Interview for VitaDAO
Barry Bentley
Reader (Associate Professor) in Bioengineering | Fulbright Scholar | PhD, FHEA, FRSB
I recently gave a short interview for VitaDAO , published in their Longevity Research Newsletter and copied below. VitaDAO is a vibrant decentralised organisation that is innovating how ageing research is funded and supported, and it was an honour to introduce our work to their community. In the interview, I discuss the consortium to classify ageing-related pathologies, our first consensus meeting, my journey into longevity research, and some broader thoughts on the field of ageing research.
What inspired you to enter longevity research?
I have been fascinated and unsettled by ageing, probably for as long as I have been aware of ageing as a concept; however, I can pinpoint the exact moment I became interested in longevity as a topic of scientific research. In early 2006 I was travelling around China and teaching English on a gap year before starting university. One night, I found myself in a dimly lit internet café on the outskirts of Wenzhou city, where I was browsing through forums on science and technology to pass the time. I stumbled across a link to an article discussing the Methuselah Foundation , which led me down the rabbit hole into the world of ageing research. The prospect of slowing or even reversing biological ageing was and still is a radical idea, sounding, to some, like a concept straight out of science fiction. The realisation that there were people who were seriously working on such a seemingly intractable problem captured my imagination. I already knew at that point that I wanted to become a research scientist, but that was the nudge that shifted my focus to the biological sciences, and ultimately led to my current career.
Which of the current theories of ageing do you think are the most convincing?
Each theory has its proponents, and various degrees of evidence supporting them. With the incredible progress that has been made in developing robust epigenetic clocks, the field seems to have shifted in favour of programmed theories of ageing in recent years. With how complex biology is, and how much is still unknown, I personally think it would be a mistake to commit to any one view or theory of ageing at this point; in fact, I would not be surprised if we find that all of the main theories are true to varying extents, with ageing being a highly heterogeneous process. To inelegantly coin a phrase: I suspect there is more than one way to age a cat.
How has the field changed since you started?
The biggest change has undoubtedly been the amount of interest in the field, and consequently, the amount of investments now being made in longevity research. Whether that is because the problems of an ageing population are finally starting to become too profound to ignore, or the science has reached a level of maturity that is finally investible, society as a whole is starting to take note.
What mistakes do you think the longevity field has made?
Until recently, the longevity field – as distinct from the broader field of ageing research – had serious credibility issues, which it still has yet to completely rid itself of. Starting as a fringe area, it unfortunately became associated with some questionable groups: unscrupulous people selling snake oil, biohackers doing questionable self-experiments, and futurists who were making predictions with little consideration for the realities of research. The field did a poor job of distancing itself from the more unsavoury ideas and actors. The strength of the science now speaks for itself, but reputational damage remains.
What advice would you give to people currently working in longevity research?
Like all areas of research, the main advice I would give is to be open minded. We do not yet know which approaches will be required to effectively slow or reverse ageing – there is just too much that we don’t yet know. To make progress, we’ll need to continue asking questions, trying new approaches, and robustly challenging our assumptions.
You were awarded an Impetus grant to explore how ageing should be classified. Why is this important?
That’s a great question. Before I answer, let me give some context to how the project came about: In 2016 and 2017, my collaborator, Dr Stuart C. , and I were discussing our frustrations that even though the scientific understanding of ageing was rapidly improving, the science was not filtering down to the bedside to influence the way patients were treated. Part of the reason for this, we realised, was due to clinical classifications.
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The World Health Organization (WHO) maintains a standard list of clinical codes, known as the International Classification of Diseases (ICD), which are used as the standard terminology by all WHO member states. These are used for recording diagnoses and treatments, for statistical and epidemiological purposes, for healthcare resourcing, approving clinical trials, medical billing, and so on – in short, they are at the core of virtually everything that happens within a health system.
Unfortunately, classifications for ageing-related changes are extremely limited in the ICD, which limits the ability to accurately describe and address ageing-related pathologies. As the idiom goes: you can’t manage what you don’t measure; and the ICD does not currently have the capacity to describe, and thus measure, ageing-related pathologies. Some groups have proposed to work around this by classifying ageing itself as a disease, but not only is this contentious, it also fails to address the heterogeneous nature of ageing – different organs and tissues age in different ways, and I believe we need the ability to capture this.
We had initial success in getting ageing recognised as a cause of disease by the WHO in 2019 [1], following which we published a large multi-author paper in Science proposing a consortium to develop a comprehensive and systematic classification system for ageing-related pathologies [2]. Norn Group thankfully saw the value in this, and awarded us an Impetus Grant to make it a reality. So far, we have recruited approximately 300 experts, who we are working with to develop these new classifications.
You recently hosted a consensus meeting to define the criteria for an ageing-related pathology, could you give us the highlights of this meeting?
This was the first meeting of the consortium to develop the classifications for ageing-related pathologies. Of course, to develop those classifications, it is essential that the consortium members have agreement on what constitutes an ageing-related pathology – so this was the main goal of the first meeting: to define the criteria that will allow us to differentiate an ageing-related pathology from others. We had a wide range of input from clinicians and scientists, but there was pretty much unanimous support for three criteria that were proposed: Firstly, that the damage must develop or progress with increasing age; that it should be associated with, or contribute to, functional decline or increased susceptibility to functional decline; and that, for the purposes of clinical classification, it must be based on evidence from studies in humans.
Our consortium coordinator, Dr Emma Short , who is a consultant histopathologist and research associate, did a brilliant job of chairing the meeting, and is working on writing-up the outcome of the discussions, which we will be publishing in the near future.
Is ageing a disease?
There is little agreement amongst gerontologists on how to classify ageing, mainly because ageing is such a catch-all term that refers to many things: biological age, as a sociological status or marker, chronological advancement, appearance, etc. Personally, I think the debate is somewhat counterproductive. Regardless of how we use the term, and whether we call it a disease, the fact remains that people become sicker as they get older. My own approach is to focus on those aspects that make people sick: the underlying ageing-related pathology.
What are you currently working on in the lab?
In addition to my work classifying age-related pathology, I am fortunate to have received a Fulbright Award, which is enabling me to work at Harvard Medical School and Massachusetts General Hospital this year on the development of new technologies for the cryopreservation of cells, tissues, and organs. It has been an ambition of mine for a long time to make contributions in this area, so it’s exciting to finally be making that a reality.