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Can we live forever as young old people?

We assume the ageing process to be a natural part of life that we must accept but many scientists now think we can act against it at the cellular level. Oliver Rowland spoke to French-Croatian biologist MIROSLAV RADMAN, author of a new book for the general public, Le Code de l’Immortalité, and to British ageing expert Dr Aubrey de Grey

23 January 2019
“If we invested like we do in the army we could live much longer but people are fatalistic “ says Prof Miroslav Radman
By Oliver Rowland

Miroslav Radman believes he has found the keys to slowing ageing. He describes biological ageing as “cultural vandalism” and says it is possible that in future people will be able to stay young and healthy indefinitely.

The eminent scientist told Connexion: “What we can do for a start is help people live up to the apparent maximum limit of around 120. Nearly everyone should be like Niemeyer, the Brazilian architect, who was creating splendid designs at 103. It doesn’t have to be the exception.

“If we have the knowledge to reinforce the weak links, or slow down the fire that burns us – the radicals – it’s legitimate to want to live in good health as long as possible and be productive for oneself and for society.”

Prof Radman, 74, a member of the French Academy of Sciences, added: “As long as one is not ill or disabled, you will never say – just because you’re out of work or something – you want to be killed. All that’s lacking is the science and technology. If we invested like we do in the army, we could live much longer, but people are fatalistic, they think there’s no point ima­gining a more beautiful and better life.”

Even so, he said he is “very confident” there can be effective therapies to slow down ageing in about 10 years time.

As for prospects of rejuvenating people who are already aged, he said: “I can’t see any scientific reason it’s not possible. We would just need to rejuvenate the body’s stem cells – that renew our intestine, the surface of the lungs, the nervous system’s glial cells, the neurones etc. In theory, there’s nothing against the possibility.”

Prof Radman has had an illustrious career with national research bodies Inserm and CNRS and as professor of cell-ular biology at the Université de Paris-Descartes. He was born in Split, Croatia, the son of a fisherman, and now spends much of his time at his privately-funded Mediterranean Institute for Life Sciences in his birth town, where he says he has more freedom to pursue his research.

He said: “People don’t realise that in the 19th century cancer was a luxury. It meant you hadn’t been killed by tuberculosis, paralysis, chickenpox... horrible infectious diseases.”

Hygiene, vaccinations and anti­biotics brought solutions for infectious diseases so people now die from degenerative diseases of old age, such as cancer and Alzheimer’s. However so far invest­ment that makes the moon lan­dings look like peanuts has brought “negligible success” in treating them, said Prof Radman.

He believes it is makes more sense to attack the root causes of ageing itself so as to intervene before such diseases develop.

He was inspired by the fact that some people are naturally highly resistant to diseases of old age and live to be 110 or more.

“There are 200 cancers and at least 100 degenerative diseases of the brain and muscles, cardio-vascular system etc. How can they fend off all of them? There had to be a common cause.

“If we wait for illnesses to develop and study the broken- down tissues, we find there are thousands of things that have changed. It’s too late, it’s like  waiting for an avalanche to smash everything, then see how many trees and homes were destroyed and in what way.”

Our bodies are built of cells, each of which has a nucleus with DNA molecules inside – carriers of genetic information – as well as other components such as proteins, large molecules that do most of the “work’” in a cell.

Prof Radman says he has identified oxidation of proteins and DNA as the main factor in ageing and found mechanisms in nature which protect against it and can be used for therapies.

He said there was little interest in studying the molecular basis of ageing in France before he started in 2003. This has now started to change and he claims some of the credit.

In 2009, he said Inserm had no anti-ageing projects. There are now 13 Inserm teams working on ageing in France, with support from industrialist Dassault.

Prof Radman said his first research was on a bacterium that can survive 5,000 times as much radiation as humans. “I wanted to understand how it has indestructible cells. Its DNA can be pulverised but it puts it back in the right order. How? It is because it protects its proteins, and they do every­thing in life; genes just allow the proteins to be renewed, because proteins are fragile – they oxidise, wear out, becoming dysfunctional.

“We’ve got to make new ones, and need instructions in genes. But I moved the focus in biology from genes to proteins, in bacteria and in tiny aquatic animals that are also ‘indestructible’.

“I found they invest a lot of energy in little anti-oxidant molecules that protect against oxidation: these ‘sacrificial mole­cules’ let themselves become oxidised before an oxygen radical hits the protein or DNA.”

He added: “Each protein is a different molecular machine with a different shape and size, and there are tens of thousands in our cells – that makes life.

“The whole of the proteins together interact like life’s software, allowing the synthesis of hundreds of thousands of small molecules of the metabolism that are needed for interactions and chemistry, and it all plays together like a huge orchestra.

“While it plays well, we are young and healthy and when it starts to play out of tune, the damage eventually reaches the conductor, which is the DNA, and one error provokes another and it becomes a vicious circle and the risk of dying and getting ill increases like an avalanche.”

Another expert, Aubrey de Grey (below), says the meta-bolism is so complex we should repair the damage that occurs in the cells as a side-effect of its processes rather than trying to prevent the cellular damage. Prof Radman disagrees.

“What’s better than stopping the DNA becoming oxidised in the first place?” he said. “We need to invest money and attention to use all possible means – it’s an ethical issue – so people don’t suffer, so they don’t get ill.”

Prof Radman was frustrated to find that panels that allocate research funding in France thought his ideas “too different”.

“They suffer from intellectual inbreeding – there’s not enough diversity. I had to change course and leave Paris and I got young researchers together in Split.

“I found money from British, US and Swiss venture capitalists and French industrialists.

“We’re independent and there are now two start-ups in Cam­bridge working on our projects. One is at pre-clinical stage [just before tests on people],” he said.

Another start-up company is working on a treatment that will soon be tested as a way of keeping people’s skin young.

“One of our approaches is sacrificial molecules. Another is based on a discovery called ‘chaperone molecules’.

“I’ve established that the chemistry of ageing is corrosion of the proteins, and secondly that accumulation of oxidised pro­teins increases with age.

“But we don’t all die at the same age of the same thing and this is because we have different weak links in our sequence of proteins. We could in theory predict from what illness a baby is going to die in 70 or 50 years.

“Antioxidants can help but we can also use chaperone molecules that protect the weak spots like a plaster. In the future there might be thousands of medicines for this.”

He added: “These processes happen to some extent in nature, otherwise we wouldn’t live long enough to reproduce – but now we want to live much longer in full health. We need to grow and acquire knowledge and so for the evolution of our culture we need ‘young old people’.

“Many French people think it’s immoral to want to live a long time, but they can’t imagine doing it in full health. Biological ageing is cultural vandalism.”

Another of his discoveries is cellular parabiosis. Para­biosis originally refers to linking the blood circulation systems of two animals, such as lab mice. He said researchers in California have had impressive results in rejuvenating older mice linked up to a younger one. “Illnesses regressed, memory loss and osteoporosis were reversed. But when separated the old mouse returned to the previous state.

“Cells do the same: there is a solidarity between cells. Dys­func­tional ones are helped by neighbours that don’t have the same faults. All age-related illnesses involve inflam­mation where com­mu­nication channels between the cells are cut off.”

Asked about his book’s bold use of “immortality”, Prof Rad­man said: “The title was my editor’s. I could have called it ‘Buy my book at all costs’.”

Anti-ageing will be the ‘next big thing’

British scientist Dr Aubrey de Grey (pictured, left) is just as passionate about anti-ageing and spoke in Monaco recently about progress in the field.

He believes the metabolic processes that lead to age-related damage are so complex that it is better to focus on repairing the cells with periodic use of therapies so damage never  leads to illnesses of old age such as heart disease, type 2 diabetes, Alzheimer’s or cancer.

“People die after dependence, decrepitude and misery and it’s terrible many people are ambivalent about doing something about it.”

Dr de Grey, formerly of Cambridge  Univer­sity and now chief science officer of the SENS Research Foundation in California (sens.org), which he co-founded, claims there are seven kinds of damage and it is possible to find therapies for all of them, which could be used to keep us physically young and healthy or rejuvenate older people. This is the focus of SRF, an independent research charity.

Classic medicine focuses on “trying to stop the diseases from becoming too severe, in spite of the damage which is idiotic”, he said. “The damage is still accumulating, so the therapies will get less and less effective as the person ages.

“It’s astonishing nobody had thought about ageing this way until I started saying these things 18 years ago, because it’s common sense.

“It’s the same as the way there are still classic cars over 100 years old that run as well as the day they were built due to preventative maintenance. People looked after them well – they got rid of the rust before the doors fell off.”

Dr de Grey said the field is “the next big thing”, with related investment funds setting up, including one in Paris, research now being done in many countries and start-ups using discoveries to develop therapies.

“France is playing a big role on the academic side – not much yet in the private sector, but that will happen soon. There is sufficient proof of concept so more money is flowing in and that will explode in a year or two. There is already a multibillion-dollar so-called anti-ageing industry built on products that basically don’t work. It will be amazing when we have ones that do.”

There should be clinical trials into treatments for all the kinds of damage within 10 years, he said, and the only thing slowing things down is sufficient research funding.

He said once available the new medicines will pay for themselves. “It’s very expensive to keep people alive in bad health. Plus healthy older people will be able to carry on contributing wealth to society in one way or another.

“It will be economic suicide for a country not to make the therapies available to those old enough to need them.” It can be compared to the benefits of free education, he said.

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