Live for ever: Scientists say
they’ll soon extend life ‘well beyond 120’
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- 2016 MANY New Advances towards LONGEVITY
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 cos are
bullish about what they can achieve. In Sept 2013 Google announced the creation
of Calico, short for the California Life Co. 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 co, 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 Univ 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 co 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, theStrategies
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.)
Aubrey de Grey is chief scientific officer of
his own charity, the Strategies for Engineered Negligible Senescence (Sens)
Research Foundation. He funds about $5m of research annually. 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 Univ 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.”
American biologist and technologist Craig
Venter whose company Human Longevity Inc plans to create a database of a
million human genome sequences by 2020.
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 co 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 showed blood 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 for Ageing 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 report looked 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 likeGoogle 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.
How Silicon Valley is trying to cure ageing
Death has always been considered one of life's only real certainties,
but now some of the world's top scientists are challenging the assumption
Scientists believe that ageing is simply a medical problem for
which a solution can be found Photo: Alamy
By Josie Ensor, San Francisco
8:31PM GMT 14 Feb 2015
Humanity
has long been in search of the mythical Fountain of Youth, from Alexander the
Great to knights of the Crusades.
But now
Silicon Valley scientists believe they are on the cusp of discovering the cause
of ageing, which will help them achieve the unthinkable: find a cure.
Earlier
this year, doctor and investor Joon Yun launched the Palo Alto Longevity Prize,
offering $1 million (£650,000) to anyone who could “hack the code of life” and
come up with a way to keep us young.
“It’s
always been said that there’s two certainties in life: death and taxation, but
death isn’t looking so certain anymore,” says Stuart Kim, one of 50 world-class
advisers on the prize board and a professor in Developmental Biology and
Genetics at Stanford University.
He
believes ageing is simply a medical problem for which a solution can be found.
The
prize will be awarded to the first team to unlock what many believe to be the
secret to ageing: homeostatic capacity, or the ability of the body's systems to
stabilise in response to stressors.
As the
body ages, being able to recover from diseases, injuries and lifestyle stresses
becomes more difficult. In youth, blood pressure and elevated blood sugar
levels can return easily to normal levels.
As
homeostatic capacity erodes as we get older, the body is no longer able to
regulate these changes as effectively, resulting in diseases such as diabetes
or hypertension.
Dr Yun,
who worked for several years as a radiologist at Stanford Hospital before
joining a hedge fund investing in health care, uses the analogy of a
"weeble wobble" toy to explain that no matter how far it is pushed,
it is able to centre itself again.A
person only becomes aware of their body's homeostasis when they start losing it
in middle age: often characterised by the loss of ability to tolerate cold or
hot weather, or feeling nauseous after a roller-coaster ride where you once
felt exhilarated.
"Up
until about 45 years old, most people die from external stressors such as
trauma or infection, but as we get older we die of what looks like a loss of
intrinsic capacities," he tells The Sunday Telegraph.
Increased
homeostatic capacity could allow people to live beyond 120 years – the
theoretical maximum human lifespan.
Scientists
could effectively slow down the body's clock and enable us to remain middle
aged for 50 years or more, meaning we can feel 50 when we are really 80. The
future could see us not just living longer, but staying healthier for longer.
"This
isn't like plastic surgery where you're papering over the cracks, this is
actually making a person younger from the inside out," Dr Yun says.
The
first half of the prize will be awarded next year to the team that can restore
the homeostatic capacity of an ageing adult mammal to that of a young one,
thereby reversing the effects of ageing.
The
second half to the team that can then extend the lifespan of their chosen
mammal by 50 per cent of published norms.So far
15 teams have entered, including a handful from Stanford University as well as
from further afield at the genetics department at George Washington University
in DC and the Albert Einstein College of Medicine, New York.
But
they face even fiercer competition outside the prize. Google recently unveiled
its own $1.2 billion research centre Calico, or the California Life Company,
aiming to achieve the tech giant's boldest ambition yet – extend the human
lifespan. While
their work, which is led by Arthur Levinson, former CEO of biotech firm
Genentech, is shrouded in secrecy, they are said to be focusing on developing
drugs for age-related neurodegenerative disorders.
"Our
goal is to make progress on a very basic challenge: how to help people stay
healthier for longer," Mr Levinson said of the project.
Meanwhile,
Craig Venter, the geneticist who sequenced the first human genome, has set up
his own company, Human Longevity Inc., alongside stem cell pioneer Robert
Hariri.
They
plan to sequence one million human genomes, including those of several
supercentenarians, in order to build the world's largest database of human
genetic variation. By looking at the DNA, they hope to discover a common
feature among those living longer.
Dr de
Grey, a British gerontologist at the SENS Foundation in Silicon Valley, has
dedicated his life's work to solving the perennial problem of death. He
believes it should be treated as a disease and can be postponed indefinitely.
"Since
the dawn of civilisation, humanity has been enslaved by the knowledge that no
lifestyle choice, no medicine, no quirk of fate, can enable anyone to live for
more than a few decades without suffering a progressive decline that leads inevitably
to death," the Cambridge University researcher says.
"But
scientists have already drawn a road map to defeat biological ageing and will
one day show there is no such inevitability. This is a when, not an if."
The
idea of reverse-engineering ageing is not a new one. The American Academy of
Anti-Ageing Medicine was set up in 1992, but only recently has the idea gained
traction in mainstream medicine.
Dr Yun
believes there had not been the support or funding needed to galvanise the
field until now. "No one was incentivised to fix the underlying causes of
ageing as too many of the big players in the medical and insurance industries
benefit from the current system," he says.
There
has also not been much of a public appetite, which scientists put down to lack
of understanding. A recent survey by Pew Research found that most Americans did
not actually want to live beyond the accepted human lifespan.
When
asked if they wanted medical treatments that slowed the ageing process and
allowed the average person to live to at least 120 years, 56 per cent surveyed
said no. When asked how long they wanted to live, the median answer was 90.
Even
Bill Gates, Microsoft founder and philanthropist, seemed to write off the
desire to extend life as Silicon Valley hubris. "It seems pretty
egocentric while we still have malaria and TB for rich people to fund things so
they can live longer," he said, while in the same Q&A admitting that
the last thing on his bucket list was "to not die".
Along
with the reasoning that it felt "fundamentally unnatural", a number
of survey respondents said they would worry about overpopulation and a
potential lack of resources.
But Dr
Yun says society will adapt to changes in life expectancy. "Just a few
generations ago it was common to see people going into the workforce at 13, and
dying before they turned 45. Things have changed since then – people now stay
in education for longer, and have children and retire much later. "Plus
if people begin living longer, they will care more about what the world will
look like in the future – impact concerns will shift from being their
children's problem to being their problem."
Life-extending
technology has become a booming industry in Silicon Valley.
Google
X and Proteus Digital Health are among a dozen or so companies working on
"ingestible tech" that they hope will go some way towards keeping us
alive and healthy for longer. Google's
pill, which is filled with tiny iron-oxide nanoparticles that enter the
bloodstream, is able to identify cancer tumour cells, which give off early
biochemical signals when they contract the disease. Proteus,
having already gained FDA approval, is now in talks with Britain's National
Health Service about the possible use of its sensor pill, which sends
biological information it retrieves from the body to a smartphone.
At the
same time, the XPrize Foundation, a charity that runs technology competitions,
is working on developing a hand-held all-in-one diagnostic device. With one
drop of blood, the "tricorder" will be able to accurately detect
conditions such as diabetes and tuberculosis as well as measuring blood
pressure and temperature – all from the comfort of your home.
Grant
Campany, director of the XPrize, told The Sunday Telegraph: "It will all
but eradicate the need to see a doctor for check-ups. The device will help
people take their health back into their own hands."
The
Longevity Prize's Dr Kim, who has spent the last 10 years looking into the
causes of ageing, believes we cannot afford not to come up with a solution.
"We shouldn't just be thinking of how to treat diseases like cancer, we
should be looking at how to prevent them by figuring out why old people are much
more likely to get them," he says. "If you could take 80-year-olds
and make them biologically more like 60-year-olds, that's a 15-fold decrease in
the rate of cancer right there.
"If
we solve this, we all win."
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