Is this proof science has found the key to beat ageing? As the Mail launches a vital anti-ageing series, the cutting edge research that could help us all live better for longer
- Genetically modified mouse in U.S. was injecting with drug called AP20187
- When made senescent cells, it deleted it and had fewer age-related illnesses
- Similar drug has already been used in human trial to tackle osteoarthritis of knee
- Reduction in calorie intake also found to slow ageing in animal experiments
- Scientists said not about increasing longevity but having bigger ‘health span’
For centuries, the elixir of eternal life — a magic potion to eradicate ills and grant immortality — has been the Holy Grail of medicine.
Now, thanks to a super-mouse that lived a short, but astonishing, life in a U.S. lab, the prospect of developing revolutionary drugs to help us live longer, healthier lives is energising scientists worldwide.
‘The race is on to discover drugs and other interventions that will increase human longevity,’ says Dr João Pedro de Magalhães, a microbiologist and senior lecturer at the University of Liverpool Institute of Ageing and Chronic Disease.
But this isn’t just about living longer: it’s about living more of our lives in good health, free from the diseases we accept as an inevitable part of ageing — such as heart disease, dementia and cancer.
Scientists are trying to discover not only how to give us all more years, but how to live longer with better health (file picture)
‘Human beings are already living longer than at any other time in history,’ says another lead researcher in the field, João Passos, an associate professor of physiology in the Division of Geriatric Medicine and Gerontology at the Mayo Clinic in the U.S.
‘The problem is that we are living longer, but with multiple age-related diseases.’
What scientists have come to realise, he told Good Health, is that ‘the driver of most of the diseases that we experience in old age’ is the ageing of the cells.
‘So, if we can target the mechanisms, we may be able to not only cure one disease, but all the different diseases together,’ he says. ‘That’s the goal.’
As the Mail launches a month-long series on lifestyle changes for living well for longer, today we look at what the science is revealing — from long-lived rats, to new ‘miracle’ drugs based on cheap, existing medicines — and ask: could a preventative anti-ageing pill, or combination of pills, taken from middle-age onwards be just a few years away?
And could such treatments help people who already have age-related conditions, such as osteoarthritis?
ANTI-AGEING JAB FOR KNEES
Thanks to medical advances, the average life expectancy in the UK in 2016 was 80 years, compared with 57 a century ago.
Realising the enormous potential in the longevity market, entrepreneurs including Jeff Bezos, the founder of Amazon, the company Google, and PayPal founder Peter Thiel are pouring billions of dollars into this field.
Calico, the scientific company founded by Google in 2013 to tackle ageing, has turned for clues to a burrowing rodent found only in parts of East Africa.
The mole rat lives for more than 30 years and appears to suffer none of the usual physical deterioration associated with ageing, such as muscle loss or heart problems.
Thanks to medical advances, the average life expectancy in the UK in 2016 was 80 years, compared with 57 a century ago (file picture)
Scientists discovered that its odds of dying aged 25 are the same as when it’s aged one — equivalent to a human being no more likely to die at 90 than 30 — although it’s not yet clear why.
However, it is the U.S. super-mouse that has spurred a new branch of ageing research.
The mouse was the star of breakthrough research, published in the journal Nature in 2011 by scientists from the Mayo Foundation for Medical Education and Research in Rochester, Minnesota, which focused on senescent cells — cells that stop dividing, then accumulate, releasing compounds in the body that accelerate ageing.
Since the Sixties, scientists have known that, as we age, we accumulate ever-greater numbers of these cells, but it wasn’t clear if they were just a product of ageing or whether they caused it.
The breakthrough came when scientists genetically modified a mouse, typically with a short lifespan and plagued with a range of age-related conditions, by injecting it with a synthetic drug called AP20187, designed to counter senescent cells.
CHEAP DIABETES PILL MAY HOLD THE KEY
A promising development in the anti-ageing field was discovered almost by accident.
In 2014, research led by Cardiff University set out to unravel the puzzle of why people with type 2 diabetes being treated with a class of drug called sulphonylureas suffered more cardiovascular problems and even deaths than those on metformin, another common diabetes drug.
They looked at 78,000 people treated with metformin, 12,200 on sulphonylureas and 90,000 without diabetes who’d received neither — and were surprised to discover that diabetics on metformin lived 15 per cent longer than the non-diabetics. It is thought that metformin blocks DNA damage and inflammation — key mechanisms of ageing. Subsequent experiments have shown that the drug is capable of increasing lifespan and delaying the ageing process in mice and roundworms. Two large trials to investigate the anti-ageing potential of the drug in humans are now under way in the U.S.
‘Metformin is a generic, cheap, safe drug,’ says Nir Barzilai, a professor in genetics at the Institute for Aging Research in New York. ‘If it can target and delay ageing, its administration should be associated with fewer age-related diseases in general.’
‘Every time the mouse made a senescent cell, it deleted it: the cell killed itself,’ says Professor Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham. ‘And, amazingly, the mouse developed fewer age-related diseases.’
Importantly, the scientists demonstrated clear benefits whether the drug was given in early or in late life.
‘Everybody in the field got very excited, because that was the first demonstration that there was an underlying process of ageing that could be tackled,’ says Lynne Cox, an associate professor in biochemistry at Oxford University, who is also researching senescent cells.
Since then, there have been a number of studies confirming the importance of such cells in the ageing process.
In February, research in the journal Aging Cell showed that old mice pre-treated with Navitoclax, an experimental anti-cancer drug that kills senescent cells, recovered much better from an induced heart attack, raising the prospect of a new type of treatment for people with heart conditions.
Another study, published in the journal EMBO, demonstrated that clearing out senescent cells from the hearts of mice also reduced symptoms of ageing, such as enlargement and thickening of the walls of the heart muscles.
San Francisco-based Unity Biotechnology, funded by Bezos and Thiel, is now embarking on the next step — searching for drugs that can eliminate senescent cells in humans.
It has already carried out the first human trial of one such drug, aimed at tackling moderate-to-severe osteoarthritis of the knee.
In the phase one trial, 78 patients were divided into two groups: one was given a dummy drug, while the other was injected in the knee with a drug codenamed UBX0101, which interferes with two proteins in the body, leading to the elimination of senescent cells.
In June, the company announced that the study had been a success; UBX0101 had been ‘well-tolerated’ by the treated patients, who, after a single injection, had experienced ‘improvement in several clinical outcomes, including pain and function’. Results of a bigger, phase two trial are expected next year.
If the phase two results are also successful, a drug could be on the market for treating osteoarthritis within a few years. Meanwhile, the Mayo Clinic has been using this same approach to alleviate the effects of idiopathic pulmonary fibrosis (IPF) — a harrowing and ultimately fatal disease that usually strikes in later life, in which the lungs become increasingly scarred, until breathing becomes impossible.
Using a combination of two drugs that have already been shown to alleviate the effects of IPF in mice — dasatinib, used to treat leukaemia, and quercetin, a chemical found in plants and some food, including red wine, onions and apples — the first human trial of 14 patients found that, after just one week, most of the patients showed ‘significant and clinically meaningful’ improvements.
Patients increased the distance they could walk in six minutes from an average of 447 metres to 468, and reduced the time it took to stand up and sit down five times in a chair from 14.8 seconds to 12.6. Large-scale trials will follow.
IS THE ANSWER A PILL THAT CUTS CALORIES?
Other teams are experimenting with different approaches to beating the ageing process, including genes.
As part of his research into human longevity, Dr Magalhães and his team at the University of Liverpool have sequenced and analysed the genome of the bowhead whale, which, with a lifespan of up to 200 years, may be the world’s longest-living mammal, yet suffers from few age-related diseases.
‘There has to be a genetic component to the longevity of the bowhead,’ he told Good Health. ‘Obviously, they don’t have access to any kind of healthcare — so there must be natural mechanisms protecting them against disease.’
Some researchers are trying to beat the ageing process by looking at genes and the possibility that cutting calories could help people live longer (file picture)
The team is now working on identifying ‘promising candidate genes’ that might explain the whale’s longevity and good health, with the ultimate goal of developing a class of drugs that mimics the effects of these genes.
A reduction in calorie intake that stops short of malnutrition has also been found to slow ageing in experiments on animals.
Exhaustive studies with different compounds have revealed three that appear to mimic the effect of caloric restriction: rapamycin, an antibiotic used to prevent the rejection of transplanted organs; allantoin, a compound found in plants and the urine of some mammals, used in everything from cosmetics to toothpaste; and trichostatin A, an antifungal antibiotic.
Treatment with one or other of these three compounds has already extended the lifespan of roundworms.
‘In animals, we can already extend healthy lifespan by up to 50 per cent — and if we could do that in humans, that would already be remarkable,’ says Dr Magalhães.
Other groups are focusing on the deterioration of the human immune system, which is thought to play a major part in age-related disease.
Last year, scientists at the Novartis Institutes for BioMedical Research in the U.S. reported that two types of experimental anti-ageing drugs successfully rejuvenated the immune systems of people aged over 65.
Professor Janet Lord said: ‘Old age doesn’t have to be a time of illness, but we can’t sit back and wait for pills’ (file picture)
All 264 volunteers were given a seasonal influenza vaccine, but half received it after first undergoing six weeks of treatment with two drugs designed to block the effects of a group of proteins involved in the ageing process — Certican, an antibiotic used to prevent organ rejection, and the cancer drug Dactolisib.
The drugs reduced the incidence of all infections — including flu — experienced by the volunteers over the following year and improved overall antiviral immunity, according to a report in the journal Science Translational Medicine last year, demonstrating their potential to ‘enhance immune function and decrease infection rates in the elderly’ — a big step towards longer, healthier lives.
Meanwhile, resTORbio — a Boston ‘biopharmaceutical’ firm developing medicines to target ageing-related diseases — has launched two trials to test the effectiveness of a new drug known as RTB101, to treat respiratory infections in elderly patients.
It works by blocking an enzyme in the body called TORC1, known to contribute to the decline of several organ systems as people age, affecting immune, brain and heart function.
SO HOW LONG COULD HUMANS LIVE FOR?
‘Theoretically, there’s no reason why any organism shouldn’t live for ever,’ says Dr Magalhães.
‘But, for all animals, including mice, bowhead whales and us, longevity comes down to an issue of evolutionary biology.
‘We are not designed for long life, but for reproduction. Once you have reproduced, evolution doesn’t care about you any more. We don’t age because there’s a reason for it; we age because there’s no reason for us not to.
‘Most of the work now under way is designed to bypass that lack of reason.’
Associate Professor Cox, of Oxford University, is cautious about what can really be achieved in terms of adding years to lifespan.
‘What is achievable in terms of longevity is being over-hyped,’ she says. ‘What we are really talking about is increasing “health span” — the number of years people spend in good health.’
According to Dr Alison Giles, director for healthy ageing at the Centre For Ageing Better, while research into increasing life expectancy is welcome, ‘it shouldn’t distract us from initiatives that could improve the quality of later life right now’.
‘More people are spending more of their lives in poor health, especially in less well-off parts of the country, than in previous decades,’ she told Good Health.
‘Bolder action is needed to help people cut back on smoking and alcohol and to reduce the sugar and salt content of food.’
Professor Janet Lord concurs: ‘Old age doesn’t have to be a time of illness, but we can’t sit back and wait for pills.’
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