Do we have to age? – The Guardian

When the biologist Andrew Steele tells people his thoughts on ageing that we might one day cure it as if it were any other disease they are often incredulous and sometimes hostile. Once, at a friends wedding, he left a group of guests mildly incensed for suggesting that near-future humans might live well into their 100s. A similar thing happens at dinner parties, where the responses are more polite but no less sceptical. He understands the reaction. We think of ageing as an inescapable fact of life were born, we grow old, so it goes. Thats been the narrative for thousands of years, he says, on a video call. But what if it didnt have to be?

Steele began professional life as a physicist. As a child, he was fascinated by space, the way many scientists are. But he has spent the past three years researching a book about biogerontology, the scientific study of ageing, in which he argues the case for a future in which our lives go on and on. Steele considers ageing the greatest humanitarian issue of our time. When he describes growing old as the biggest cause of suffering in the world, he is being earnest. Ageing is this inevitable, creeping thing that happens, he says. He is wearing a button-down shirt and, at 35, a look of still-youthful optimism. Were all quite blind to its magnitude. But what do people die of? Cancer. Heart disease. Stroke. These things all occur in old people, and they primarily occur because of the ageing process.

Steele defines ageing as the exponential increase in death and suffering with time, and he thinks it would be helpful to finally grapple with this raw quantity of suffering. The human risk of death doubles every seven or eight years. We tend to breeze through the first five or six decades of life relatively unscathed, health-wise. Maybe we wake up at 50 with an ache, or slightly sagging skin, but still we are generally considered unlucky if we discover a tumour or develop arthritis or suffer heart problems. The death of a 50-year-old from disease is a premature death.

But at some point in our 60s a kind of cliff edge appears, and often we have no choice but to stumble over it. Easy movements become hard. We begin to lose our hearing and our sight. Frustrating and embarrassing things start to happen. Why cant I feel the tips of my toes? What on earth has happened to my hip? The body has worked tirelessly for years, and the cumulative internal effects of that action the problematic buildup of aged, senescent cells; the dangerous mutations of other cells; the steady decline of the immune system; the general wearing-down of the bodys structures suddenly predispose us to a variety of age-related diseases: cancer, cardiovascular disease, hypertension, dementia. A 10-year-olds risk of death is 0.00875%. At 65, the risk has risen to 1%. By the time we turn 92 we have a one in five chance of dying that year. For decades we are mostly fine, Steele says, and then, all of a sudden, were not.

The dream of anti-ageing medicine, Steele writes in his book, Ageless: The New Science of Getting Older Without Getting Old, is treatments that would identify the root causes of dysfunction as we get older, then slow their progression or reverse them entirely. These root causes are what biogerontologists call hallmarks. Cancer isnt a hallmark of ageing, Steele says now. But its caused by several of the hallmarks of ageing. If scientists can address those hallmarks, we can come up with treatments that slow down the whole ageing process, deferring diseases into the future.

The hope isnt that we get to live longer for the sake of it, it is that we live longer in good health. Some people call this longevity; Steele refers to increasing a persons healthspan. Theres this misconception when you talk to people about treating ageing, he says. They imagine theyre going to live longer but in a state of terrible decrepitude, that youre going to extend their 80s and 90s so theyre sat in a care home for 50 years. That doesnt make sense from a logical perspective or a practical one.

I say, What would be the point?

Exactly!

Its just more pain

Nobody would want it, he says. Then he raises an eyebrow. Its surprising that people would actually think scientists would want that.

Humans have been searching for a cure for ageing for thousands of years. Herodotus wrote of the Fountain of Youth in the 5th century BC; countless people have made lengthy, futile quests for life-extending elixirs. Until recently, very little was known about why we age and how. For a long time, scientists looked at it and thought, Oh God, this is going to be some immeasurably complex process that we cant possibly hope to study in a lab, Steele says, which dissuaded research. Until the 1960s, it was generally accepted that our role on this Earth was to produce children, and that once wed succeeded in that undertaking, our bodies, fulfilled of function, would be left to slowly fade.

But in the past three decades biogerontological research has accelerated, and recent successes have sparked excitement. A 2015 study, published by the Mayo Clinic, in the US, found that using a combination of existing drugs dasatinib, a cancer medicine, and quercetin, which is sometimes used as a dietary suppressant to remove senescent cells in mice reversed a number of signs of ageing, including improving heart function. A 2018 study that used the same drugs found that the combination slowed or partially reversed the ageing process in older mice. In another study, the drug spermidine extended the lifespans of mice by 10%, and studies using the drug rapamycin have extended the healthspans of mice, worms and flies, though it comes with problematic side-effects, including the suppression of the immune system and the loss of hair. Last year, scientists in Texas transplanted stem cells from young mice into elderly ones, adding three months to their average lifespans, which in equivalent human terms could be worth more than a decade.

To Steele this is all thrilling. The pace of change has been dizzying, he says of recent developments. Though it is the fact that human trials have begun that excites him most. After the success in mice, the first trial aimed at removing senescent cells in humans began in 2018, and others are ongoing. A more recent study found that a combination of hormones and drugs appears to help rejuvenate the thymus, which contributes to the immune system but degenerates rapidly with age. Next year, a landmark trial will begin to investigate whether metformin, a drug used to treat diabetes, might in fact delay the development or progression of age-related chronic diseases such as heart disease, cancer and dementia.

In Ageless, Steele writes, This collection of evidence is tantalising, and foreshadows a future where ageing will be treated. He also writes: This future may not be far away. When I ask him what he means by not far away, exactly, he smiles. Scientists are rightly sceptical, he says, but its important to say that a lot of significant breakthroughs could happen in the lifespan of people alive today.

I ask, Can you be more specific?

Eventually, he says, I think we are very likely to have a drug that treats ageing in the next 10 years.

Steele believes we will be hopelessly unlucky if scientists dont make a breakthrough within that time, given how many human trials are in progress or upcoming. And although these breakthroughs wont result in treatments that extend our lives by 100 years, they will give us enough extra time to ensure were alive for subsequent breakthroughs, subsequent treatments, subsequent additions in lifespan and so on. Our lives will be extended not all in one go but incrementally one year, another year, suddenly were 150. In Ageless, Steele talks of a generation of people that grows up expecting to die but, thanks to an accumulation of new treatments, each more effective than the last, just doesnt. One after another, he writes, lifesaving medical breakthroughs will push their funerals further and further into the future.

What Steele is talking about isnt immortality; people will continue to die. Science wont help if, looking down at your phone, you walk out into the road and get hit by a car. Or if you fall off a ladder and break your neck. Or if you are unlucky enough to be hit by a missile in a war zone. Or if you contract a virulent infectious disease that has no vaccine. But it will result in lifespans that are significantly longer than what we currently consider normal.

I ask if Steele expects there to someday be lots of 150-year-olds wandering around, as healthy as 20-year-olds.

Yes, he says, if it all works.

I say, 200-year-olds playing football in the park?

Why not? he says. The trouble is, saying were going to have 150-year-olds walking around looking like 20-year-olds, its weird. It sounds sci-fi. It sounds a bit creepy. Ultimately, I dont want this because I want to have a load of 150-year-olds looking like 20-year-olds, I want it because those 150-year-olds wont have cancer, they wont have heart disease, they wont be struggling with arthritis. Theyll still be playing with their grandkids, their great-grandkids even. Its about the health and lifestyle benefits.

When Steele brings up his work with people, the question he gets asked most often is: What about overpopulation? He has a go-to answer he thinks highlights the ridiculousness of the question. Imagine were staring down the barrel of 15bn people on Earth, he says. There are lots of ways to try and tackle that problem. Would one of them be: invent ageing?

That he is asked this question so frequently frustrates him. More so, he is bothered by the implication that what he is suggesting is somehow weird or inhuman or unholy, rather than ultimately helpful for society. If Id just written a book about how were going to cure childhood leukaemia using some amazing new medicine, he says, literally nobody would be like, But isnt that going to increase the global population?

He shakes his head.

What Im saying is, Here is an idea that could cure cancer, heart disease, stroke Curing any one of those things would get you plaudits. But as soon as you suggest a potentially effective way of dealing with them altogether, suddenly youre some mad scientist who wants to overpopulate us into some terrible environmental apocalypse?

Steele considers this a major hurdle in biogerontologys potential success our incredible bias toward the status quo of ageing as an inevitable process, and our inability to accept it as preventable. If we lived in a society where there was no ageing, and suddenly two-thirds of people started degenerating over decades, started losing their strength, started losing their mental faculties, and then succumbing to these awful diseases, it would be unthinkable. And of course, wed set to work trying to cure it.

He makes reference to the pandemic. The coronavirus exemplifies the problem we have in terms of funding science, in trying to confront these kinds of challenges. Because its so acute, because it all of a sudden appeared on the scene and the entire global economy was dragged to a halt, we see this very clear, current, present need to do something about it. And yet if you look at ageing, or even climate change, these are slow-moving disasters, and so theyre easy to miss. It is not lost on him that ageing-related drugs might have reduced the impact of the coronavirus, given it is a disease that is particularly life-threatening among older populations. To this end, he thinks biogerontology will eventually dramatically change the role of medicine, from being primarily reactive to primarily preventive. Weve somehow unintentionally drifted into this state in society where we end up treating endpoints, almost in a state of panic, at the last minute, he says, rather than preventing them beforehand.

Steele considers Ageless a call to arms, and is hopeful it presents enough evidence to finally convince the public as well as regulators, who currently dont define ageing as a disease, which makes it difficult to receive support for trials that ageing is a problem to be fixed. There is a kneejerk reaction to biogerontology, just because it sounds strange, he says. We place ageing research in this separate category socially, morally, ethically, even scientifically. When, actually, its just an extension of the normal goals of modern medicine.

Writing a book on ageing, it turns out, is a good way to make you reappraise your own lifestyle. These days, Steele is running more than he used to, and he has begun to watch what and how much he eats. Its not like I was ever a massive couch potato, he says. But, equally, I have tried to optimise things. In the absence of anti-ageing drugs, he suggests we all do the same. It seems that a lot of the sort of basic health advice that everyone can recite do some exercise, dont be overweight, try to eat a broad range of foods, dont smoke all that stuff basically slows down the ageing process.

I tell him Ive spoken to people who are taking several unproven supplements a day, hoping to eke out a few more years, and of others who, ahead of the trial, are already taking the experimental drug metformin.

Given that Im in my 30s, he says, I think the case against metformin is stronger than the case for. The evidence is suggestive, but its not conclusive. And theres a spectrum. There are people who are experimenting with senolytics. There was the case of the biotech CEO who went to Colombia and had gene therapy. But the data in humans just isnt there. He adds: The same is true of so many of these supplements and health foods. If any of these things did have a substantial effect, wed know about it.

When I ask him what he thinks of the anti-ageing industry all of those creams and serums that promise rejuvenation, our modern-day elixirs he says, Id like to completely obviate it. If the breakthroughs do come, they are likely to significantly change the structure of our time on Earth. We are used to the three-act life: we are young and learn, we are middle-aged and work, we are old and retire. But what happens if we live another 100 years? Might we go back to school at 60, or switch careers at 105 or, at 40, decide to take some kind of 20-year soul-searching hiatus, knowing well have a century or more to do other things having returned from whatever wilderness we had run away to?

And what about death? At one point during our conversation, I ask Steele if he imagines a time when dying becomes a choice. He thinks the question is overblown. Because death is inevitable people have rationalised it as something that drives life, or gives life meaning, or adds some sort of poetry to the human condition, he says. But I think, broadly speaking, death is bad. If there was less death in the world, I think most people would agree that was a good thing. And though my passion for treating ageing isnt driven by reducing the amount of death, its driven by reducing ill health in later life, its driven by conquering disease, its driven by getting rid of suffering, if theres less death as a side-effect? I dont think thats a bad thing.

Ageless: The New Science of Getting Older Without Getting Old by Andrew Steele is published by Bloomsbury at 20. Buy it from guardianbookshop.com for 17.40

The root causes of ageing are called hallmarks. Treat these and you slow ageing.

1. Genomic instability As we age, we accumulate genetic damage. Simply, over time, our DNA gets mangled. It is thought that if scientists can find a way to repair that damage, they will then be able impact the ageing process.

2. Cellular senescence The longer we live, the more chance we have of experiencing a build-up of senescent (old) cells, which tend to hang around in the body and can contribute to the onset of age-related diseases.

3. Mitochondrial dysfunction Mitochondria are organelles that generate the energy our cells need to power necessary biochemical reactions. It has been found that mitochondrial dysfunction can accelerate ageing.

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Do we have to age? - The Guardian