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The science of defying death

Scientists are working against the clock to discover how we can live longer, healthier lives – and how we might one day defeat the most common causes of death.
The science of defying death

IT’S BARELY 8AM on a spring morning in Sydney’s inner south-west. Already the indoor ice rink is alive with lithe figures swooping and twirling in the cool internal air. These world-class figure skating hopefuls have been here for hours, practising their gravity-defying leaps, forcing themselves to their feet after each brutal tumble.

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At age 74, with a bald head and white beard, Richard Lynch seems out of place – until he gets on the ice. His coach watches from the sidelines as Richard glides, spins and jumps to the passionate strains of Khachaturian’s Spartacus. At one point he stumbles and falls onto the glistening white ice…and my heart stops. A fall in a typical 74-year-old could mean a hip fracture, hospitalisation, joint replacement or immobility. In some 74-year-olds, even a knock against a piece of furniture would be enough.

Richard sits on the ice for a moment, and then pushes himself to his feet and skates on. “I’ve done enough of that in my day,” he says later. “I’ve had injuries and surgery, and so on, and back problems from falling.” Does it worry him? “No, it doesn’t. I really don’t think about it actually,” he says.

Richard could be at home, reading a large-print book, contemplating a slow morning during which the most strenuous activity would be getting up out of an overstuffed chair to put on the kettle. Instead, he’s training at the Canterbury Olympic Ice Rink four mornings each week. He has the Australian national championships coming up. He’s also working towards reclaiming his number-one title at an international figure skating competition in Germany later this year.

And it’s clear the agile Richard is not only equipped with skill, but also a sense of humour: during training he dons his favourite T-shirt – a tight black number with ‘NOT DEAD YET’ emblazoned across the front.

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Mary Whitehurst , 110, is Australia’s oldest person. She was born in the Welsh village of Maerdy on New Year’s Day 1905. She’s lived since 2007 in a care facility in Sunbury, Victoria, where she entertains residents with daily piano recitals. “I have had a big life, a long life… I am thankful, very thankful,” Mary says, advising “you must get up and get doing”.

WE ARE LIVING longer than ever before. Most Australians can expect to live about 83 years, which puts us comfortably in the global top 10. But it’s not enough just to defy death for those few extra years. We want to be alive, active and defiantly healthy until our last breath.

Some, such as Richard Lynch, achieve this. But others are less fortunate, and have their senior years cut short by heart disease, stroke, dementia, cancer or any number of other afflictions that medical technology cannot yet cure. The scientific quest for a longer, healthier life – and ultimately defeating death – has become one of the grand challenges of our time. And if there was ever a starting point for such a quest, it would be the heart.

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Heart disease is the number-one killer in Australia and globally; in 2013, it claimed the lives of more than 11,000 Australian men and 8750 Australian women. Coronary heart disease is the slow strangulation of the heart’s oxygen supply as the vessels bringing blood to the muscles of the heart are narrowed and ultimately blocked by the build-up of fatty plaques.

When enough of the heart muscle dies due to lack of oxygen, the heart cannot pump enough oxygenated blood around our body, and we die.

But what if we were able to circumvent heart disease – would that mean an instant increase to the length of most people’s lives?

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Professor John Fraser, cardiac specialist at Brisbane’s Prince Charles hospital, brings together experts from all over the country, and the world, to work on developing a fully contained artificial heart that could take over from a failing biological one.

PROFESSOR JOHN FRASER’S artificial heart lab at Brisbane’s Prince Charles Hospital looks more like the plumbing aisle in a hardware store. Intensely focused young researchers hunch over a bench strewn with lengths of clear plastic hose, containers of water and an assortment of pipes and valves.

The centrepiece of their attentions is a large device consisting of several upright plastic tubes filled with water. The liquid pulses up and down in the tubes, accompanied by pneumatic hisses and clicks. It’s a mechanical representation of the human heart, designed to mimic the behaviour and problems and issues of a failing one. It exists so John and his team of engineers, cell scientists and doctors can design, build and test artificial hearts they hope will one day entirely replace their organic counterparts.

At the moment, the best solution we have got for a dying heart is called a ventricular assist device, a mechanical pump that steps in for the weakened left ventricle of the heart. “All it’s really doing is using the old heart almost like a porch,” John explains, waving around a contraption that looks as though it came from under the hood of a car.

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“The blood pours into the old heart and it acts as a place that the blood can funnel through, go into the ventricular assist, get spun around and get spurted out.”

The pump is an electromagnetically suspended spinning disk, powered by a cable that comes out through the chest wall and connects to a battery pack, usually contained in a bum bag. That cable is the device’s greatest weakness, because it offers an entry point by which bacterial infection can bypass the body’s defences. “Once that link is infected, that’s your last good day on earth,” John says.

Ventricular assist devices are built to support either one side of the heart or the other. A left and a right ventricular assist device can be used simultaneously, but nothing yet exists that combines the functions of both in one system.

The Holy Grail for John – and many other specialists and researchers like him around the world – is an implantable artificial heart powered by energy that can be transmitted across the skin without compromising its integrity. “This technology does exist but it isn’t ­optimised yet – there will be a coil inside the skin, and there will be a coil outside the skin.” The energy transfer between the coils needs to be optimised so it’s enough to power the device without damaging the skin.

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He thinks we’ll have such a device in 10 years. There are already several promising contenders around the world, such as the SynCardia and AbioCor devices, the latter of which includes energy transmission across the skin. But John says the perfect artificial heart won’t be cheap. “Do we want the ‘six million dollar man’? Because it’s not going to be a six million dollar man, it’s going to be a sixty million dollar man,” he says.

Despite building a successful career and international reputation in the field of artificial hearts, John argues passionately for prevention rather than cure.

“It’s kind of opposing what I do, but if you can put $1 into healthy lifestyles, it will save – I don’t know the number – maybe $30?”

In fact, the Australian Institute of Health and Welfare recently argued that the $810 million spent on anti-smoking, physical activity and other programs to tackle heart disease from the 1970s to the 1990s resulted in savings of something like $9.3 billion to the healthcare sector.

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“I’m looking forward to the zeros,” says eternal optimist Agnes Marshall, 98, who’s about to enter her second century of life. “I think it will be an exciting time!” She attributes her good health to lots of fruit, vegetables and whole grains, daily exercise and having “something to look forward to every day”.

PREVENTION IS MUCH less sexy than a titanium heart. But Australia’s top five killers – heart disease, dementia, stroke, lung cancer and chronic obstructive pulmonary disease – are all, at least partly, and in some cases mostly, preventable.

If you were going to start anywhere in trying to extend your life, Professor Kaarin Anstey would suggest quitting smoking. “Smoking increases the risk of cancers, heart disease, dementia and lung disease,” says Kaarin, director of the Centre for Research on Ageing, Health and Wellbeing in Canberra. Studies suggest long-term smokers sacrifice at least 10 years of life expectancy. But given smoking rates are inching downwards towards 10 per cent, nine in 10 of us are already on that wagon. So what else? “It’s diet and exercise,” says Kaarin, with a laugh. “It always comes back to those two.”

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Predictable? Yes. Trivial? Not according to the authors of an article published 10 years ago in the New England Journal of Medicine. In a strident call to arms, a group of American medical experts warned that the current generation of young people was on track to be the first in a millennium to have a shorter life expectancy than their parents. And they have pointed an accusing finger squarely at obesity.

“So far we haven’t seen a decrease in life expectancy but it’s certainly a logical possibility from the unhealthy lifestyles particularly associated with the Western diet and obesity,” Kaarin says. The solution is simple. Don’t fuss about whether to go the Atkins route, paleo, macrobiotic or whatever the latest fad diet is. Just eat your vegies. “If you look at the literature, the thing that is most consistent, across every diet and every study, is that vegetables are the healthiest food,” Kaarin says. “They will prevent disease and you’ll live longer if you eat more leafy green vegetables.”

Kayoko Suzuki, 62, is not who you’d typically expect to find in a pole-dancing fitness class, doing upside-down ‘pencil’ positions. But her partner bought her a voucher in 2009 and she is now a regular at the Sydney studio where she takes her classes. “I like physical exercise,” Kayoko says, “… but also mentally it made me stronger.”

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Even caloric restriction – the idea that eating a low calorie diet will extend lifespan – has been shown to work in mice, but so far, the evidence for its benefits in humans is mixed. One theory suggests caloric restriction is the reason behind the famed longevity of Japan’s Okinawa islanders.

The other half of the prevention equation is physical activity, which Kaarin says is as close to a panacea as you can get. “It just has so many benefits and I think it’s probably under-recognised; even though we talk about it all the time, I think we still have an awful lot to learn about physical activity and the potential benefits.” You don’t need a gym membership and personal trainer. Kaarin says the simplest of strength training can be incorporated into daily life, like doing squats while washing up. But the benefits will be felt in muscle tone, stability, blood pressure, blood sugar levels, cholesterol levels and many other vital parameters.

But what if you’re one of the likely majority of older Australians who haven’t paid as much attention to the lifestyle warnings, and whose arteries are plagued with varying degrees of the atherosclerosis that could one day block them completely?

It might surprise you to know that we have extremely effective, safe, readily available treatments to prevent heart attacks. We’ve had them for quite a long time. The problem is, we’re not very good at taking our medicine. Research suggests as many as half the people who are prescribed drugs, which if taken successfully will drastically reduce their risk of a first or repeat heart attack, don’t take them.

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The question of why occupies a good amount of Professor Stephen MacMahon’s time. As co-founder and principal director of The George Institute for Global Health in Sydney, he is interested in how to get people to take the medicine that would almost certainly extend their life.

“The combination of drugs that we’ve studied in the various research projects that we’ve done have been proven to reduce the risk of a heart attack or stroke by a minimum of 50 per cent and possibly as much as 75 per cent,” Stephen says. “That is as close as you’re going to get to a cure in terms of chronic disease.”

The drugs in question are aspirin, a cholesterol-lowering statin and two blood pressure-lowering drugs. They’re all relatively cheap – having come off patent years ago – relatively safe and incredibly effective. The problem with getting anyone to take four different tablets at least once a day, especially if they’re feeling healthy, is that invariably they don’t.

Thus was born the idea of the polypill, a tablet that combines fixed doses of these four drugs into one pill, taken once a day. One study by The George Institute and researchers around the world showed such a simple change meant more than 40 per cent more people took their medication as they were supposed to. These were people who had either had a heart attack, or were very likely to have one by virtue of their risk factors, such as high blood pressure, high cholesterol, smoking or diabetes.

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Stephen believes there is a strong case for anyone with a high risk of cardiovascular disease – even if they haven’t actually had a heart attack – being put on such a polypill. “A way that patients often find it useful to assess the potential value to them is to say, ‘What’s your heart age?’ and that basically is what’s your risk of having a heart attack for your age group,” he says.

Lifestyle change, especially quitting smoking, can reduce your heart age, but Stephen says changes in diet and exercise can only go so far. “There is no question, if you want to change your heart age, this is a very effective way to do it.”

For someone with a 1-in-5 chance of having a heart attack in the next 5–10 years, which qualifies them as high risk, a polypill such as this could buy them 10 or even 20 years.

And this is not the only polypill being considered; others are being trialled, with different combinations of blood pressure- lowering agents or including a dose of folic acid to reduce levels of the amino acid homocysteine, which is linked to a range of diseases including heart disease and cancer.

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But a polypill is designed only to reduce the risk of dying from heart disease. What if we had a pill that could extend life not by preventing one or another disease, but by acting on the mechanisms of ageing at a much more fundamental level?

These drugs are not only real; they are also already widely used in humans. What’s strange about this is that the drugs are used to treat other diseases, and it is only recently that their anti-ageing effects have been discovered.

One of these is the immuno-suppressing drug rapamycin. Since 1999, it has been used to suppress the immune system of patients receiving kidney treatments, and to prevent cardiac stents from getting overgrown with tissue. Then, in 2005, researchers found that it extended the lifespan of yeast cells and, in 2009, studies showed it did the same for mice – in the case of female mice, they lived on average 14 per cent longer than those not given the drug. The effect hasn’t yet been studied in humans, but it’s the closest thing we have to an anti-ageing drug so far.

A FATAL HEART attack or heart failure might kill the greatest number of Australians, but ask many older people what they fear most about ageing, and they will say it’s the slow theft of their mind. Dementia and Alzheimer’s disease are the second leading cause of death in Australia, although they don’t make the top 10 globally.

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Unfortunately, there is no polypill for dementia, no gleaming steel replacement for a brain rendered functionless by a mysterious degeneration we are yet to visualise, let alone diagnose.

Geriatrician and researcher Dr Eamonn Eeles is one of many on the frontline of the dementia war, trying to understand the enemy’s tactics and counter them. A big part of the challenge of dementia and Alzheimer’s disease is diagnosing them early enough that the few drugs we do have offer the best chance of benefit.

“At present no imaging modality will tell us the diagnosis of dementia or not – it’s really a clinical diagnosis,” says Eamonn, from The Prince Charles Hospital in Brisbane. But if we had a way to look at the brain and pick out the characteristic features of Alzheimer’s disease, that might help us not only diagnose it early, but identify people whose disease is more likely to respond to current treatments.

“At the moment we say ‘You’ve got dementia, try this and see how you go’, and we can’t really be more specific than that,” says Eamonn. “We know that about one-third of people respond anyway, but about 10 to 15 per cent have good responses for up to three years, which is quite positive. So if you can identify those, and hit them hard, that would be a benefit.”

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When Betty, 89, met vegetarian Milton, 93, more than 70 years ago, her family of proud butchers gave her six months to live. “It was a different time, of course,” Betty says. Seven decades, 11 children (four adopted), 40 grandchildren and 57 great-grand-children later, the couple are still going as strong as ever. They regularly meet friends for a 6am swim in the Currumbin Creek Estuary on Queensland’s Gold coast.

But what about preventing it in the first place? The risk factors for Alzheimer’s disease and dementia have lifestyle elements in common with heart disease – smoking, diet, high cholesterol and high blood pressure. And once again, up pops physical activity.

“Exercise has been shown to be the thing that one can do to try and reduce your risk or delay onset of Alzheimer’s disease, and it’s not entirely certain why; although new nerve production, improved blood flow and an increase in the size of the memory part of the brain – the hippocampus – are implicated,” Eamonn says. Research suggests that people who exercise regularly still develop the classic physiological features of Alzheimer’s disease – the dreaded amyloid plaques – but are less likely to show the clinical symptoms of the disease.

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Exercising the mind could also help reduce the risk, or at least delay the onset of Alzheimer’s symptoms. “Being multilingual at an early age is thought to be protective, and education is thought to be protective as well,” says Eamonn. But this doesn’t necessarily mean that so-called brain training does help, although Eamonn says it can’t do any harm.

“There are a lot of people attending late-life education from, for instance, the [Sydney-based] University of the Third Age,” he says. Socialisation also may have a protective effect, Eamonn says, particularly as people with dementia often isolate themselves from family, friends and community services.

All this would be good news to John Hunter, who’s one of a growing number of senior entrepreneurs, or ‘seniorpreneurs’, making their mark in the business landscape, working their brains hard and being social at the same time.

“I think anybody who gets to my age and hasn’t got a flood of ideas hasn’t been paying attention,” Hunter says.

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Despite being in his 70s, Hunter regularly attends a dedicated workspace in Hawthorn, managed by the SeniorPreneurs Foundation. “At my time of life I know what to do but not how to do it, so the SeniorPreneurs Foundation is an enabler in the sense that it’s providing a platform or framework where we can collaborate and do things together that we can no longer do alone.”

So you’ve lived a life of moderation, exercised regularly, stayed away from cigarettes, used your brain and engaged with your social community. Does that mean you’ll live forever?

Professor Rob Brooks, an evolutionary biologist at the University of New South Wales, has successfully tripled the lifespan of crickets.

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THE CRICKET TRYING valiantly to escape from Professor Rob Brooks’s clutch is a native Australian variety. It’s probably most famous for its call, which is perfect for movie sound effects. But it is also serving as a neat illustration for why picking your parents carefully is the dark secret of longevity.

“We’ve made lines of crickets that live about three times as long as usual and we’ve made ones that live half as long as usual,” says Rob, director of the Evolution and Ecology Research Centre at the University of New South Wales. The selective breeding of these longer- and shorter-lived crickets is in aid of a project examining how changes in diet affect fitness and lifespan, but Rob says it shows just how big a role genes play in lifespan.

What’s even more interesting is that these genes are often tied to reproductive success. There is a genetic trade-off that means that crickets experiencing greater reproductive success earlier in life tend not to live as long once their mojo has disappeared.

“What we were showing really is that the genetic variation that influences reproduction influences lifespan so genes that cause males to call a lot and early on in adulthood also cause them to die sooner,” Rob says.

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Whether this ‘live fast, die young’ phenomenon plays such a big role in humans is up for debate, but Rob says there is evidence that genes predisposing people to conditions such as Alzheimer’s disease and breast cancer later in life may have benefits in reproductive fitness ­earlier in life.

If anyone was likely to know the secret to a long life, it would be the rare individual who manages to make it to 100 years of age. Australia is home to about 4000 centenarians – more than three-quarters of whom are female.

Dr John McCormack has studied centenarians for years, but even he doesn’t claim to know the answer to such longevity.

“In terms of giving you the secrets to longevity, there are as many secrets as there are people,” says John, from La Trobe University. “Some will say that they’ve never drunk or smoked, others will say they have a nip of brandy.

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“Probably some of the common ones are that they’ve worked fairly physically hard, and they’ve been moderate in their diet and lifestyle.” His research shows genes are still the biggest clincher; long-lived parents or siblings are the strongest predictor that someone will live to extremely ripe old age. So is being 100 all it’s cracked up to be?

“Probably only about 10 per cent of the people I’ve interviewed said they didn’t want to continue on, that they’d had enough and were worn out,” John says.

Many have been forced to accept the limitations of extreme old age, such as the pianist who can no longer play complex pieces and must limit himself to simpler ones. But most are glad to be here. “I find people are remarkably honest in what they say; the clear majority in my little survey say that living to 100 is good and worth living.”

Bianca Nigrady is a science writer based in the Blue Mountains, where she indulges her love of science, writing and baking in equal measure. This is her first feature for AG.

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*Michael Amendolia likes storytelling through his photographs. A Sydney-based former News Ltd staff photographer, his last feature for the journal was Messages from Mungo (AG 123).8

This article originally appeared on Australian Geographic.*

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