Biological Aging Is A Disease And It Is Time To Recognize It As Such

Aging is often described as a risk factor for disease (Niccoli and Partridge, 2012). Indeed, the risk for hundreds of diseases, the so called age-related diseases, is increased with age and some of these diseases (such as Alzheimer’s disease) never occur in young people. I and others have argued that aging itself should be called a disease (Bulterijs et al., 2015; Gems, 2011, 2015; Lustgarten, 2016; Zhavoronkov and Bhullar, 2015). Interestingly, aging has been described as a ‘disease complex’ in the older literature (Perlman, 1953).   

But can something that increases the risk for disease (a risk factor) be a disease in itself? The answer is undoubtedly yes. Take for example diabetes which is a disease but also increases the risk for various other diseases such as diabetic nephropathy, retinopathy, neuropathy, atherosclerosis, and various cancers. Or the “accelerated aging” disease Hutchinson-Gilford Progeria Syndrome (HGPS) that increases the risk for heart disease. 

The US Food and Drug Administration (FDA) defines disease as “damage to an organ, part, structure, or system of the body such that it does not function properly (e.g., cardiovascular disease), or a state of health leading to such dysfunctioning (e.g., hypertension); except that diseases resulting from essential nutrient deficiencies (e.g., scurvy, pellagra) are not included in this definition” (21 CFR 101.93(g)(1)). Aging fits this definition well as most scientists believe that aging is caused by the accumulation of cellular and molecular damage leading to impairment of normal physiological functioning of cells, tissue, organs and bodily systems which in turn causes age-related diseases and increased risk for death (Aunan et al., 2016; Johnson et al., 1999; López-Otín et al., 2013). Furthermore aging is also a risk factor for other diseases (Niccoli and Partridge, 2012). Therefore aging fits the first and the second part of the definition of disease. Finally, aging is not caused by a nutrient deficiency and hence all conditions to label it as a disease are met.     

Aging has a 100% mortality rate which puts it in a limited group of diseases that kill all affected individuals. Even a feared disease like ebola only has an average mortality rate of 50% (WHO). The most deadly infectious disease is rabies but even this disease does not reach 100% mortality rate as 14 people so far have been reported to have survived the disease (Manoj et al., 2016). And many inheritable diseases have incomplete penetrance meaning that while some carry the disease gene (to be technically correct we should say allele) they do not become sick (Lobo, 2008). Aging in contrast has complete penetrance and is universally deadly.  

One argument used against labelling aging as a disease is that aging is universal among humans. Everyone ages. In contrast ‘classical diseases’ never affect everyone in a population. Though, we should point out that some diseases such as common colds are nearly universal (Caplan, 2005). Let us do a thought experiment (the scenario is biologically impossible; it’s very common for thought experiments to be impossible to actually conduct, rather they are used to think about the implications of what would happen if something was possible). What if humanity was suddenly hit by a pandemic that spread like wildfire through the human population eventually affecting every human on earth. At the early phase before the infection had spread to every person on earth we would call it a disease. Paradoxically, the moment the last human on earth becomes infected we would have to switch our thinking and stop calling the infection a disease as it is now an universal condition among humans. Clearly, this is ridiculous.               

A child with HGPS

It is also interesting to remark that ‘accelerated aging’ syndromes such as HGPS are classified as diseases while ‘normal aging’ is not. As discussed in the previous paragraph a common argument against classifying aging a disease is that it is universal. I believe that this stems from an error in the way in which we separate the normal from the abnormal in medicine. How do we know that a systolic blood pressure of 150 mmHg is abnormally high? Well, we measure the blood pressure of many people and find that the data have a normal distribution. Then we say that everyone who is more than a certain amount away from the average has an abnormal blood pressure (the normal range for systolic blood pressure is 80-120 mmHg). However, the normal reference depends on age and sex (Boorse, 1975). For example, we do not consider the lack of sperm production in male babies to be a disease because we do not use what is normal in adults as a reference for what is normal in babies (Boorse, 1977). Hence the age-stratification in physiological variables makes perfect sense for separating early life (development) from the adult state. The risk is that such thinking shouldn’t be extended further to create an artificial division between “young adults” and “elderly”. Development is a beneficial process while decline is not.   

People who are old but only suffer minor inconveniences and thus lack any clearly distinguishable pathology are often described as “healthy agers” or “successful agers” or “aging well”. This terminology is very popular, think for example about the “European Innovation Partnership on Active and Healthy Ageing”. Nobody dies from being healthy. It is clear that even elderly people who do not suffer from clear disabilities still have underlying disease processes going on otherwise they wouldn’t die. Furthermore, even the most healthy of the elderly suffer from a decrease in various bodily functions such as cognitive function, bone mass, renal function, immune function, hearing, and vision (Young, 1997; Zhavoronkov, 2013). In 2006 Leonid Gavrilov and Natalia Gavrilova already pointed out that “healthy aging” is an oxymoron (Gavrilov and Gavrilova, 2006). Imagine the bewildered and surprised looks one would get if one applied this terminology to other diseases: “healthy cancer” or “successful AIDS”. 

People are described as “healthy aging” or “successful aging” or “aging well” when their physiological functions decline but not to the extent that they cross the disease threshold. Image credit: Sven Bulterijs.

Some argue that calling aging a disease could lead to ageism, the discrimination of elderly people for being old. This argument however makes little sense as one would then have to argue to eliminate the concept of disease entirely. In fact, I would argue that not labeling aging a disease is a form of ageism as we ignore a whole segment of the population who is suffering from a deadly affliction that we do not even want to recognize as a disease in need for medical treatment.  

Finally, I would like to point out that many health problems in the elderly are also not yet recognized as diseases despite fitting the definitions of one. Over time more and more health problems that were once considered part of ‘normal aging’ have been reclassified as diseases (e.g. isolated systolic hypertension, Alzheimer’s disease, and osteoporosis) (Izaks and Westendorp, 2003; Gems, 2011). Currently the World Health Organization (WHO) is revising the International Classification of Disease (ICD). The new version (ICD-11) is expected to be implemented in 2018. While it is unrealistic to expect that we can convince the WHO at this moment to include aging as a disease in the ICD-11 (hopefully we will have the momentum needed to succeed at that by the time of the ICD-12) we can lobby to have multiple ‘aging syndromes’ recognized as diseases in the ICD-11. In fact just recently an ICD code was given to sarcopenia (muscle mass loss in old age) (Anker et al., 2016).

 

References
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