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Cellular spring cleaning may keep us youthful and healthy for longer

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The in-built process of maintaining the health of our cells by recycling dead or toxic material plays a key role in our health overall. Known as autophagy, researchers are now keen to know if boosting the natural process may hold off the debilitating diseases of old age.

By intervening in the processes that make our bodies and brains malfunction as we get older, can we delay the onset of age-related disorders, or even stop them developing entirely?

The mythical fountain of youth has been a popular legend for thousands of years. The question of whether we can drink from its waters has been nagging modern researchers working in the field of biological ageing (known as senescence) since 1889, when French doctor Charles-Édouard Brown-Séquard injected himself with extracts from animal testicles. Following this, he claimed his mental and physical condition improved.

Almost 150 years on, age-related disorders like Alzheimer’s and heart disease have reached epidemic levels in the Global North, and the quest for rejuvenation has lost none of its appeal.

Unsurprisingly, rising life expectancy is largely to blame for this surge in disease. People born in Europe today can expect to live until they are aged 81.3 – a good 35 years longer than those entering the world in the late 19th century – however, medics agree that quality of life in old age has not kept pace with longevity. Many of us spend our elderly years – sometimes decades – living with mental or physical conditions caused almost entirely by the ageing process.

Often there are no treatments for the conditions of old age, and the symptoms can be ‘highly debilitating – sometimes devastating,’ according to Professor Nektarios Tavernarakis, a bioscientist at the University of Crete in Greece who studies ageing, cell death and neurodegeneration.

‘Our aim needs to shift from staying alive for longer to achieving a better quality of life in old age,’ said Prof. Tavernarakis, who is also principle coordinator of the EU-funded MANNA project.

Cell detox

Prof. Tavernarakis and his colleagues are intent on understanding – and ultimately fixing – the cellular causes of biological decline. The benefits of extending a person’s healthy years will be felt by society at large. Poor health in old-age poses a huge and growing burden on our social and healthcare systems. Alzheimer’s disease alone affects more than 4.9 million people in Europe, and diseases and disorders of the nervous system and brain bring an annual cost of around €800 billion to Europe, according to 2010 figures.

The question is, how can scientists hope to solve the problem of physiological decline when there is such a smorgasbord of seemingly unrelated disorders vying for their attention? From cancers to diseases that affect the internal organs, circulatory system and nervous system, there are many conditions associated with ageing.

Essential housekeeping

Many are pinning their hopes on a biological process known as autophagy (meaning ‘self-eating’ in Greek). All cells use autophagy to rid themselves of toxic material (mostly unnecessary or damaged components). As we age, this essential housekeeping task is performed less efficiently leading to the buildup of errors and glitches that trigger disease-causing inflammation and ultimately necrotic cell death (known as necrosis).

There is growing evidence that faulty autophagy is a common denominator in many of the disorders linked to old age. Necrosis contributes to incidence of tumours, liver disease, stroke, heart disease, and age-associated neurodegenerative disorders such as Alzheimer’s and Parkinson’s.

Studies in this area are in their infancy, but a burgeoning body of research suggests that boosting autophagy can extend cell survival and improve our prospects of good health.

Looking to the future, Professor Linda Partridge, founding director of the Max Planck Institute for Biology of Ageing in Germany, said: ‘We see the prospect of developing a single pill that will target the biological pathways that also involve autophagy. The idea would be to have a polypill that prevents the underlying mechanisms involved in more than one ageing-related condition.’

‘If we could target those underlying processes of ageing, we might be able to slow down age-related degeneration and keep people healthier for longer. This would take us to a different place from where we are in now, where diseases are tackled one by one, as they arise.’

Prof. Partridge is the lead researcher of GeroProtect, an EU-funded project that sets out to find suitable drug candidate for such a ‘geroprotective’ polypill. ‘We’re not looking to increase lifespan, but to solve the problem of the ever-growing period of ill-health at the end of life,’ she said.

Prof. Tavernarakis’ MANNA is focused on unpacking the link between autophagy and age-related degeneration of the nervous system. Much of the group’s work is carried out on the worm Caenorhabditis elegans, which, perhaps surprisingly, has a nervous system that’s remarkably similar to that of humans.

During the first four years of this project, the team has uncovered some of the key genes and molecular players involved in nerve-cell necrosis. Their work confirms that the survival and long-term maintenance of neurons is dependent on a sub-type of autophagy called mitophagy.

Toxic build-up

In its prime, an organism uses mitophagy to eliminate old or toxic mitochondria (these are the organelles used by a cell to convert glucose – or simple sugar – into useful energy). But as age sets in and mitophagy slows down, faulty mitochondria start to accumulate in nerve cells. This build-up is toxic, triggering an inflammatory response that leads to cell damage and death. It’s this progressive loss of functional nerve cells that causes a neurodegenerative disease to emerge.

‘Through our work on both C. elegans and human brain tissue, we can confirm that mitophagy is downregulated in Alzheimer’s patients,’ said Prof. Tavernarakis. He added that efforts to decipher the precise mechanisms involved in mitophagic failure are still unfolding, but he is confident that complex genetic therapies will eventually be available to replace gene sequences that promote necrosis with ones that support healthy autophagy well into old age. Such therapies, however, are many years off.

Eat less, live longer

One known way to induce autophagy is through caloric restriction. In experiments spanning worms, flies, mice, chimps and humans, researchers have found that consuming less food, or restricting an organism’s feeding hours within a given day, activates autophagy.

In non-human species, dietary restriction has also been found to extend lifespan and reduce or delay the onset of age-related conditions. Depending on the species, the most promising results show lifespan extensions of between 50 – 300%. There is tantalising evidence that dietary restriction has positive impacts on the ageing of primates too, though the effects in humans remain controversial.

Why might it help to go hungry? Quite simply, when the diet of an organism is restricted, its cells become deprived of glucose and begin to consume their own redundant material to generate energy. In other words, to sustain themselves, cells are forced into a detoxifying state of autophagy.

Disease prevention

The problem with dietary restrictions is that generally people don’t like them, and any attempt to reduce food intake tends to be short-term in humans. So, when it comes to enhancing autophagy, pharmaceutical interventions are a far more realistic prospect (though Prof. Partridge stresses that over-activating autophagy can also be problematic, as this can lead to cells destroying their contents at unfavourably high rates).

A number of promising drug candidates have already been identified. Most notable are Urolithin A (produced by certain gut bacteria after they’ve been fed with ellagitannins, which are found in pomegranates, strawberries, raspberries and walnuts) and rapamycin (a natural antifungal produced by soil bacteria).

These two compounds are known to be involved in the upregulation of autophagy. In mice, worms and fruitflies, they have also been found to extend lifespan. Shortly, the geroprotective properties of these compounds will be put to the test in human clinical trials.

Prof. Partridge – who has been studying the underlying mechanisms that make rapamycin effective in boosting autophagy in animal models – is hopeful that the results of human trials will take her team closer to developing their game-changing polypill.

‘Eventually we may end up with a drug that is taken very much like people today take statins (for cholesterol) or pills to lower blood pressure,’ she said. ‘Medicines that are taken over a very long period of time to prevent ill-health long before disease has even occurred.’

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Why more heatwaves endanger our health and ability to work

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As the Earth warms, heatwaves are expected to occur more often, with sharper intensity and for longer periods. Rising temperatures adversely affect worker productivity and human health, but for policymakers to take substantive action for heat adaptation, and meet what researchers see as a life-saving Paris climate agreement, making an economic case is key.

BY NATALIE GROVER

As the Earth warms, heatwaves are expected to occur more often, with sharper intensity and for longer periods. Rising temperatures adversely affect worker productivity and human health, but for policymakers to take substantive action for heat adaptation, and meet what researchers see as a life-saving Paris climate agreement, making an economic case is key. This article first appeared in Horizon Magazine in August 2020.

It’s actually quite easy for us to point out the problem — we have increasing temperatures, increasing frequency of heatwaves…it affects our physical and cognitive performance,’ said Lars Nybo, a professor of integrative physiology from the University of Copenhagen, Denmark. He worked on a project called HEAT-SHIELD designed to examine the effects of heat exposure on worker productivity in industrial sectors that employ half of Europe’s workforce: manufacturing, construction, transportation, tourism, and agriculture. The project ran from January 2016 until December 2021.

Globally, 2021 was among the seven hottest on record, with Europe experiencing its hottest summer to date. In the Mediterranean region, an intense and prolonged heatwave in July and August lead to new temperature records and devastating wildfires, a poignant reminder that the achievement of the Paris climate agreement to keep global mean temperature increases well below 2°C is as important as ever.

Data from HEAT-SHIELD project suggest that exposure to external heat in combination with physical activity, which elevates the body’s production of heat, can result in physiological changes that can diminish occupational performance, via reduced working endurance, vision, motor coordination and concentration. This can lead to more mistakes as well as injuries.

‘Roughly 70% of all European workers, at some time during the working day, are not optimally hydrated,’ Prof. Nybo said. The solution to the problem, he added, is intuitive: drink water, replace electrolytes and reduce physical activity, but implementing these measures whilst maintaining productivity is where things get tricky. 

‘You could just say to the worker stay at home and drink cold margaritas in the shadow to prevent heat stress,’ he joked. ‘But that will not help productivity.’

Productivity

As coordinator of HEAT-SHIELD, Prof. Nybo and his team were tasked with not just assessing the extent of the problem — modelling the expected rise in temperature in Europe in the coming years and its impact on worker productivity ­— but also devising and implementing solutions that are location and vocation specific to adjust to the inevitable increases in temperature.

A construction worker wears a safety helmet, which impairs the body’s ability to purge heat, but the worker thinks this problem cannot be solved because it is intrinsic to their work, Prof. Nybo noted.

Surmounting challenges like this was one of the key objectives of the project — conceiving ways to weave in heat mitigation strategies alongside the practicalities of the job.

For instance, outdoor workers should be vigilant of weather patterns and plan work earlier in the day during periods of extreme heat, take a short break every hour and secure easy access to water. Similar remedies for workers in enclosed settings could mean a combination of air conditioning, working in shade and improving ventilation — keeping in mind the ecological footprint of such measures.

But on a macro level, for climate change policymakers to take concrete action here and now ­— the numbers are key, Prof. Nybo said.

In Europe, agricultural and construction workers for instance, lose some 15% of effective working time when the temperature goes beyond 30°C, which works out to almost one working day per week, he noted, citing HEAT-SHIELD analyses.

If you are a policymaker, he says, the numbers show that there’s an incentive to act now: if you mitigate the problem the cost will stabilise at a lower level in the long run than if you don’t.

Excessive heat

Diminished worker productivity and the downstream economic damage are prominent impacts of rising temperatures caused by climate change. But to get a full picture of the consequences, it’s necessary to understand what excessive heat does to the human body.

It can damage organs such as the heart and the lungs, exacerbate a range of diseases, and increase the risk of death.

Extreme heat can increase the occurrence of heart attacks and strokes in susceptible patients due to increased blood viscosity, and raise the risk of cardiovascular death in vulnerable patients. Hot, humid days can also trigger asthma symptoms and have been shown to increase airway resistance, while warmer climates tend to extend the pollen season.

Another side effect of rising temperatures is the association with air pollution — the largest environmental killer in Europe, causing roughly 500,000 premature deaths annually.

Observational data and modelling suggest that as it gets warmer, air pollution levels — particularly surface ozone gas (O3) and fine particulate matter (PM2.5) — increase in some populated regions, even when emissions of air pollutants have not risen, as well as create conditions favourable for forest fires.

Both extreme heat and air pollution raise the risk of cardiovascular and respiratory disease, which currently costs the European Union an estimated €600bn a year. If these environmental stressors continue to accumulate unabated, these costs could jump.

Projections

But the synergistic relationship between air pollutants and rising temperatures is not well understood and existing health-risk projections in Europe do not properly account for adaptive measures that can be taken to ameliorate associated health risks, according to Dr Kristin Aunan, a senior researcher at the Norway-based Center for International Climate Research.  

‘There’s quite a lot of literature on short-term impact — in terms of the day-to-day variation on the impact of heat stress on mortality — but when it comes to long-term impact, there is not a lot of information,’ she said.

As part of a project called EXHAUSTION that kicked off in 2019 and is due to run until May 2023, researchers including project coordinator Dr Aunan, are focused on quantifying the risks of cardiopulmonary disease in different temperatures.

The project is also working on identifying interventions to minimise the risks to health sparked by environmental stressors and demystifying the link between air pollution and temperature hikes.

Quantifying the cascading effect of cardiopulmonary diseases on the economy is key to affecting action on climate change, she suggests.

EXHAUSTION researchers, for instance, are devising a macro-economic model that tracks increased hospitalisation and mortality in different age groups to measure the impact on the broader economy in different European countries. ‘We also have a bottom-up model — where you put a price on every premature death or hospital admission and add up to estimate the economic cost.’

One of the main questions the researchers hope to answer is the magnitude of impact limiting temperature spikes to 1.5°C — the aim of the Paris climate agreement — will have on health. 

‘I have no answer to that today — but the reason why we’re doing this project…is that we think there are reasons to believe that being able to comply with a Paris agreement will save very many lives and reduce human suffering,’ Dr Aunan said.

‘When you discuss climate policy and discuss the costs of it — it’s very expensive to reduce emissions of greenhouse gases, etc. But you also need to consider the benefits and that’s what we are doing with this project — hoping that we can contribute to the other side of the coin.’

This article first appeared in Horizon Magazine in August 2020.

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Children at risk of new ‘unexplained acute hepatitis’ outbreak

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The world is currently facing a new outbreak of “unexplained acute hepatitis infections” affecting children, the World Health Organization (WHO) warned on Thursday, World Hepatitis Day.

The current uptick focuses attention on the thousands of acute viral hepatitis infections that occur every year among children, adolescents, and adults.

Treat hepatitis

WHO, together with scientists and policymakers in affected countries, are working to understand the cause of this infection that does not appear to belong to any of the known five types of hepatitis viruses: A, B, C, D, and E.

While the world has the guidance and tools to diagnose, treat, and prevent chronic viral hepatitis, these services are often out of reach for communities and are sometimes only available at centralized or specialized hospitals.

“To be most effective, hepatitis care must be delivered in communities through strong primary healthcare and integrated with other health services that address the full range of health needs,” WHO chief Tedros Adhanom Gebreyesus said in his message for World Hepatitis Day.

At risk

Although most acute infections cause mild disease and even go undetected, some can lead to complications and turn fatal.

In 2019 alone, complications of acute hepatitis A to E infections caused an estimated 78,000 deaths worldwide.

Global efforts prioritize the elimination of hepatitis B, C and D infections.

Unlike acute viral hepatitis, B, C and D cause chronic disease, which lasts for several decades, culminating in over one million deaths per year from cirrhosis and liver cancer. And they are responsible for over 95 per cent of hepatitis deaths.

Death every 30 seconds

“Every 30 seconds, someone dies from hepatitis-related diseases, including liver failure, cirrhosis and cancer,” said the WHO chief.

Moreover, some 80 per cent of people living with the disease are unable to access or afford care.

With the goal of eliminating hepatitis by 2030, the UN health agency has called on countries to reach four specific targets.

It aims to reduce new infections of hepatitis B and C by 90 per cent; reduce hepatitis-related deaths from liver cirrhosis and cancer by 65 per cent; ensure that at least 90 per cent of people with hepatitis B and C virus are diagnosed; and at least 80 per cent of those eligible, receive appropriate treatment.

Low coverage of testing and treatment is the most important gap to be addressed, in order to achieve the global elimination goals by 2030,” according to WHO.

Call to action

WHO is calling on all governments and partners to “scale up the use of effective tools” against the potentially deadly disease.

Tedros drew attention to a new WHO report that shows how Brazil, Egypt, Georgia, Mongolia, Rwanda, Thailand and the United Kingdom, are making progress towards the elimination of hepatitis B and C by applying the UN health agency’s tools and guidelines.

“With political commitment and investment, the elimination of viral hepatitis is within our reach,” he stated.

July spotlight

The day aims to raise awareness of viral hepatitis, which causes inflammation of the liver that leads to severe disease and liver cancer.

It also offers an opportunity to step up national and international efforts on the infection, encourage individuals, partners and the public to act, and highlights the need for a greater global response, as outlined in the WHO’s Global hepatitis report of 2017.

This year, WHO is highlighting the importance of bringing hepatitis care closer to primary health facilities and communities for better access treatment, no matter the type of hepatitis.

The 28 July date was chosen because it is the birthday of Nobel-prize winning scientist Baruch Blumberg, who discovered hepatitis B virus (HBV) and developed a diagnostic test and vaccine for the virus. 

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Tone as important as truth to counter vaccine fake news

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By ALEX WHITING

Lack of trust in health authorities, combined with the fear and uncertainty about the disease, created fertile ground for false rumours to spread about Covid-19 vaccines. Countering the rumours may be about attitude as well as facts.

False assertions about Covid-19 vaccines have had a deadly impact – they are one reason why some people delayed being inoculated until it was too late. Some still refuse to be vaccinated.

More than two years after the start of the pandemic, false rumours continue to circulate that the vaccines do not work, cause illness and death, have not been properly tested and even contain microchips or toxic metals.

Now a study raises hopes of deflecting such falsehoods in future by changing the tone of official health messaging and building people’s trust.

In many countries, public confidence in government, media, the pharmaceutical industry and health experts was already on the wane before the pandemic. And in some cases, it deteriorated further during the rollout of Covid vaccines.

This was partly because some national campaigns said the jabs would protect people from falling ill.

Friends over facts

‘There was a lot of overpromising around the vaccine without really knowing what would happen,’ said Prof Dimitra Dimitrakopoulou, research scientist and Marie Curie Global Fellow at the Massachusetts Institute of Technology and the University of Zurich.

‘Then people started getting sick, even though they were vaccinated. That created a lack of trust in the government issuing these policies, and in the scientific community.’

Prof Dimitrakopoulou studied public perceptions of Covid vaccines and obstacles to acceptance of reliable information as part of a project called FAKEOLOGY.

She found that, when people lose faith in institutional sources, they end up relying only on themselves, close friends and family.

‘They trust their instincts, they trust what resonates with them,’ Prof Dimitrakopoulou said. That means they will search the internet, social media and other sources until they find information that reinforces the beliefs they already hold.

‘We have lived with fake news and misinformation long enough to understand that it cannot be debunked with facts,’ she said. ‘People just raise these emotional blocks.’

For example, a story about a mother whose child fell sick after getting a Covid vaccination would likely be more influential than a message containing scientific facts.

Building trust

Prof Dimitrakopoulou surveyed 3 200 parents of children under 11 years old in the United States, and conducted focus groups with 54 of them, to discuss their views about Covid vaccines for kids.

Many parents felt confused by conflicting information about the shots and had a lot of questions about their effectiveness.

She gave the parents a selection of messages to assess. They were put off by the ones that were largely factual, rigid and prescriptive – the tone of many public health campaigns.

They were more persuaded by messages that addressed their concerns about the vaccines with empathy and compassion while acknowledging that they face a difficult decision.

‘We need to be ready to answer any questions they may have and be ready to have a conversation – without expecting the conversation to end with someone getting vaccinated,’ said Prof Dimitrakopoulou.

Those exchanges will ultimately help bolster public faith in health bodies and government institutions. ‘Covid is a great opportunity for us to start building this trust,’ she said.

While a lengthy process, building these bridges could enlighten people’s perceptions for the rest of their lives, she said.

Fake news filter

It is also important for journalists, researchers and the general public to be able to spot and filter out fake news.

Researchers on a project called SocialTruth have developed a tool to flag fake news content on the internet and social media.
 
The software, called a Digital Companion, can check the reliability of a piece of information. It analyses the text, images, source and author and, within two minutes, produces a credibility score – a rating of between one and five stars.

‘This is a computer-generated score that can give a red-flag warning if the content is very similar to other types of content that have been found to be false,’ said Dr Konstantinos Demestichas, researcher at the Institute of Communication and Computer Systems in Athens and coordinator of SocialTruth.

The Digital Companion uses computer algorithms that draw on a wide variety of verification services. These include non-governmental organisations, businesses and academic institutions – all with different interests, opinions and intentions.

Because of the diversity of verification-service providers, ‘We need to establish their trustworthiness by continuously evaluating their results,’ said Dr Demestichas.

To do this, the project uses blockchain to record all the scores and results produced by the verifiers. If the verifiers perform poorly, they lose their status – ensuring the Digital Companion can offer a quality assurance, he said.

Digital and human fact checkers

For now, the technology has been developed to scan health science and political content. In future, it could be developed for almost all areas.

Initially it will be for institutions that monitor fake news and disinformation, but the aim is to enable journalists and the general public to take advantage of the resource too.

The technology ‘could really make a difference in the daily use of the internet and social media,’ said Dr Demestichas.

Still, because it will never be able to spot all fake news, ‘We need journalists, fact checkers, and citizens to be well-trained to exercise their critical thinking,’ he said.

Manipulated feelings

The fight against misinformation is about more than protecting people’s health, important as that is. The well-being of democratic societies themselves is also at stake, said Dr Demestichas.

‘Fake news tries to manipulate our feelings and fears to get our “clicks” to read their content,’ he said.

Curbing it is critical ‘to defend our democracies and allow our societies to function better.’

The research in this article was funded by the EU. This article was originally published in Horizon, the EU Research and Innovation Magazine

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