastrous violation of the structure and functions of the body." It is becoming increasingly obvious that aging has special causes, each of which can be suppressed at the cellular or molecular level, as well as recognizable manifestations and symptoms (Lopez-Otin et al., 2013).
The relativity of the components of the concepts "disease" and "norm" was recently demonstrated in the statement of the American Medical Association, according to which obesity is a disease (American Medical Association, 2013). Obesity, as well as aging, does not correspond to the traditional characteristics of the disease. However, classifying such a condition as obesity as a disease greatly facilitates the development of medical interventions. Since aging is ideally suited to the definition of a disease, there is a shaky consensus that it should be considered as an independent pathological process, and not benign age-related changes that increase the risk of developing diseases.
Advantages of classifying aging as a diseaseCallahan and Topinkova (1998) write: "In short, in addition to the fact that aging perfectly corresponds to the description of the disease, the advantage of considering it in this way is to reject the imaginary inevitability of the label "natural".
This approach facilitates the recognition of appropriate medical interventions aimed at eliminating undesirable conditions associated with aging, or at their elimination." The aim of biomedical research is to enable people to maintain "as good health as possible for as long as possible" (de Magalhaes, 2014). The attribution of aging to diseases encourages grantees to increase funding for research in the field of aging and the development of biomedical procedures aimed at slowing down this process (Kelland, 2010). Engelhardt argues that recognizing something as a disease implies the need for medical intervention (Engelhardt, 1975). Moreover, classifying a condition as a disease is an important point for the mechanism of reimbursement of treatment costs by insurance companies (Reznek, 1987).
Over the past 25 years, by influencing the fundamental processes of aging, biomedical researchers have managed to improve the health and life expectancy of model organisms, ranging from roundworms and fruit flies to rodents and fish. Today, we have effective approaches at our disposal that make it possible to increase the maximum life expectancy of C.elegans worms by more than 10 times compared to the natural one (Ayyadevara et al., 2008) and drosophila flies and mice by more than 2 times (Bartke et al., 2001; Sun et al., 2002), as well as by 30% and 50%, respectively, of carp–toothed fish and rats (Zha et al., 2008; Valenzano et al., 2006) (see graph).
The current possibilities of influencing the fundamental processes of human aging are very limited. However, taking into account the observed progress in the development of geroprotective drugs, regenerative and personalized medicine methods, in the near future we will be able to slow down the aging process (Bulterijs, 2011; 2012). Finally, it should be noted that classifying aging as a disease will automatically change the standards applied by the FDA to the corresponding therapeutic approaches to more stringent ones (Gems, 2011).
ConclusionWe believe that aging should be considered as a disease, despite the fact that this disease is a universal and multi-system process.
The modern US healthcare system does not recognize the aging process as a fundamental cause of the development of chronic diseases affecting the elderly. This has the opposite effect, and as a result, about 32% of all public health insurance costs in the United States are spent on treating patients with chronic diseases during the last two years of their life, without significantly improving their quality of life (Cooper, 1996; Neuberg, 2009). The US healthcare system is untenable both from a financial point of view and from the point of view of health and well-being. Even minimal relief of the aging process by stimulating research in this area, as well as the development of geroprotective drugs and regenerative medicine methods, can significantly improve the health and well-being of older people and save an inoperable health care system.
For a list of the literature mentioned in the text, see the pdf file attached to the original article.
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