Eric Le Bourg has published a thought-provoking paper in Biogerontology that offers a critique of geroscience [1].
Geroscience, we need to talk…
When people discuss the prospects of targeting the aging processes to prevent, halt, or even reverse age-related diseases, their beliefs often fall into two opposing categories. The first is overly optimistic blue-sky thinking, and the second is an overly pessimistic view that it is simply impossible.
Both extremes are problematic: one side largely ignores the challenges involved, but the other side discounts the progress being made by the professionals working in the field. What is needed is a balanced view that accepts the difficulty of the task ahead but does not outright dismiss the possibilities.
The author of this paper is not opposed to the idea of tackling the aging processes but offers some valid criticism of the field as it stands. His aim is to actually offer critique, not because he thinks the field is nonsense, but rather because he wants to see it mature and be taken seriously.
What is geroscience?
“Geroscience” is a simple term; “gero” means “old age”, so geroscience refers to the science of aging. Geroscience operates on three basic principles:
- The goal is to improve the quality of life in humans.
- Age-related diseases are the primary challenge towards reaching that goal.
- Aging is the main risk factor for those diseases, so slowing or reversing aging may delay or prevent multiple diseases at once.
While some people see it as an attempt to rebrand life extension, rejuvenation biotechnology, anti-aging, and so on, the word has become more popular lately, particularly in academic circles. Nevertheless, the author of the paper makes some valid points relating to geroscience.
Healthspan vs. lifespan
The author points out that there seems to be debate in the geroscience field that it is possible to increase healthspan without increasing lifespan. This seems unlikely, and others have criticized this apparent disconnect.
Blagosklonny proposes that the goal of geroscience is the extension of lifespan by extending healthspan [2]. This is in contrast to most current medicine, which focuses on tackling one disease at a time. Medicine today does a great job of extending your lifespan but not your healthspan. In other words, you can medically manage an age-related disease and remain alive for many years while still being sick.
However, extending healthspan without extending lifespan seems quite unlikely. This is because geroscience interventions do not seek to simply treat and manage the symptoms of age-related diseases; rather, they seek to slow or even reverse the actual aging processes themselves.
It is difficult to grasp how someone could instantly transition from being healthy to dead in a world where aging is partially under medical control. It is likely that compression of morbidity would occur in such a scenario and that the diseases of aging would be pushed back further into advanced old age. This would most likely also increase lifespan as well as healthspan.
However, if aging were comprehensively understood and interventions could fully control it, then there would naturally be no limit to healthy human lifespan. This is with the understanding that if medicine could fully suppress the diseases of aging, then aging itself would also be effectively suppressed.
While it is unlikely that such comprehensive control of aging would occur as the result of initial geroscience interventions, it is perhaps a longer-term possibility as the field, technology, and effectiveness of interventions are refined.
Over-enthusiasm is harmful
Our field has a reputation for being tall on promise and short on delivery, and this could continue to be a problem. The author of the paper points out that there are quite a number of publications that hint that we are close to a breakthrough in slowing or even reversing human aging.
This is a fair point, and indeed, there are a number of researchers, companies, journalists, and bloggers who continue to support the narrative that the defeat of aging is just around the corner. This is misleading, and such ambassadors for the field would do well to curb over-enthusiasm and present a more realistic and balanced view of where we are now and the challenges ahead.
For example, there is currently a lot of enthusiasm for partial cellular reprogramming as a way to rejuvenate the body. While the animal studies so far have been promising and there has been a flood of investment into this approach, there is a lot of work to be done before it reaches people. We are most likely decades away from it reaching us, assuming that things go well and it translates.
The same applies to senolytics; there was once a huge amount of hype and enthusiasm for senescent cell-destroying technologies. Stories in the media would have had us believe that effective senolytic-based treatments were going to be available in short order, yet here we are, years later and we are still waiting.
This is because as it turns out, senescent cells do have necessary functions and are not as black and white as their initial portrayal, and simply destroying them all is probably not a good idea. Work is ongoing to study, understand, and categorize these cells so that they can be targeted in an optimal way.
In it for the long haul
It is dangerous to apply reductionist thinking to complex things like aging, and it happens all too often. We should be thinking about progress in the context of decades, not months. Biology and the development of medicine is a slow process, and we still have a long road to reach our ultimate goal.
The fact of the matter is that while considerable progress has been made in animal studies regarding the reversal of aging, the increase of lifespan and healthspan, and the rejuvenation of tissues and organs, those results are a long way from translation to humans.
The work of our field is very much a long haul, and we should always be mindful of that, especially when talking to other people about it.
Abstract
The geroscience field hypothesises that it could be possible to delay all age-related diseases by delaying the ageing process itself, and not by curing each age-related disease individually. While this perspective is attractive, some issues provisionally prohibit to fully adhere to it, such as the risk for some over-enthusiasm or scientism and the tendency to accept that results observed in animal models can be easily translated in human beings. Particularly, it is not clear whether geroscience plans to delay or suppress ageing, or if healthspan could become very close to lifespan. This article lists some of these issues, in the hope that supporters of geroscience will grasp them to allow a full development of the field, and argues that geroscience should avoid reductionist approaches not taking into account social and behavioural complex aspects of human ageing.
[…] this article does not argue that new breakthroughs in biology, medicine, and technology will be unable to delay ageing, or, on the contrary, that these breakthroughs will make healthspan becoming very close to lifespan, which could also increase up to the current maximal lifespan, or even higher: time will tell. However, it is argued that colleagues supporting the ‘‘optimistic side’’, the geroscientists, should take care to clarify some issues of the geroscience field, and this article has listed some.
Even if some colleagues are dubious about the eventual success of the geroscience initiative, the best move is maybe to say ‘‘let a hundred flowers bloom’’ until geroscientists bring to the fore positive results. If they fail, it will be one of the innumerable failures of science, if they succeed, even partly, it will be a major result towards a better knowledge of the ageing process.
Conclusion
The author goes on to highlight further issues with the geroscience approach as it currently is, and this paper is worth a read. While some of it is probably not going to be palatable for people who have unrealistic hopes for things to move faster than they really are, it is important that we remain grounded and consider the real situation when we talk about the field.
Geroscience is a great concept, and it could potentially be a game changer. However, it has some image and technical issues that really need to be addressed before things can move forward.
Literature
[1] Le Bourg, E. (2022). Geroscience: the need to address some issues. Biogerontology, 1-6.
[2] Blagosklonny, M. V. (2021). The goal of geroscience is life extension. Oncotarget, 12(3), 131.
5 Comments
Donovan
February 10, 2022
Personally, I think this decade (2020-2030) will see proof of concept that aging can (or cannot) be targeted in humans (slowed down and reversed) via general clinical trials (TAME/PEARL. ..) or clinical trials targeting a disease or a particular organ (Turn.bio / SENISCA…) even if of course it will take decades for these interventions to be used (and democratized) in humans.
Steve Hill
February 10, 2022
I absolutely agree with you Donovan. It will be getting through clinical trials and taking it to mainstream healthcare use that will be the time killer IMO. My intent here in writing was to be grounded but not pessimistic about the timescale.
Neil
February 17, 2022
I have to admit, I have been torn on how to respond to this article. First, I agree that promising complete control in months is ridiculous and laughable. In fact, we probably won’t have complete control even in 2-3 decades. But, I do think we have very good reasons for expecting a smattering of huge successes in 2-3 decades time. Each won’t be the final thing, but added together, they will begin to push the boundary. Then, with each passing decade, they will push it further and further, so that, on average, our lifespan will begin receding from us rather than approach. This will occur before complete control is achieved.
The exponential nature of technology is hard for us to intuit because our long evolution occurred during times with imperceptible change during a single generation. However, now each generation is seeing gigantic changes within their lifetimes and each new generation sees even greater magnitude of change.
This is hard to see when we look at the daily articles posted here and elsewhere as most of them are the ordinary, but important, science that slowly moves the field forward. However, what it misses is all the improvements occurring in the supportive technology. Computational power is growing exponentially. As it does, the algorithms improve and take better advantage of the computational power. As this occurs, new tools are created that wash over the field when they finally reach the transition point. Think of AlphaFold for example. With all the properly-folded proteins, researchers can now design proteins. And, along with this, researchers are starting to work on computation that can simulate interactions between a protein and another molecule and so on. This will vastly improve over the coming decades.
But, it isn’t only computer power. Many have rightly pointed out that we can’t make progress without the biology and that is true. But, the tools we use to do biology are also improving exponentially. Once again, the day-to-day reports just don’t show the true nature of what is happening. Many, many technologies in many fields all contribute until finally they reach a tipping point that a profound new tool washes over the field that significantly increases the efficiency of each experiment. This allows the researchers to do much more than they could before. We had a speaker come to my institution recently who talked about the technology of reading a single strand of DNA on a chip. A single strand was pulled through a small channel and each base pair was read as it passed. It blew me away! Compare that with the very beginning of the human genome project back in the 90’s. Gigantic improvement in efficiency and cost. This is happening over and over in biology and all these tools add up to create new tools.
However, considering these great changes still misses the point because it might lead us to believe that we will see the same amount of change in the next 30 years as we did in the last 30 years. But, the fact is, we will see much, much more. All these tools support the creation of new tools that are even more powerful. We are not building the new tools with the old tools of the 90’s. We are instead building the new tools with the tools we have now. It is like compounding interest. Each month you get interest on your current balance, not on the balance that you had when you first opened the account.
But, finally, to the point about whether rejuvenation technology is “just around the corner”. My claim is that it is. I claim that 2,3 or 4 decades is just around the corner. Consider the fact that life has been evolving for several billions of years, …, humans have been around for a couple hundred million years, civilization has been around for tens of thousands of years, humans have wondered whether they could be rejuvenated and have searched for it for thousands of years. And, now, after all this, we are now at the doorsteps of rejuvenation. Not months, of course, but so what in the long history of life and humankind. Decades is barely a blink in the grand scheme of thing. The fact that it is even possible at all that significant rejuvenation could occur in our lifetime is beyond amazing. Even if it doesn’t happen in time for me, I would still consider it around the corner if it happened anytime this century, and it will.
Neil
February 18, 2022
I meant humans have been around for a couple hundred thousand years. It’s not meant to be exact, just order of magnitude.
Walter Crompton
February 28, 2022
“The author points out that there seems to be debate in the geroscience field that it is possible to increase healthspan without increasing lifespan. This seems unlikely, and others have criticized this apparent disconnect.” I think this is based upon a slight misunderstanding. Most everyone would agree that extending healthspan would usually increase lifespan, but many would claim that such an upgrade in healthspan often results in a trivial increase in lifespan; not none at all.
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