Aging is a disease - updates on the controversy

These days a striking survey result was making the rounds on twitter. The main paper titled “Disagreement on foundational principles of biological aging” buries the lede as there is an even more exciting finding showing what topic researchers disagree on less than they used to. You guessed it.

So 39 votes in favor and 35 against means that, at least within this convenience sample from the 2022 Systems Aging Gordon Research Conference, there is now a strong majority of aging researchers who believe that aging is a disease.

Back in the day, people would think you were a crackpot if you wanted to substantially slow or reverse aging. They would feather and tar you and force you to eat Dunkin Donuts to break your Calorie Restriction if you did. Back in the day the words “aging is a disease” were unspeakable.

Are we slowly changing minds and winning because truth always prevails?

Why aging is a disease

Aging is a disease because it is a harmful biological process that kills people.

Aging is a process that kills and disfigures people, a process that tears apart families, extinguishes memories, and consumes bodies from the inside. One foam cell and one metastasis at a time.

As far as I'm concerned, this is as clean and obvious a case as it gets. My personal belief is that the “aging is not a disease” side suffers from motivated reasoning, but we will give them the benefit of the doubt. Not least because vice versa, the “aging is a disease” side—largely championed by more radical life extensionists, immortalists, and transhumanists—could equally suffer from motivated reasoning.

We shall call these reasons on both sides “political” or “strategic” and discuss them after the science-based arguments.

1 Aging is not a disease because it is universal

One argument that I have heard often enough is that aging cannot be a disease because it is universal. To support this argument anti-disease proponents will pick a definition of disease that specifically uses the word “abnormal” and then argue that aging is normal.

A disease is "An abnormal condition that affects the structure or function of part or all of the body" (NCI Dictionary of Cancer Terms)

On the other hand, there are a lot of definitions of disease that are much more permissive. See the Oxford definition given by google ”a disorder of structure or function in a human… especially one that has a known cause and a distinctive group of symptoms, signs, or anatomical changes”

Even using the first definition we are justified in calling aging a disease. There is absolutely no reason why normal should not refer to an adult under optimal health. Aging is clearly an abnormal deterioration of your 20-year old self.

Of course, you could play word games telling me that children are sick and abnormal by this definition hence I cannot use it. Or maybe we don’t do that.

Definitions can be justifiably axiomatic. It would be nothing strange if we called aging a disease given our scientific understanding of aging and the commonly used definitions of disease. If we have to define aging as an abnormal deviation from optimal adult health. Oh, my god, then so be it.

Perhaps more intuitively we can look at some diseases that are currently recognized as such. Upper respiratory tract infections are diseases, right? But then there is no one who never gets sick, because these diseases are circulating in all human populations. Does this mean that colds are not a disease because they affect 99.999% of the population?

If we had never found a way to slow the spread of HIV, within a few generations, all of humanity would be infected and lifespans would drop by decades. Would HIV stop being a disease? Yes, perhaps it would, a hardliner might argue. And they are not totally wrong. Human bodies have domesticated many viruses over the millennia, some of which do not appear to be pathogenic. But pathogenic means to cause harm. HIV would stop being pathogenic when it stops shortening lives.

If it will kill my father and mother it clearly causes harm. Isn’t it callous to claim that this biological suffering inflicted by aging is not pathogenic?

2 Aging is not a disease because it is a risk factor

If aging is not a disease because it is a risk factor, then this also applies to other similar conditions. If you want to define syndromes as non-diseases then you can go ahead. Tell the doctors while you are at it and redefine all our medical knowledge just so you do not need to call aging a disease.

Down Syndrome, Turner Syndrome, Klinefelter Syndrome, Marfan Syndrome, Tourette Syndrome, Rett Syndrome, Ehlers-Danlos Syndromes, Edwards Syndrome, Patau Syndrome, Angelman Syndrome.

A syndrome is a disease that is defined by a collection of symptoms or abnormalities, not all of which need to be present, rather than being one very specific condition. Often these diseases are called disorders to account for this distinction. I would be happy to call aging a disorder or syndrome if that is what it takes. All these disorders have their well-earned place in the International Classification of Diseases (ICD).

Williams Syndrome, DiGeorge Syndrome, Prader-Willi Syndrome, Asperger Syndrome, Sturge-Weber Syndrome, Waardenburg Syndrome, Noonan Syndrome, Cri-du-chat Syndrome, Fragile X Syndrome, Apert Syndrome, Beckwith-Wiedemann Syndrome, Brugada Syndrome.

Hey, none of you are sick now. Feel free to go home! Having too many chromosomes is just a risk factor for early death and mental disability, apparently.

Guillain-Barré Syndrome, Carpal Tunnel Syndrome, Horner Syndrome, Sjögren Syndrome, Zollinger-Ellison Syndrome, Wolff-Parkinson-White Syndrome, Superior Vena Cava Syndrome, Hemolytic Uremic Syndrome.

https://www.who.int/standards/classifications/frequently-asked-questions/old-age

We lost this round with the WHO (see also ref. 2), but we will be back. Aging kills more people than any of the trisomies and produces at least as much suffering if not more. Aging needs to stand on equal footing with the other disorders and syndromes. Being a collection of diseases has never stopped the ICD.

3 Aging is not a disease because it is a continuous process

Let’s say, this argument will make a lot of people working in primordial prevention very unhappy. As it turns out, almost every pathology and disease results from a continuous underlying process that can be intercepted, slowed or modulated. Indeed, time travel into the future has not been invented so things do generally follow a logical causal chain. I suppose falling from the 19th floor could be regarded as an abrupt disease process, but most other diseases aren’t.

For example, ischemic heart disease results from ruptured or stenosing plaques, which result from atherosclerosis which results from advanced calcifying plaque, which results from early uncalcified plaques which results from advanced fatty streaks which start with the infiltration of a single macrophage that turns into a foam cell.

Cancer starts with DNA damage, some of which goes unrepaired resulting in mutations, some of which hit the right genes turning off tumour suppressor genes or activating growth pathways. Some of these cells obtain a growth advantage and start outcompeting neighboring cells and acquire more driver mutations. Importantly, the underlying process of clonal expansion and pre-cancerous lesions, in one form or another, is universal. Would this mean that cancer cannot be considered a disease because ultimately everyone gets it?

4 Political and strategic arguments

Both proponents and opponents implicitly agree that “disease” is a political term and not a medical one. Even if they do not admit it, most opponents of the disease notion will at some point argue that defining aging as a disease would make someone feel bad, it would hurt and upset older people. This is an appeal to emotion and not to science. Which is fine by me, but in such a case we should be intellectually honest and admit that we are re-classifying a real disease to be a non-disease for political reasons.

Homosexuality used to be a disease. Whether gambling or different forms of food addiction (obesity?) are a disease has been contentious for a long time. The concept of disease is heavily influenced by moral and political world views.

Whatever our opinions on the matter, we should still emphasize that sick people are not inferior people. I suffer from health conditions which are rightly called diseases. That is a normal part of life. We are all sick, we are all slowly dying, and it doesn't make us less human. If anything more. Which is not an argument to embrace biological suffering but to reflect on the core values of humanity and which ones we can, and should, do without.

Proponents of the aging is a disease idea will usually claim that classifying aging as a disease will accelerate progress towards slowing of aging. It certainly would, as far as I can tell. But this is a political and not a scientific argument. On the margin, there is no process which wouldn’t be slightly accelerated by this classification. Whether it concerns IRBs, insurance or the FDA. Classifying aging as a disease would take away ammunition from IRBs known to ask vicious, and often inane, questions. Insurance often refuses to cover treatments for conditions that are not regarded as a disease e.g. obesity, mental health or addictions. With stronger likelihood of insurance coverage, the development of longevity medicines would be significantly derisked. It is impossible to believe, in good faith, that the FDA and pharma is ruled by all-knowing technocrats. If, on the margin, there are 5% of employees who incorrectly believe that aging is “natural” and half of those would be swayed over the years if the WHO and medical establishment came out saying that aging is a disease, that would still be an incremental improvement at every stage of the pipeline.

Personally, I believe classifying aging as a disease would be at the very least a moderate boost to productivity and derisking. Although I agree we should not oversell the benefits. If there was an immediately profitable path forward to slow aging, and thereby age-related disease, pharma and FDA would have taken this path by now. No, curing aging will be a hard task and we simply should not make it harder than it needs to be.

Going forward

It is often said that scientists are not entitled to have strong opinions. But this is at odds with good science communication and to some extent even the scientific process. One of my driving forces has been the rightful anger at people who are clearly seeing a sinking ship with very few lifeboats, alarm balls ringing loudly, and yet go on about their daily life, sipping cocktails at the bar, having philosophical conversations that do not even concede the minor point that we perhaps should acknowledge that the ship is sinking, and that overall, this is bad, very, very bad — regardless of whether we actually want to do something about the slow process that transforms the ship into a coral reef and all its current inhabitants into fish food and nutrients for the ocean.

One other key argument on the anti-disease side is that defining aging as a disease would lead to inconsistencies. However, as pointed out before, classifying aging as normal also leads to inconsistencies. How can this be, that both definitions are flawed?

Just like the definition of life or of intelligence and reasoning, the definition of disease will never be perfect. Is a virus alive? What about a virus that has more genes than an obligate endoparasitic bacterial species? Is a large language model that perfectly and flawlessly mimics a human alive? You get the idea.

Let me badly butcher and misinterpret Kurt Gödel here for a second. Basically, any sufficiently complicated and powerful system cannot be entirely free of contradictions. The same is true for ethics and powerful defining frameworks. The implication is that this will always leave the door open for politics and strategizing.

Nevertheless, our definitions and frameworks should strive to be reasonable, free of contradiction, unnecessary assumptions and to be useful in the real world. Defining aging as a disease satisfies all these conditions.

A cynical joke often repurposed by the enemies of longevity research goes like this “Science advances one funeral at a time”. I refuse to believe this quip and I hope that I can change your opinion so we can all work together on this problem.

References

1. Gladyshev, Vadim N., et al. "Disagreement on foundational principles of biological aging." PNAS nexus 3.12 (2024): pgae499.

2. Rabheru, Kiran, Julie E. Byles, and Alexandre Kalache. "How “old age” was withdrawn as a diagnosis from ICD-11." The Lancet Healthy Longevity 3.7 (2022): e457-e459.