Declaring the Importance of Classifying Aging as a Disease

To follow on from a recently linked article on the present regulatory state of affairs for aging research, below find another recent call for regulators and administrators to classify aging as a disease. Numerous researchers have issued opinions and position papers on the topic in the past few years, and to understand why this is the case requires an understanding of how regulation impacts the research funding landscape. From a regulatory standpoint aging is not currently considered a medical condition per se. In some classifications, deviation from normality is one of the baseline criteria, and hence universal phenomena like aging are not included, no matter how ugly the end result. In the case of regulation tied to the legal matter of whether or not it is permitted to offer a particular treatment, and in the US the FDA adopts an "all that isn't listed is forbidden" position, the omission of aging as a treatable condition is a big deal. It means that there is no straightforward path to commercialization of potential therapies for aging within the current framework, and this greatly raises the difficulty of obtaining funding for that goal.

Attempts to change this state of affairs are slow, expensive, drawn out affairs of official and unofficial lobbying. You can see one of the approaches presently underway in the forthcoming clinical trial of metformin, a drug highly unlikely to produce meaningful results in my opinion, but which is the thin end of the wedge when it comes to the scientific community trying to force change on the FDA in the matter of aging. The recent increase in calls to classify aging as a disease should be considered in this context: the word "disease" is just shorthand for "something that I'm allowed to try to treat, and can thus raise funding for." Now that slowing aging and the medical control of aging are accepted as a plausible, possible near future goal by much larger fractions of the research community, the regulatory straitjacket is becoming ever more uncomfortable.

In the case of the World Health Organization's International Statistical Classification of Diseases and Related Health Problems the situation is still all about money, but in this case the benefits sought are a little more indirect. Adding aging to the WHO classification scheme is a way to induce various bureaucracies around the world to direct thought, funding, and verbiage to aging in the context of possible treatments. This falls somewhere between an attempt to amplify advocacy for the treatment of aging and an attempt to expand government research funding, such as the National Institute on Aging budget, via existing mechanisms requiring adherence to the WHO classifications.

For my part, I think that striving to change the regulatory system from within is just another way of implicitly endorsing its existence. None of the vast costs imposed on medical research and development by FDA bureaucrats will go away if aging officially becomes a disease. The better way forward would be for researchers in the US to develop relationships with developers elsewhere in the world, such as the more advanced Asia-Pacific nations in which medical regulation isn't so overbearing and costly: commercialize elsewhere, and deliver services and therapies to the market via medical tourism. The result will be more new treatments, delivered more rapidly, and at lower cost. If the FDA continues to pile on the costs and time for regulatory acceptance of new therapies, more than doubled in the past ten years, alternative commercial ecosystems will develop. Not before time, to my eyes, and it is a pity that this process is not further along now. The best path ahead is to make the FDA and its ilk irrelevant, to bypass the broken system and grasp greater freedom, not to support the present bureaucratic suppression of medical research by spending years to slightly change its parameters.

Why Classifying Aging As A Disease Is Of Crucial Importance To Humanity

Most people have probably heard many times the idea that one can "grow old gracefully" and in a healthy way. This message is perpetuated by the fitness and health industry and pension companies love to show the image of happy, relatively healthy 65-year-olds who can finally escape dreaded work and do what they enjoy in life, for at least a few years before a period of serious disability and death. It is true that some people live over a century and delay many specific pathologies. I also agree that it is a more desirable scenario to die frail at 100 than earlier, but the fact is that what we define as biological aging is in itself a pathological problem, a problem that still suffers from a lack of research. While not every age-related change is studied, the damages can be broadly classified into categories, and specific biomolecular problems can be directly targeted.

While there is a small decrease in function between 20 and 40, the human body still remains "very healthy" until mid 40s when disease correlated to the aging process overtakes accidents/suicides as most common cause of death. Keeping the human body biologically under 50 years old would take away the vast majority of all disease, and even if biologically young people were obese and smoked, there would likely only be a small number of cases where these "unhealthy" habits caused lethal health problems. The problem with WHO and governmental programs is that these systemic pathologies destroying the body and generating ill health in the elderly are not yet considered to be a disease. I have worked trying to change this paradigm. Earlier this year I coauthored "It is time to classify biological aging as a disease", and Alex Zhavoronkov and his company In Silico Medicine have recently published a paper on this issue, to persuade the World Health Organisation to classify aging as a disease as a part of the International Statistical Classification of Diseases and Related Health Problems (ICD-11).

When I was a child I was told wrinkles signified wisdom and life experience, but didn't impact one's health in any way. Nowadays my brain is wired to spot the pathologies behind them; skins laxity and jowls linked to blood sugar crosslinking and destruction of collagen, dysfunction of matrix metalloproteinases and subsequent extracellular matrix degradation. Wrinkled skin is not simply a cosmetic issue, as senile skin is failing to perform its duties properly, similar to burned and scarred skin. Many old people become easily dehydrated, are less able to cope with temperature fluctuations, and they injure and bruise themselves easily due to the loss of components making up the main skin layer, the dermis. Skin aging in itself is yet not classified as a disease, but lesions have pathological names, and photo-aging caused by sun exposure, which shares molecular pathologies with intrinsic skin aging, is considered a pathological condition. What is humanity gaining by this hypocrisy?

Comments

I do think that this effort is important and I'm not antiFDA nor antiWHO. I think SRF should be more vocal on this and help these efforts to classify aging as a disease (through his advisory board and their contacts). Calico could also help, it's good for them.

Posted by: Antonio at November 19th, 2015 2:48 AM

Yes I've been thinking the same thing about Calico, Antonio. Google has such enormous clout here that I wonder if they could possibly do some persuading. They have to know about the regulatory issues, and why spend a billion dollars dedicated to treating aging only to be told that they won't be allowed to release any drugs because aging isn't recognized as an issue.

Posted by: Ham at November 19th, 2015 3:39 AM

Reason and others, do you have a view about which country or countries specifically would be most suitable for doing rejuvenation research and later establishing medical tourism related to rejuvenation?

Posted by: sk at November 19th, 2015 4:56 AM

@sk: Clinics in Vietnam and Thailand were used by some of the first stem cell therapy companies. India has a good research and medical community. China has some notable medical tourism destinations.

Posted by: Reason at November 19th, 2015 6:48 AM

Reason,

Why wouldn't a company like calico or HLI, which both clearly want to develop interventions for aging simply open up shop in one of the areas you mentioned. They certainly have the funds to do so. Is it because they're an American based company, and they can't? Or do you think they're going to try their hand at changing the FDA's stance on aging? It seems like it would be a lot of money wasted developing treatments to be told no by the FDA... So maybe there's something going on there quietly?

Posted by: Ham at November 19th, 2015 9:31 AM

I'm a little puzzled why some of you think it's so important for aging to be officially classified as a disease. Since "aging" is just a convenient name for the diseases of aging, what's the point in engaging in what is essentially semantics? While it's true that not all of the degenerative conditions of aging such as sarcopenia have an official disease designation yet, I don't see why there would be significant resistance in creating a few more official diseases. In fact, there's progress being made in getting the FDA to allow for the development of anti-sarcopenia therapies. Also, individual SENS therapies will be used for specific diseases, not for "aging itself," because each therapy will target only one or at most a set of diseases rather than aging as a whole. For instance, beta-amyloid vaccines are used to try to alleviate Alzheimer's disease, not aging in general. The only real gain from defining aging as a disease might be for stuff like metformin that may slow aging but will never work well anyway (except for diabetes perhaps, the degree of slowing might be difficult to quantify for any single disease probably because the effect would so marginal but might be more significant across many diseases in total).

Posted by: Florin Clapa at November 19th, 2015 10:31 PM

"Since "aging" is just a convenient name for the diseases of aging, what's the point in engaging in what is essentially semantics?"

As Reason said, not being considered a disease makes funding very difficult.

"Also, individual SENS therapies will be used for specific diseases, not for "aging itself,"

True, but many of them are rare diseases. The amount of funding available for developing a treatment for a rare mitochondriopathy can't be compared to the funding for a treatment for aging, if it were considered a disease.

Posted by: Antonio at November 20th, 2015 2:15 AM

If SENS therapies were used and regulated only for individual diseases, does that mean we wouldn't end up with a comprehensive all in one package then? That's where I think the classification issue comes in maybe.

Posted by: Ham at November 20th, 2015 6:38 AM

Antonio, there's plenty of funding for the diseases of aging (just not some SENSible approaches to addressing them), and the purpose behind SENS isn't to develop cures for rare diseases (the rare mitochondriopathy stuff is incidental), so I'm not sure what you're trying to say.

Ham, at first, SENS therapies won't be applied as one package for various reasons. First, each therapy will need to be tested independently of the others to see if it works on its own. Since any therapy won't have a big effect on lifespan, it will necessarily have to be tested on specific diseases. If it doesn't work in people which already have a diagnosed disease (like beta-amyloid vaccines), then it could be tested in people which are at high risk of developing it to see if it can prevent it and/or be used in combination with other SENS therapies. The former scenario is exactly what's happening with beta-amyloid vaccines, and if these vaccines still won't work, they might be combined with therapies that get rid of tau. Since nearly everyone has a relatively high risk of developing every single disease of aging, SENS therapies will eventually be provided as a one preventative package.

Posted by: Florin Clapa at November 20th, 2015 6:29 PM

I've thought about this a while too, and it definitely seems to make sense to use overseas facilities for experimentation etc...

However, their are likely many talented researchers who don't want to live in a foreign country; so it's definitely still important to get the issue addressed here.

Perhaps progress overseas will embarrass the FDA beaurocrats enough to change direction? Wishful thinking perhaps...

Posted by: bmack500 at November 22nd, 2015 7:57 AM

Thank you, Reason. What is interesting is that one of the leading scientists at Novartis contributed to this article.

Here is another popular article on the subject:
https://www.newscientist.com/article/dn28531-label-ageing-as-a-disease-and-unleash-the-hunt-for-a-cure/

And there will be several influencers contributing to this research topic:
http://journal.frontiersin.org/researchtopic/3133/should-we-treat-aging-as-a-disease-academic-pharmaceutical-healthcare-policy-and-pension-fund-perspe

We need to get pension funds and insurance companies involved to make people realize the gravity of the aging problem.

Posted by: Biogerontology at November 23rd, 2015 1:31 PM

@biogerontologist

Those articles you linked on frontiersin.org were interesting. It's good to see more people want to intervene in the aging process. I just fear that the Kass mentality will continue to dominate.

Posted by: Ham at November 23rd, 2015 5:01 PM

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