The Science Behind Improving Life Expectancy
Scientists have embarked on a quest to eliminate ageing and extend life expectancy indefinitely. This post from The Guardian encapsulates the recent work being done for extending ‘healthspan’, the years that are free of frailty and disease.
Fixing the ‘problem’ of ageing is the mission of Silicon Valley, where billions is pouring into biotech firms working to ‘hack the code’ of life – despite concerns about the social implications…
In Palo Alto in the heart of Silicon Valley, hedge fund manager Joon Yun is doing a back-of-the-envelope calculation. According to US social security data, he says, the probability of a 25-year-old dying before their 26th birthday is 0.1%. If we could keep that risk constant throughout life instead of it rising due to age-related disease, the average person would – statistically speaking – live 1,000 years. Yun finds the prospect tantalising and even believable. Late last year he launched a $1m prize challenging scientists to “hack the code of life” and push human lifespan past its apparent maximum of about 120 years (the longest known/confirmed lifespan was 122 years).
Yun believes it is possible to “solve ageing” and get people to live, healthily, more or less indefinitely. His Palo Alto Longevity Prize, which 15 scientific teams have so far entered, will be awarded in the first instance for restoring vitality and extending lifespan in mice by 50%. But Yun has deep pockets and expects to put up more money for progressively greater feats. He says this is a moral rather than personal quest. Our lives and society are troubled by growing numbers of loved ones lost to age-related disease and suffering extended periods of decrepitude, which is costing economies. Yun has an impressive list of nearly 50 advisers, including scientists from some of America’s top universities.
Yun’s quest – a modern version of the age old dream of tapping the fountain of youth – is emblematic of the current enthusiasm to disrupt death sweeping Silicon Valley. Billionaires and companies are bullish about what they can achieve. In September 2013 Google announced the creation of Calico, short for the California Life Company. Its mission is to reverse engineer the biology that controls lifespan and “devise interventions that enable people to lead longer and healthier lives”. Though much mystery surrounds the new biotech company, it seems to be looking in part to develop age-defying drugs. In April 2014 it recruited Cynthia Kenyon, a scientist acclaimed for work that included genetically engineering roundworms to live up to six times longer than normal, and who has spoken of dreaming of applying her discoveries to people. “Calico has the money to do almost anything it wants,” says Tom Johnson, an earlier pioneer of the field now at the University of Colorado who was the first to find a genetic effect on longevity in a worm.
In March 2014, pioneering American biologist and technologist Craig Venter – along with the tech entrepreneur founder of the X Prize Foundation, Peter Diamandis – announced a new company called Human Longevity Inc. It isn’t aimed at developing anti-ageing drugs or competing with Calico, says Venter. But it plans to create a giant database of 1 million human genome sequences by 2020, including from supercentenarians. Venter says that data should shed important new light on what makes for a longer, healthier life, and expects others working on life extension to use his database. “Our approach can help Calico immensely and if their approach is successful it can help me live longer,” explains Venter. “We hope to be the reference centre at the middle of everything.”
In an office not far from Google’s headquarters in Mountain View, with a beard reaching almost to his navel, Aubrey de Grey is enjoying the new buzz about defeating ageing. For more than a decade, he has been on a crusade to inspire the world to embark on a scientific quest to eliminate ageing and extend healthy lifespan indefinitely (he is on the Palo Alto Longevity Prize board). It is a difficult job because he considers the world to be in a “pro-ageing trance”, happy to accept that ageing is unavoidable, when the reality is that it’s simply a “medical problem” that science can solve. Just as a vintage car can be kept in good condition indefinitely with periodic preventative maintenance, so there is no reason why, in principle, the same can’t be true of the human body, thinks de Grey. We are, after all, biological machines, he says.
His claims about the possibilities (he has said the first person who will live to 1,000 years is probably already alive), and some unconventional and unproven ideas about the science behind ageing, have long made de Grey unpopular with mainstream academics studying ageing. But the appearance of Calico and others suggests the world might be coming around to his side, he says. “There is an increasing number of people realising that the concept of anti-ageing medicine that actually works is going to be the biggest industry that ever existed by some huge margin and that it just might be foreseeable.”
Since 2009, de Grey has been chief scientific officer at his own charity, the Strategies for Engineered Negligible Senescence (Sens) Research Foundation. Including an annual contribution (about $600,000 a year) from Peter Thiel, a billionaire Silicon Valley venture capitalist, and money from his own inheritance, he funds about $5m of research annually. Some is done in-house, the rest sponsored at outside institutions. (Even his critics say he funds some good science.)
De Grey isn’t the only one who sees a new flowering of anti-ageing research. “Radical life extension isn’t consigned to the realm of cranks and science fiction writers any more,” says David Masci, a researcher at the Pew Research Centre, who recently wrote a report on the topic looking at the scientific and ethical dimensions of radical life extension. “Serious people are doing research in this area and serious thinkers are thinking about this .”
Although funding pledges have been low compared to early hopes, billionaires – not just from the technology industry – have long supported research into the biology of ageing. Yet it has mostly been aimed at extending “healthspan”, the years in which you are free of frailty or disease, rather than lifespan, although an obvious effect is that it would also be extended (healthy people after all live longer).
“If a consequence of increasing health is that life is extended, that’s a good thing, but the most important part is keeping people healthy as long as possible,” says Kevin Lee, a director of the Ellison Medical Foundation, founded in 1997 by tech billionaire Larry Ellison, and which has been the field’s largest private funder, spending $45m annually. (The Paul F Glenn Foundation for Medical Research is another.) Whereas much biomedical research concentrates on trying to cure individual diseases, say cancer, scientists in this small field hunt something larger. They investigate the details of the ageing process with a view to finding ways to prevent it at its root, thereby fending off the whole slew of diseases that come along with ageing. Life expectancy has risen in developed countries from about 47 in 1900 to about 80 today, largely due to advances in curing childhood diseases. But those longer lives come with their share of misery. Age-related chronic diseases such as heart disease, cancer, stroke and Alzheimer’s are more prevalent than ever.
The standard medical approach – curing one disease at a time – only makes that worse, says Jay Olshansky, a sociologist at the University of Chicago School of Public Health who runs a project called the Longevity Dividend Initiative, which makes the case for funding ageing research to increase healthspan on health and economic grounds. “I would like to see a cure for heart disease or cancer,” he says. “But it would lead to a dramatic escalation in the prevalence of Alzheimer’s disease.”
By tackling ageing at the root they could be dealt with as one, reducing frailty and disability by lowering all age-related disease risks simultaneously, says Olshansky. Evidence is now building that this bolder, age-delaying approach could work. Scientists have already successfully intervened in ageing in a variety of animal species and researchers say there is reason to believe it could be achieved in people. “We have really turned a corner,” says Brian Kennedy, director of the Buck Institute for Research on Ageing, adding that five years ago the scientific consensus was that ageing research was interesting but unlikely to lead to anything practical. “We’re now at the point where it’s easy to extend the lifespan of a mouse. That’s not the question any more, it’s can we do this in humans? And I don’t see any reason why we can’t,” says David Sinclair, a researcher based at Harvard.
Reason for optimism comes after several different approaches have yielded promising results. Some existing drugs, such as the diabetes drug metformin, have serendipitously turned out to display age-defying effects, for example. Several drugs are in development that mimic the mechanisms that cause lab animals fed carefully calorie-restricted diets to live longer. Others copy the effects of genes that occur in long-lived people. One drug already in clinical trials is rapamycin, which is normally used to aid organ transplants and treat rare cancers. It has been shown to extend the life of mice by 25%, the greatest achieved so far with a drug, and protect them against diseases of ageing including cancer and neurodegeneration.
A recent clinical trial by Novartis, in healthy elderly volunteers in Australia and New Zealand, found a variant of the drug enhanced their response to flu vaccine by 20% – our immunity to flu being something that declines with old age.
“[This was] the first [trial] to take a drug suspected to slow ageing, and examine whether it slows or reverses a property of ageing in older, healthy individuals,” says Kennedy. Other drugs set to be tested in humans are compounds inspired by resveratrol, a compound found in red wine. Some scientists believe it is behind the “French paradox” that French people have a low incidence of heart disease despite eating comparatively rich diets.
In 2003, Sinclair published evidence that high doses of resveratrol extend the healthy lives of yeast cells. After Sirtris, a company co-founded by Sinclair, showed that resveratrol-inspired compounds had favourable effects in mice, it was bought by drug giant GlaxoSmithKline for $720m in 2008. Although development has proved more complicated than first thought, GSK is planning a large clinical trial this year, says Sinclair. He is now working on another drug that has a different way of activating the same pathway.
One of the more unusual approaches being tested is using blood from the young to reinvigorate the old. The idea was borne out in experiments which showedblood plasma from young mice restored mental capabilities of old mice. A human trial under way is testing whether Alzhemier’s patients who receive blood transfusions from young people experience a similar effect. Tony Wyss-Coray, a researcher at Stanford leading the work, says that if it works he hopes to isolate factors in the blood that drive the effect and then try to make a drug that does a similar thing. (Since publishing his work in mice, many “healthy, very rich people” have contacted Wyss-Coray wondering if it might help them live longer.)
James Kirkland, a researcher who studies ageing at the Mayo Clinic, says he knows of about 20 drugs now – more than six of which had been written up in scientific journals – that extended the lifespan or healthspan of mice. The aim is to begin tests in humans, but clinical studies of ageing are difficult because of the length of our lives, though there are ways around this such as testing the drugs against single conditions in elderly patients and looking for signs of improvements in other conditions at the same time. Quite what the first drug will be, and what it will do, is unclear. Ideally, you might take a single pill that would delay ageing in every part of your body. But Kennedy notes that in mice treated with rapamycin, some age-related effects, such as cataracts, don’t slow down. “I don’t know any one drug is going to do everything,” he says. As to when you might begin treatment, Kennedy imagines that in future you could start treatment sometime between the age of 40 and 50 “because it keeps you healthy 10 years longer”.
With treatments at such an early stage, guesses as to when they might arrive or how far they will stretch human longevity can only be that. Many researchers refuse to speculate. But Kirkland says the informal ambition in his field is to increase healthspan by two to three years in the next decade or more. (The EU has an official goal of adding two years to healthspan by 2020). Beyond that, what effects these drugs might have on extending our healthy lives is even harder to predict. A recent report by UK Human Longevity Panel, a body of scientists convened by insurer Legal and General, based on interviews with leading figures in the field, said: “There was disagreement about how far the maximum lifespan could increase, with some experts believing that there was a maximum threshold that could not be stretched much more than the current 120 years or so, and others believing that there was no limit.”
Nir Barzilai, director of the Institute forAgeing Research at the Albert Einstein College of Medicine, is one of the pessimists. “Based on the biology that we know today, somewhere between 100 and 120 there is a roof in play and I challenge if we can get beyond it.” Venter is one of the optimists. “I don’t see any absolute biological limit on human age,” he says, arguing that cellular immortality – in effect running the clock backwards – should be possible. “We can expect biological processes to eventually get rid of years. Whether this will happen this century or not, I can’t tell you”. Such ideas are just speculation for now. But John Troyer, who studies death and technology at the Centre for Death and Society at the University of Bath, says we need to take them seriously. “You want to think about it now before you are in the middle of an enormous mess.”
What happens if we all live to 100, 110, 120 or beyond? Society will start to look very different. “People working and living longer might make it more difficult for a new generation to get into the labour force or find houses,” says Troyer. And, with ageing delayed, how many children are we talking about as being a normal family? “There is a very strong likelihood there would be an impact on things like family structures.” A 2003 American president’s Council on Bioethics reportlooked at some of these issues suggesting there may be repercussions for individual psychology, too.
One of the “virtues of mortality” it pointed out is that it may instill a desire to make each day count. Would knowing you had longer to live decrease your willingness to make the most of life? De Grey acknowledges potential practical challenges but cheerily says society would adapt, for example by having fewer children, and with people able to decide when to end their lives. There are pressing questions too about who would benefit if and when these interventions become available. Will it just be the super rich or will market incentives – who wouldn’t want it? – push costs down and make treatment affordable?
Will Britain’s NHS or health insurers in other countries pay for drugs that extend peoples lives? The medical cost of caring for people in their twilight years would fall if they remained healthier longer, but delayed ageing will also mean more people draw pensions and state benefits. But advocates say these challenges don’t negate the moral imperative. If the period of healthy life can be extended, then doing so is the humanitarian thing to do, says Nick Bostrom, director of Oxford’s Future of Humanity Institute. “There seems to be no moral argument not to,” he says. Troyer agrees but asks whether living longer does necessarily mean you will be healthier – what does “healthy” or “healthier” mean in this context? he asks.
The far future aside, there are challenges for the new tech entrants. Calico may get too side-tracked by basic research, worries de Grey; Venter’s approach may take years to bear fruit because of issues about data gathering, thinks Barzilai; while the money on offer from the Palo Alto prize is a paltry sum for the demanded outcome and potential societal impact, says Johnson. Still, history reminds us, even if they don’t succeed, we may still benefit.
Aviator Charles Lindbergh tried to cheat death by devising ways to replace human organs with machines. He didn’t succeed, but one of his contraptions did develop into the heart-lung machine so crucial for open-heart surgery. In the quest to defeat ageing, even the fruits of failure may be bountiful.
Tech billionaires who want to make death an elective
Why might tech zillionaires choose to fund life extension research? Three reasons reckons Patrick McCray, a historian of modern technology at the University of California, Santa Barbara. First, if you had that much money wouldn’t you want to live longer to enjoy it? Then there is money to be made in them there hills. But last, and what he thinks is the heart of the matter, is ideology. If your business and social world is oriented around the premise of “disruptive technologies”, what could be more disruptive than slowing down or “defeating” ageing? “Coupled to this is the idea that if you have made your billions in an industrial sector that is based on precise careful control of 0s and 1s, why not imagine you could extend this to the control of atoms and molecules?,” he says.
Peter Thiel
Peter Thiel, 47, PayPal co-founder and Facebook’s first investor, recently told Bloomberg Television he took human growth hormone (HGH) as part of his regime to reach 120 (there is no evidence it works and it can even cause harm). He also follows a Paleo diet, doesn’t eat sugar, drinks red wine and runs regularly. He has given more than $6m to Aubrey de Grey’s Sens Foundation, dedicated to extending the human lifespan. In a recent interview he identified three main ways to approach death. “You can accept it, you can deny it or you can fight it. I think our society is dominated by people who are into denial or acceptance, and I prefer to fight it.”
Sergey Brin
Google co-founder Sergey Brin, 41, is known for his love of special projects like Google Glass and CEO Larry Page has credited him for helping bring its new biotech company Calico to fruition. “We’re tackling ageing, one of life’s greatest mysteries,” says the website of the research and development company launched in 2013 and which in September 2014 joined with biopharmaceutical firm AbbVie to pour up to $1.5bn into a research facility focused on fighting age-related diseases. An extra reason for Brin’s interest may be that he discovered in 2008 he carries a genetic mutation that gives him a greater likelihood of developing Parkinson’s disease. Bryn’s wife is co-founder of personal genomics company 23andMe.
Larry Ellison
Larry Ellison, co-founder of computer company Oracle, told his biographer Mark Wilson. “How can a person be there and then just vanish, just not be there?” Ellison, 70, created the the Ellison Medical Foundation in 1997 to support ageing research and has spent more than $335m in the area, though it announced in 2013 that it would no longer fund further grants in the area. Ellison remains tight lipped about why, but there are reports that, with the emergence of Calico, he felt that he’d done his bit.
Craig Venter
“A lot of people spend their last decade of their lives in pain and misery combating disease,” says Craig Venter, San Diego based pioneering biologist and billionaire entrepreneur who raced to sequence the human genome. “I think it is possible to begin to do more about that than we are doing.” Venter, 68, announced his new company, Human Longevity, to promote healthy ageing using advances in genomics and stem cell therapies in March 2014. Would Venter like to beat death? “I am not sure our brains and our psychologies are ready for immortality,” he says. “[But] if I can count on living to 100 without major debilitating diseases I would accept that Faustian bargain right now.”
Dmitry Itskov
A digital copy of your brain turned into a low-cost, lifelike avatar, which doesn’t age. That’s the vision of Dmitry Itskov, a thirtysomething Russian multi-millionaire internet mogul who founded an online media company New Media Stars. His 2045 Initiative, so-called for the year he hopes to complete it, aims to “create technologies enabling the transfer of a individual’s personality to a more advanced non-biological carrier, and extending life, including to the point of immortality”. Though not from Silicon Valley himself, his ideas draw on those of Ray Kurzweil, a prominent futurist, who is director of engineering at Google. Kurzweil has predicted that scientists will one day find a way to download human consciousness, no longer necessitating the need for our bodies.
Source: Live forever: Scientists say they’ll extend life ‘well beyond 120’ | Science | The Guardian
