For centuries the elixir of eternal life – a potion to eradicate ailments and grant immortality – is the holy grail of medicine.
Now, thanks to a super mouse who led a short but amazing life in an American laboratory, the prospect of developing revolutionary drugs to help us live longer and healthier gives scientists energy worldwide.
"The race is discovering drugs and other interventions that will extend the life of humans," says Dr. João Pedro de Magalhães, a microbiologist and associate professor at the Institute of Aging and Chronic Disease at the University of Liverpool.
But this is not just about living longer: it is about living more of our lives in good health, free from the diseases that we accept as an inevitable part of aging – such as heart disease, dementia and cancer.
Scientists are trying not only to discover how we can give ourselves more over the years, but also how we can live longer with better health (photo of the file)
"People have been living in history for longer than ever before," says another leading researcher in the field, João Passos, associate professor of physiology at the Department of Geriatric Medicine and Gerontology at the Mayo Clinic in the US.
"The problem is that we live longer, but with multiple age-related diseases."
What scientists have realized, he told Good Health, is that "the cause of most diseases we experience in old age" is cell aging.
"So if we can focus on the mechanisms, maybe we can cure not only one disease, but all the different diseases together," he says. "That's the goal."
While Mail is launching a month-long series on lifestyle changes to live longer, we are looking at what science is revealing today – from long-lived rats to new & # 39; panacea & # 39; based on cheap, existing drugs – and questions: can a preventive anti-aging pill, or combination of pills, be only a few years away from middle age?
And can such treatments help people who already have age-related conditions, such as osteoarthritis?
ANTI-AGING JAB FOR KNEES
Thanks to medical advances, the average life expectancy in the UK in 2016 was 80 years, compared to 57 a century ago.
Realizing the huge potential in the longevity market, entrepreneurs such as Jeff Bezos, the Amazon founder, the Google company and PayPal founder Peter Thiel are pouring billions of dollars into this field.
Calico, the scientific company founded by Google in 2013 to tackle aging, has turned to clues for a carving rodent that only occurs in parts of East Africa.
The mole rat lives for more than 30 years and does not appear to show any of the usual physical decline associated with aging, such as muscle loss or heart problems.
Thanks to medical advances, the average life expectancy in the UK in 2016 was 80 years, compared to 57 a century ago (photo of the file)
Scientists discovered that the likelihood of dying at the age of 25 is the same as when he is one year old – comparable to a person who is not more likely to die at 90-30 – although it is not yet clear why.
However, it is the American super mouse who has spurred a new branch of aging 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, release compounds in the body that accelerates aging.
Since the 1960s, scientists have known that as we grow older, we collect increasing numbers of these cells, but it was not clear whether they were just a product of aging or whether they caused it.
The breakthrough came when scientists genetically modified a mouse, usually with a short lifespan and plagued by a series of age-related conditions, by injecting it with a synthetic drug called AP20187, designed to combat senescent cells.
CHEAP DIABETES PILL CAN KEEP THE KEY
A promising development in the field of aging was discovered almost by accident.
In 2014, research led by Cardiff University wanted to unravel the puzzle of why people with type 2 diabetes treated with a class of drugs called sulfonylureas had more cardiovascular problems and even mortality than metformin, another common diabetes drug.
They looked at 78,000 people treated with metformin, 12,200 on sulfonylureas and 90,000 without diabetes who had not received either – and were surprised to find that diabetics on metformin lived 15 percent longer than non-diabetics. Metformin is thought to block DNA damage and inflammation – important mechanisms of aging. Subsequent experiments have shown that the drug is able to extend the lifespan and delay the aging process in mice and roundworms. Two major trials to investigate the anti-aging potential of the drug in humans are now underway in the US
& # 39; Metformin is a generic, cheap, safe drug & # 39 ;, says Nir Barzilai, professor of genetics at the Institute for Aging Research in New York. "If it can target and delay aging, its administration should generally be associated with fewer age-related diseases."
& # 39; Every time the mouse made an obsolete cell, it deleted it: the cell committed suicide, says Professor Janet Lord, director of the Institute of Inflammation and Aging at the University of Birmingham. "And surprisingly, the mouse developed fewer age-related diseases."
It is important that the scientists have demonstrated clear benefits, regardless of whether the drug was administered sooner or later.
"Everyone in the field became very enthusiastic, because that was the first demonstration that an underlying process of aging could be tackled," says Lynne Cox, associate professor of biochemistry at the University of Oxford, who is also researching senescent cells.
Since then, there have been a number of studies that confirm the importance of such cells in the aging process.
In February, research in the journal Aging Cell showed that old mice that had been pre-treated with Navitoclax, an experimental anticancer medicine that kills senescent cells, recovered much better from an induced heart attack, increasing the prospect of a new type of treatment for people heart disease.
Another study, published in the journal EMBO, showed that clearing senescent cells from the hearts of mice also reduced the symptoms of aging, such as enlargement and thickening of the walls of the heart muscles.
Sanity-based Unity Biotechnology, funded by Bezos and Thiel, is now taking the next step – looking for drugs that can eliminate senescent cells in humans.
It has already conducted the first human test with such a drug, aimed at addressing moderate to severe osteoarthritis of the knee.
In the phase one study, 78 patients were divided into two groups: one was given a dummy drug while the other was injected into 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 investigation had been a success; UBX0101 was "well tolerated" by the treated patients who, after a single injection, had experienced "improvement in various clinical outcomes, including pain and function." Results from a larger phase two study are expected next year.
If the results of phase two are also successful, a drug could be on the market within a few years to treat osteoarthritis. Meanwhile, the Mayo Clinic has used the same approach to relieve the effects of idiopathic pulmonary fibrosis (IPF) – a gripping and ultimately fatal disease that usually strikes in later life, where the lungs become scarred until breathing becomes impossible.
With a combination of two drugs that have already been shown to alleviate the effects of IPF in mice – dasatinib, used to treat leukemia, and quercetin, a chemical found in plants and some foods, including red wine, onions and apples – the first human trial of 14 patients showed that, after just one week, most patients & # 39; significant and clinically meaningful & # 39; showed improvements.
Patients increased the distance they could walk in six minutes from an average of 447 meters to 468, and shortened the time needed to get up and sit in a chair five times from 14.8 seconds to 12.6. Large-scale tests will follow.
IS THE ANSWER A PILL CUTTING CALORIES?
Other teams experiment with different approaches to defeat the aging process, including genes.
As part of his human lifespan research, Dr. Magalhães and his team at the University of Liverpool have determined and analyzed the genome of Greenland whale, which is the world's longest living mammal with a lifespan of up to 200 years, but suffers from few age-related diseases.
"There must be a genetic component for the life of the bow," he told Good Health. "It is clear that they do not have access to any form of health care – so there must be natural mechanisms that protect them against diseases."
Some researchers try to beat the aging process by looking at genes and the possibility that reducing calories can help people to live longer (file photo)
The team is now working on identifying & # 39; promising candidate genes & # 39; that can explain the lifespan and good health of the whale, with the ultimate goal of developing a class of drugs that mimics the effects of these genes.
Animal studies have also shown that a reduction in calorie intake that stops malnutrition slows down aging.
Exhaustive studies with different compounds have shown three that seem to mimic the effect of calorie restriction: rapamycin, an antibiotic used to prevent the rejection of transplanted organs; allantoin, a substance 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 of these three compounds has already prolonged the life of roundworms.
"In animals, we can already extend the healthy lifespan by up to 50 percent – and if we could do that in humans, that would be remarkable," says Dr. Magalhães.
Other groups focus on the decline of the human immune system, which is thought to play an important role in age-related diseases.
Last year, scientists from the Novartis Institutes for BioMedical Research in the US reported that two types of experimental anti-aging drugs have successfully rejuvenated the immune system of people over 65.
Professor Janet Lord said: & # 39; Old age does not have to be a time of illness, but we cannot sit back and wait for pills & # 39; (photo of the file)
All 264 volunteers received a seasonal flu vaccine, but half received six weeks of treatment with two drugs designed to block the effects of a group of proteins involved in the aging 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 volunteers the following year and improved overall antiviral immunity, according to a report in Science Translational Medicine magazine last year, which demonstrated their potential to improve immune function. improve and reduce infection rates in the elderly & # 39; – a big step toward a longer, healthier life.
In the meantime, resTORbio – a Boston-based biopharmaceutical company developing drugs to tackle aging-related diseases – has launched two studies to test the effectiveness of a new drug, RTB101, for the treatment of respiratory tract infections in elderly patients.
It works by blocking an enzyme in the body, called TORC1, which is known to contribute to the deterioration of various organ systems as people age, and affects the immune system, brain and heart function.
SO HOW LONG PEOPLE LIVE FOR?
& # 39; Theoretically, there is no reason why an organism should not live forever & # 39 ;, says Dr. Magalhães.
"But for all animals, including mice, Greenland whales and us, the lifespan comes down to a matter of evolutionary biology.
"We are not designed for a long life, but for reproduction. Once you have reproduced, evolution no longer cares about you. We do not age because there is a reason for it; we age because there is no reason not to.
"Most of the ongoing work is designed to circumvent that lack of reason."
Associate professor Cox of the University of Oxford is careful about what can really be achieved when it comes to adding years to life.
"What is feasible in terms of sustainability is overhyped," she says. "What we are really talking about is increasing the" health span "- the number of years that people spend in good health."
According to Dr. Alison Giles, director for healthy aging at the Center For Aging Better, while research into increasing life expectancy is welcome, "it should not distract us from initiatives that can now improve the quality of later life."
"More people spend more of their lives in poor health, especially in less prosperous parts of the country, than in previous decades," she told Good Health.
"Stronger action is needed to help people smoke less and consume alcohol and to reduce the sugar and salt content of food."
Professor Janet Lord agrees: "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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