“At the moment in medicine, we focus on treating individual diseases, such as cancer or heart disease, stroke or Alzheimer’s, all as siloed endeavours. But if we were able to treat the ageing process itself, which is the single biggest risk factor for any one of these diseases, then we could potentially prevent any one of them, simultaneously.” That’s the central thesis of the book physicist-turned-computational biologist Dr Andrew Steele is currently working on, focusing on the biology of the ageing process and the recent developments in science that are going to enable us to turn back the clock.
“There are fundamental biological processes that mean, as you get older, the chances of death or disease go up,” Andrew explains. “I’m interested in how we can intervene in those processes, slow them down or even reverse them.” He talks about ageing more in terms of risk – he defines it as the sum of the biological processes that put you at greater risk of disease as you get older. “There’s definitely a difference between chronological and biological age – some people do age better, and therefore have a lower risk of disease.”
Trendy Discussions Missing the Point?
Anti-ageing has become a popular thread of discussion in futurism circles for decades, but recently, there has been a boom in focused serious efforts to tackle ageing as a disease itself, and thus work towards a treatment to fend off the negative side effects, and the diseases that come with them, that ageing brings.
There’s a common query raised when the idea of extending life is discussed, which is: if we are to extend life, wouldn’t this mean that people would simply live longer as an older, possibly decrepit person?
Andrew explains: “Rather dismissively, and aloofly, some people in the research field call this the Tithonus Fallacy – it’s based on a Greek myth where a mortal called Tithonus falls in love with a goddess Eos, who then asks Zeus make him immortal so they can spend forever together. But she doesn’t ask for eternal youth, only eternal life.” Tithonus gets older and hence more debilitated and demented, babbling away so much that Eos eventually turns him into a grasshopper. (In Greek mythology, grasshoppers are eternal, and the myth provided an ‘explanation’ for why they chirrup incessantly, much like the stereotypical elderly man.) Steele continues: “It’s dismissive calling it a ‘fallacy’ as it’s something that people are genuinely concerned about. But what’s really interesting to a doctor is extending health, not extending life – so by treating the effects of ageing, you’re reducing the chances of getting these diseases, and therefore improving health.”
Emerging Science From the 60s
Andrew believes that the most promising area of development right now is in treatments to clear senescent cells. These cells were first observed in the 1960s by Leonard Hayflick who noticed that they stopped dividing after around 50 times, and then became large and globular – he named it the ‘senescent state’.
We now know that these senescent cells are created when troublesome cells, such as ones which are showing cancerous signs, don’t go into the suicidal cell state as they are meant to, and they accumulate over a lifetime. “Quite apart from the fact they’re just sat there doing nothing – they aren’t contributing to the structure or the function of the tissue – they also emit a load of bad molecules called the SASP (Senescent Associated Secretory Phenotype), which essentially accelerate the ageing process. The molecules are inflammatory, putting the immune system into overdrive, which drives aberrant processes going on in the body,” Andrew explains.
Interest was relatively stagnant until in 2015, when research showed that if you give mice drugs that destroy their senescent cells, they get biologically younger. Andrew says: “They get less cancer, their cataracts are reduced, they have thicker, glossier fur, and they even get more curious – a feature of younger mice is that if you put them in a maze, they’ll explore and find food, whereas older mice tend to be more hesitant – so across all these diverse measures, you can argue that ageing has been reduced.”
A Drug To Cure Ageing?
The researchers found a promising combination drug made up of Dasatinib, a chemotheraphy drug, and Querciten, a natural compound found in red fruit and vegetables.
“There’s quite a good case to be made that trials will happen in humans soon because Dasatinib is approved for chemotherapy and Querciten is a nutritional supplement with a known safety profile, so should be relatively quick to implement,” Andrew explains. However, considering it’s the first combination found – no one has ever looked for something like this in the history of medicine, no drug company has, as far as we know, looked for something that eradicates senescent cells – it is still just a first attempt.
But there are wider issues beyond the experimental nature of new science, Andrew explains. “The FDA doesn’t currently acknowledge ageing as an endpoint, so when these senolytic drugs are trialled, it will almost certainly be for specific conditions.” One condition that is currently being targeted as part of a trial for clearing senescent cells is osteoarthritis in the knee, which biotech startup Oisin Biotechnologies is conducting. “One of the reasons the knee was chosen is because it is a little sack of fluid which means you can inject stuff in a relatively isolated part of the body, and easily monitor side effects.” The big questions are of course whether it works, and then how to translate those findings for this one condition, into the broader realm of ageing. “How do you prove to the FDA or whatever other body you’re with that you’ve reversed ageing? There’s no accepted biomarker yet to benchmark results against, for example,” Andrew tells us.
Getting to Why
Of course it’s a compelling pitch for investors looking for a platform technology – one that has the potential to start ‘ticking off’ conditions beyond osteo arthritis – but for Steele, it’s less about creating a drug to treat illness. “I’d like to be able to give it to people who aren’t showing signs of ill health, I think that’s where the real potential of this stuff lies. The problem with elderly patients, is that they almost always have multiple things wrong with them and their bodies are negatively affected for a variety of diagnosable and undiagnosble reasons – it’s one of the fundamental reasons why our disease-centric approach doesn’t work.” Andrew believes the real potential would be realised in giving these drugs to people decades before they’re even showing symptoms – if you clear the senescent cells, an adjacent cell might not end up becoming cancerous, and you’ve stopped the problem before it even started. It also might mean that treatments end up being significantly less invasive and unpleasant because you’re not intervening at a late stage.
There’s of course a compelling case to be made about the money saved if the focus of healthcare moves from cure to prevention: “The money side is astonishing. The cost of cancer, heart disease, dementia and stroke to the economy, if you look at the direct cost of care and the indirect costs of people giving up work to look after their relatives, is over £800 per person per year in the UK. If you multiply it by 65 million – the population of the UK – that is a lot of money. And that’s just a subset of the diseases of the aged.”
For Andrew, though, it all comes back to a simple reason why he believes working on ageing is so important: “Of the 150,000 people around the world who die every day, about 100,000 of them die from diseases caused by ageing. That means of the tens of millions of lives that are lost per year, two thirds have had years, maybe decades, of suffering before death – not to mention the indirect suffering of relatives. I would argue that ageing is the single biggest cause of human suffering.”