Who wants to live forever?

We are living longer. How can we live better?

Your mother’s diet, your immune system and air pollution are among the many factors affecting how long you live and whether you develop Alzheimer’s or cancer. ERC researchers are unravelling the secrets of longevity, exploring ways of adding ‘life to years’ as well as ‘years to life’. (Hint: It helps to be a monk.)

Now the bad news: although they will live longer, they will not live better. Men born today will spend 17 of their years in poor health, and women will be ill 22 years. Hence the adage: ‘women are sicker but men die quicker’.

Nor is this un-healthy ageing problem a  European issue only. In rapidly developing nations such as China and India, life expectancy is also on the up – but so too are chronic conditions, including cancer, heart disease, diabetes and dementia. It seems we have added quantity of life without making much progress on quality.

How long will you stay healthy?

The European Commission has figured your odds, by EU member-state and gender, of a healthy lifespan. Yikes.

Is it worth extending lifespan if it only adds years of misery? Clearly not – but many are trying to do something about it. The European Union set a bold target in 2012: to increase the average healthy lifespan of Europeans by two years by 2020. And the European Research Council (ERC) with its bottom-up funding competitions is backing top scientists in their quest to figure out how we can live longer, better lives. Many of their findings are startling but can change the way you live.

(Spoiler alert: yes, you guessed it, diet and exercise are a big part of ‘health expectancy’ – but so is your parents’ age at the time of your birth and the strength of your immune system.)

‘Dementia tsunami’

King’s College London, United Kingdom

Developing dementia is one of our worst fears. More than 60 per cent of us think an Alzheimer’s diagnosis means ‘life is over’. While care has improved, there is still no cure.

Today, 47 million people live with dementia worldwide. That’s more than the population of Spain – and it’s getting worse. Fast. By 2050, this number is expected to hit 131 million as populations age.

What is dementia?

Dementia refers to a number of conditions that cause damage to brain cells. This leads to a long-term and often gradual decrease in the ability to think and remember, and can be associated with emotional and language problems.

Alzheimer’s disease is the most common cause of dementia. That’s why it is given the most attention by researchers. Other forms of dementia include vascular dementia which occurs when the blood supply to the brain is damaged; and dementia with Lewy bodies which shares characteristics with Alzheimer’s and Parkinson’s.

“We’re looking at a doubling of the numbers living with dementia every 20 years,” says Martin Prince, professor of epidemiological psychiatry at King’s College London. Prince is running an ERC-funded project which looks at ways of stemming the tsunami of brain diseases, such as Alzheimer’s, that too often accompany old age.

“Whether, in ageing societies, we can add ‘life to years’ as well as ‘years to life’ is an unresolved question,” he says.

Prince’s team has found the fastest growth in dementia patient numbers is in low and middle-income countries. His 10/66 Dementia Research Group takes its name from the fact that less than 10 percent of research on dementia is directed towards the 66 per cent of the population with dementia living in developed countries.

“We used to think that the prevalence of dementia in low-income countries was much lower than in high-income countries because survival to old age was less common,” he says. “Our research suggests this is not the case. Based on better data from China and Africa we can now say that dementia is much more likely than we had thought.”

Millions of people

The big challenge now is to look at why some people fare better than others when it comes to remaining compos mentis. “The trajectory of dementia growth rates could be changed by doing more to prevent onset of dementia, by modifying risk factors such as high blood pressure, diabetes and smoking,” Prince says. And for the millions who already have dementia, better care pathways are recommended while scientists continue to search for a cure.

Men vs. women: the great longevity race

Oesterreichische Akademie Der Wissenschaften, Austria

‘Women are sicker, men die quicker’: can nuns and monks solve the gender paradox?

 

As stated above, women live longer than men, yet bear the brunt of diseases such as osteoporosis and arthritis. One of the big questions for scientists interested in healthy ageing is why. The trouble is that with so many biological factors (such as genes and hormones) and lifestyles (smoking, diet, exercise and stress levels), it’s not an easy mystery to unravel.

Marc Luy at the Vienna Institute of Demography had a theory. He reckoned women are sicker not because they are female but because they are alive longer. Men would be just as sick if they weren’t dying off earlier.

Secondly, he suspected that grouping all diseases together might be misleading. Could it be that while women pick up more non-fatal chronic conditions, they have fewer life-threatening ailments such as heart failure? There may be a reasonable expectation for the so-called ‘gender paradox’: it might depend on how we define serious chronic disease.

Natural experiment

To test these hypotheses, Luy turned to a surprising source of natural experimental data – the monasteries and convents of Germany and Austria where, in some of the communities, the average age is more than 80 years.

“Normally it is hard to control for environmental factors and separate them from biological factors when comparing men and women,” he explains. “But people in cloistered communities live very similar lives regardless of gender.”

So Luy began trawling the archives of religious orders to find out how long monks and nuns live. Through the landmark ERC-funded HEMOX project, he has also surveyed almost 1,200 members of Catholic orders to find out how they live – the first holistic health surveys of their kind. Are cloister residents living with disease and disability? How would they rate their own health? Luy has answers to questions never asked before, and his findings could spark a rethink of the gender/health paradox.

Monks rule

You might see certain disadvantages to living in a monastery, but the health benefits are plain. For a start, it turns out that the longevity gender gap between women and men in cloisters is just one year – compared to six years for the rest of the population.

The big beneficiaries are men. For women, joining a convent appears to convey a small advantage over their lay counterparts - but men who enter a monastery live up to five years longer than other men.

Using the results of their survey and hard data on life expectancy from the excellent cloister records, Luy and his team calculated healthy life years for nuns and monks. They found that when it comes to less severe chronic diseases, male and female members of religious orders have more than their share: they spend a larger proportion of their lives with chronic health impairments.

But for serious diseases linked to premature death they do much better than their non-cloistered counterparts. Significantly, while monks live longer than other men, they also suffer more non-life-threatening chronic disease. Their health stories are not unlike those of an average woman – living longer than most men but in worse health.

It’s the lifestyle that counts

The translation of these insights to the gender differences in the general population confirmed Luy’s hypotheses. Just as he suspected, the idea that ‘women are sicker’ really depends on how health is defined. If you look only at life-threatening diseases, it is men who are worst hit. And yes, women accumulate more chronic conditions but this is because they have longer lives.

The Rule of St. Benedict, written about 530, was one of the founding documents of the (healthy) monastic lifestyle, prescribing a regular routine of manual labour, group prayer and readings, community spirit and obedience. Well, nothing’s perfect.

“We found that this disadvantage of women – whether in a convent or not – is in fact mostly a direct consequence of their advantage in longevity,” says Luy. “It reduces to a minimum when mortality differences between women and men are controlled for.”

Whether it is work-related stress, diet or something else that is killing non-monastic men is the next great question to answer. Or perhaps the low-meat diet and humble obedience prescribed by St Benedict’s Rule will become this year’s big lifestyle trend. Of course, though his study was of Christian religious, there is no reason to think the story would be different for monks and nuns of other faiths around the world; peace and quiet helps generally. For now, Luy draws an optimistic conclusion to his latest findings:

“The most important lesson we can learn from the nuns and monks study is that most of our longevity and health can be influenced by our own lifestyles, not just our gender.”

Can a booster-shot stop Alzheimer’s?

Weizmann Institute of Science, Israel
 

New approach recruits immune system to repair brain cells

Here’s a disturbing fact: Every 3.2 seconds, someone, somewhere in the world, develops dementia. Here’s another: It costs the world about $818 billion, or 1.09 per cent of global GDP – and that burden will grow rapidly.

Clearly, dementia is among the biggest challenges facing an ageing population. Yet, despite our pouring billions of euros into research over several decades, there has been no breakthrough. The search for an Alzheimer’s cure has been a particular source of despair – 99.6 per cent of drug trials end in failure. The handful of drugs that do exist help ease some symptoms. But none can undo damage to the brain cells we need to make new memories and retrieve old ones.

Michal Schwartz at the Weizmann Institute of Science in Israel has long suspected that a new approach is needed. It starts with the biology: The brains of people with Alzheimer’s are clogged up with ‘plaques’ and ‘tangles’ caused by proteins. The build-up of these proteins begins in the hippocampus, causing memory problems and confusion.

The Human Brain

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New thinking

Her theory? That the immune system normally plays a central role in repairing age-related memory loss – and that mechanism is what’s broken with Alzheimer’s patients. “Ageing of the brain is not so much a reflection of chronological ageing, but ageing of the immune system,” she says.

By this hypothesis, instead of using drugs to target sticky proteins on the brain, we could use immune-boosting medicines to do the trick. (Bonus good news: immune-boosting drugs already exist and are used in cancer patients.)

To say this notion went against the conventional wisdom for decades would be an understatement. But a growing body of research now suggests she was on to something.

“The brain is protected by the blood-brain barrier which filters out larger cells,” explains Schwartz, an ERC grantee. “The dominant concept in science was that no immune cells could cross this barrier under any circumstances because they are too large.” But over the past 20 years, her team have made a series of discoveries that are bringing a new kind of Alzheimer’s treatment tantalisingly close.

Protecting the brain

Knowing that the immune system kicks into gear to help repair damaged kidneys, lungs and other organs, she reasoned that the brain must get at least some help when it needs it. After all, the body’s most precious organ must surely deserve all the protection it can get.

“If the brain is such an indispensable tissue it doesn’t make sense that it’s not able to be helped by the immune system,” she recalls. “We discovered, very much against the dogma of the time, that both macrophages and T-cells [two types of immune cell] help to repair injury to the central nervous system – which includes the brain.”

At first, Schwartz did not understand how exactly this worked; but she persevered. Then, 10 years ago, her team published a landmark paper showing that immune cells play an important role not only when the brain is injured but also in maintaining everyday brain health.

The paper revealed that if the immune system of otherwise healthy animals is compromised, the brain can go haywire: it produces fewer new brain cells and copes less well with stress.

One of the key areas affected is the hippocampus, the region of the brain where Alzheimer’s disease strikes first. When the immune system is suppressed, it reduces plasticity – the ability of the brain to change and adapt, essential to brain function and memory.

Solving the riddle

This still left Schwartz with a big question: how exactly is the immune system helping the brain if immune cells are not able to cross the blood-brain barrier?

Then she cracked it: the blood-brain barrier is not the only way to access the brain. There’s a back door where the blood supply meets the cerebrospinal fluid (CSF) that surrounds the spine and brain.

“This is where communication between the immune system and the brain takes place,” says Schwartz. “It’s a gateway for macrophages when the brain is injured or under stress.”

When the brain is injured, it sends a distress signal to allow the immune system to come to the rescue through the CSF. In ageing, this communication channel begins to shut down.

So, when dementia begins to appear in an older person’s hippocampus, the body is less able to fight back. Brain cells die, memories fade, confusion sets in.

New medicine

“We have now found the mechanism that suppresses this vital communication between the immune system and the brain,” says Schwartz. In mice, “we have shown that if we reverse this suppression we can rejuvenate brain function.”

 

Michal Schwartz explains how the immune system can break through the wall between body and mind. Speaking at the Falling Walls 2013 conference, in Berlin.

By using medicines known to boost the immune system, her team did something remarkable: they repaired damage done in Alzheimer’s disease and restored brain function. In mice with Alzheimer’s-related memory loss, stimulating an immune response led to the clearance of sticky proteins and subsequent improved cognitive response.

Of course, the study was performed in mice – and so the results in humans may be different. But by looking at the brains of people who died with dementia, it appears that humans and mice share the same systems reported by Schwartz.

She is optimistic about the chances of success. And, because the immune-boosting drug is already licensed and used in cancer patients, they have a huge head-start on the drug development process. It is safe for humans; they can now test it on Alzheimer’s patients.

“I am working as fast as possible and hope that in two to three years we’ll be in clinical trials,” she says. “We already know it’s safe. The beauty of the treatment is that it’s not directed to anything in the brain – it’s directed at your immunity system.”

The scientific community is supportive. Olle Lindvall and Zaal Kokaia, professors at Lund University in Sweden, say Schwartz’s contribution has changed their field: “In our view, Michal Schwartz has pioneered and continues to have a leading role in research which has led to a paradigm shift regarding the role of immune cells in the central nervous system.”

They say that Schwartz' work has helped to understand normal functioning of the brain and how it is repaired after stroke. “Her work has demonstrated, for example, that a dysfunctional immune system contributes to inadequate regeneration after injury, which has raised the possibility of novel therapeutic approaches.”

What about you?

Schwarz’s work could be big news for people with dementia. But what about younger people in the full of their health? What does this tell us about staving off dementia later in life?

“The lesson is to keep your immune system in the best shape possible,” she says. “Good nutrition and reduced stress are good for the immune system.” And, of course, exercise helps: Sports improve your brain via the immune system.”

Even your gut bacteria may play a role. These ‘good bacteria’ determine the kinds of metabolites circulating in the body which in turn affect the immune system.

“If you’re interested in prevention I would say reduce stress, stay active and eat well,” says Schwarz.


Coming soon on ERC=Science2: Stressed out? So were the Victorians.

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