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?
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.)
Martin Prince is Professor of Epidemiological Psychiatry and co-Director of the Centre for Global Mental Health at King’s College London. He trained in Psychiatry at the Maudsley Hospital and in Epidemiology at the London School of Hygiene and Tropical Medicine.
His work is oriented to the salience of mental and neurological disorders to health and social policy in low and middle income countries (LMIC), with a focus on ageing, dementia and other chronic disease. He has coordinated, since 1998 the 10/66 Dementia Research Group, a network of researchers, mainly from LMIC working together to promote more good research into dementia in those regions. The group has published 140 papers covering dementia prevalence, incidence, aetiology and impact and contributed to knowledge of public health aspects of ageing and chronic disease in LMIC.
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.”
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.
Marc Luy is Head of the research group “Health and Longevity” at the Vienna Institute of Demography of the Austrian Academy of Sciences and Director of the German-Austrian “Cloister Study”. Previously, he was Junior-Professor for Demography and its Applications at the University of Rostock. Before becoming Junior-Professor, he was Doctoral Student and Research Scientist at the University of Rostock, the Max Planck Institute for Demographic Research in Rostock and the Federal Institute for Population Research in Wiesbaden, Germany. The main aim of his research is to disentangle the complex causation of healthy ageing through the study of differentials in health, mortality and longevity.
‘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.
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.
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.
“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.”
Michal Schwartz, Ph.D. is a world-renowned scientist in the field of neuroimmunology. She holds the positions of Professor of Neuroimmunology in the Department of Neurobiology at the Weizmann Institute of Science. She founded Proneuron, a biotech start-up, and served as one of its scientific advisors. She is a member of numerous professional committees and serves on the scientific advisory boards for global health organizations. Professor Schwartz has received many awards throughout her career, including an honorary doctorate from Ben-Gurion University of the Negev and the European Research Council (ERC) Award in 2008. She is a frequent lecturer and presenter and has published extensively. Professor Schwartz received her Ph.D. in chemical immunology and B.Sc. in chemistry, both from the Weizmann Institute.
Check this website to know more about her research: http://www.weizmann.ac.il/neurobiology/labs/schwartz/
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
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.
“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.
Tim Nawrot studied environmental health sciences at Maastricht University and Vermont Medical School, US. In 2005, he obtained his Ph.D. degree in medical sciences from the University of Leuven, Belgium. Nawrot currently works as an associate professor of environmental epidemiology at Hasselt University and part time (20%) at Leuven University. His research focus on health effects of environmental pollutants on ageing including effects in early life.
He has published over 100 scientific research papers including top medical journals as Lancet and British Medical Journal. He served as advisor on national and international panels in the field of environmental health including the World Health Organization and Canadian Health Administration. In 2008 and 2012, he was laureate of Belgian Academies of Medicine for his work on biological ageing and environmental epidemiology, respectively. In 2013, he was awarded a prestigious starting grant from the European Research Council (ERC).
Your mother’s diet and the air she breathed changes your risk of heart disease and cancer
How do you know when you’ve getting old? A few grey hairs, laughter lines, making noise when you pick something up from the floor?
Every time a cell divides, the telomere gets a little shorter. The length of your telomeres is a guide to the age of your cells.
Well, people with shorter telomeres live shorter lives. Worse, they are at higher risk of cardiovascular disease, cancer and Alzheimer’s disease.
Telomeres appears to act as a buffer against inflammation and oxidative stress which can trigger a cascade of age-related decline.
But we don’t all start life with cells of equal telomere length. Some babies have ‘older’ cells than others – a fact that follows them through life.
You’re only as old as you feel? Maybe.
You’re only as young as the length of your telomeres? Certainly.
Most research on ageing is done on older people. But we know that how we live helps to determine whether – and when – age-related illness strikes. Exercise, diet, stress and smoking can influence long-term health.
In fact, the closer scientists look, the more important our early days appear to be. Some say our first 1,000 days – including the 280 days we spend in the womb – set the tone for the decades that follow.
Tim Nawrot, professor of environmental epidemiology at Hasselt University, Belgium, runs an ERC-backed project looking at how factors such as air pollution and mothers’ lifestyles influence the lifespan of babies.
“Ageing is always studied in adults and the elderly,” he says. “What if the ageing process might start before birth?” he says. “And if so, what are the determinants in utero that make some children develop and age better than others?”
To do this, Nawrot’s team recruited more than 1,000 mothers and their infants at birth. They collected tissue from the placenta and blood from the umbilical cord, did a full health check on mother and child, and found out all they could about their living conditions – including income and diet.
One of the most important biological markers in the blood and in cells from the placenta are telomeres, the protective caps of DNA at the end of your chromosomes. “There’s a strong correlation between ageing and telomere length,” explains Nawrot. Short telomeres equal short life.
So, using telomeres as a sign of cellular ageing, he was able to draw some intriguing conclusions. The most eye-catching finding was big news around the world. As The Telegraph, a London newspaper not known for subtlety, headlined it: ‘Obese mothers shortening the lives of children by up to 17 years’
What your BMI says about your health
Nawrot compared the pre-pregnancy Body Mass Index (BMI) of women to the length of their new-born babies’ telomeres. His startling finding was that children born to obese women had telomeres so much shorter than children born to women of a healthy weight that they were likely to live between 12 and 17 years less, most likely with several chronic conditions.
All of that from measuring telomeres? “Having shorter telomeres at birth is not a problem in itself,” he explains. “But longer telomeres mean you can better withstand other stresses the cells will face later in life. Telomeres act like a kind of protective buffer.”
What's my BMI?
Nawrot says the finding should not be used as a stick to beat people struggling with their weight. Instead, it should make women stop and think, and prompt health authorities to invest in improving diets in the interests of preventing ill-health down the line.
“Around 30 per cent of women of reproductive age are at an unhealthy weight,” he says. “If you know that this influences the next generation’s risk of dying prematurely, it might motivate you to change.”
Every breath you take
Your mother’s health is not the only factor influencing how long you will live. Far from it. Gender and socioeconomic status are also associated with longevity.
A major area of interest for Nawrot is the role of air pollution. His study found that tiny dust particles (especially particulate matter with a diameter of less than 2.5 microns) is roughly as bad for us as being born to an obese mother or growing up in relative poverty. The trouble with these particles – produced by diesel engines, heavy industry, agriculture and shipping emissions – is their size. Not only do they affect the lungs of those who breathe them, but they are small enough to cross the blood-brain barrier and can get into every organ of the body where they cause damaging oxidative stress.
Nawrots’ research is far from over. In fact, the babies born at the beginning of the study are now six years old and were followed up between the ages of four and six to see how they were developing.
“We screened their cardiovascular health, bone density, nutrition, cognitive development and reaction times, along with other lifestyles factors,” he explains. His team is currently crunching the numbers to see whether factors like obesity and pollution have already hampered the well-being of children before they have even started school.
This group could be followed up throughout their lives to answer longer-term questions about the relationship between genes, telomeres, food, pollution, income and health. The big question will be to what extent some of the disadvantages we are born with can be reversed by making healthy choices later in life. For instance, says Nawrot: “If air pollution causes reduced telomere length in newborns, there should be a response. Shouldn’t we write environmental rules to protect the weakest and most vulnerable?”
Mikko Myrskylä is Executive Director of the Max Planck Institute for Demographic Research (MPIDR) and Professor of Social Statistics at the University of Helsinki. He joined the MPIDR from the London School of Economics where he served as Professor of Demography, and where he continues to work as Research Professor and lead a research group funded by the European Research Council. Professor Myrskylä holds a PhD in Demography from the University of Pennsylvania, and a PhD in Statistics from the University of Helsinki. His work focuses on population health, analysis of contemporary fertility trends, and demographic forecasting.
Research shows children born later may be taller and smarter, and their parents are happier- but there are many confounding factors.
Believe it or not, scientists don’t know everything. For instance, should you postpone having children until you’re older – for the sake of your, and their, health? It’s a tricky question to untangle, but researchers are trying.
Global fertility rates
The conventional wisdom says children born to older parents are less healthy than those with younger parents. Postponed parenthood, in the popular press, has been linked with everything from birth defects to autism.
As if that were not grim enough, many worry that as Europeans start their families later than ever, they tend to have fewer children – meaning there will be too few young people in the workforce in the decades to come. Globally, the fertility rate fell from 4.5 to 2.5 per couple between 1970 and 2014. In Europe, this is down to 1.6 – below the replacement rate of 2.1.
But Mikko Myrskylä, of the Max Planck Institute for Demographic Health in Rostock, Germany, doesn’t buy all this doom and gloom: he’s not sure the connection between parental age and children’s health is quite so clear cut.
While other researchers have found an association between ill-health and being born to older parents, the hard evidence that one actually causes the other is thin.
“My research leads me to believe that concerns about the health impact of postponing parenthood are based on outdated data,” he says. “We have been looking at new datasets and innovative statistical methods to get a much less biased view.”
For example, some earlier research compared health outcomes of people born to young or old parents, but failed to control for social class, education and parental income. To overcome some of these confounding factors, Myrskylä’s ERC-funded project compared the health of siblings born to the same parents, covering birth cohorts from the 1930s to the 1970s.
He found that those children born when the parents were older, and therefore also at a later date, lived longer. One reason was rather obvious: lifespans generally increased over that period as society got (mostly) more prosperous. “The children born later lived longer because almost everyone born in the 1950s was living longer than those born in the 1930s,” Myrskylä explains.
But these kids were also fitter and smarter. “In addition, children born later to older parents were taller, had higher IQs and better educational outcomes than those born earlier when their parents were younger,” he says.
In addition to benefiting from the broader trend towards living longer, a number of additional factors could explain the result. For a start, people in their early 20s might be less well prepared to have children: they are less mature, have fewer financial resources and are less likely to have reached a high level of education.
Whether this pattern would be replicated when future researchers compare children born in 2017 to those born in 2027 is impossible to say. “That’s a question for forecasters but we know that health and life expectancy have been improving and we see no signs of any limits,” Myrskylä says. “Even in countries where people live longest we are still seeing lengthening in lifespans thanks to improvements in how we treat cardiovascular disease.”
Older, happier parents
But forget the kids for a moment: what about the parents’ well-being? “In general, it has been said that having children decreases parents’ happiness,” says Myrskylä. “We have shown that this is true for very young parents where the effect can be long-lasting. In more mature parents, the overall impact of having children is positive, perhaps because they are readier to handle all the challenges that come with parenting.”
The Population Pyramid
This pyramid highlights the average percentage of different age groups globally. To view country and year specific information, please visit PopulationPyramid.net.
The economic impact of delaying parenthood might also be more positive than commonly presumed. Fertility rates decline when people start their families later, leading many to worry that Europe could one day have more retirees than workers as the population pyramid becomes top-heavy.
“There is a tendency to postpone having children but this trend may not continue,” Myrskylä says. “Many of those who choose to wait will eventually have children, leading the fertility rate to partially recover. In the meantime, they take the time to finish their education and get a foothold in their careers. Then when children arrive they are well resourced to handle it.”
So, that settles it. Everyone should shelve their baby-making plans until they are richer, more resilient and ready to have smarter, healthier kids?
“The results should not be taken as a prescription; everyone must decide for themselves,” says Myrskylä. “We must acknowledge that postponing having children increases the likelihood of being involuntarily childless. This is a cost and should be kept in mind.”
He says there is huge variation in the data: plenty of children born to young parents do very well and there is no shortage of people born to older parents who are not super-fit intellectuals.
“What we have shown is that in addition to the well-acknowledged negative effects of postponing childbearing, there are also important positive effects that are often larger than the negative ones,” Myrskylä explains. “And it is clear that more should be done to support parents who have children early in life, especially in the first few years.”