Do you want to live to be 800? This man says that you can

March 10, 2006

A biogerontologist claims ageing can be reversed. Not all agree, finds Becky McCall

I t comes as something of a surprise when Aubrey de Grey - a man who promotes a scientific theory that is dependent on some of the most cutting-edge medical technology - asks for help in operating a mobile phone. But then de Grey, a self-taught biogerontologist at Cambridge University, does not live in the here and now; he is preoccupied with a world 1,000 years away.

According to de Grey, this futuristic world could, theoretically, be populated with people who are today already aged 60. The concept of ageing will be obsolete, and if his strategy to delay death works, we will be suspended in a state of eternal youth, with cancer, heart disease and other 21st-century diseases confined to medical history.

De Grey is a theoretician and is the first to admit that it is unlikely anyone will ever catch him in a laboratory. He has a first degree and PhD in computer engineering and last studied biology at O level, but he crammed extensively under the tuition of his wife, 19 years his senior and a professor of genetics also at Cambridge. He argues that his unconventional background is probably central to his revolutionary thinking.

"There's a long and distinguished history of scientists moving into a new field unencumbered by the conventional wisdom. There are some shining examples - just look at Francis Crick for one, who began as a physicist and had never practised experimental biology."

De Grey's moment of enlightenment arrived at 4am in a hotel room in Los Angeles. His ideas distil current medical research into a seven-stranded plan known as the Strategy for Engineered Negligible Senescence, or Sens.

In essence, the application of Sens will reverse ageing by eliminating known causes of senescence: cell loss; nuclear and mitochondrial mutation; old cells that fail to self-destruct; improper bonding between protein and sugars leading to reduced elasticity; junk inside and outside of cells that eventually lead to death.

But even if we cure these seven causes of ageing and death, basic biology predicts that new ones are likely to emerge to replace them. In defiance of this obstacle to his theory, de Grey has developed another pivotal tenet to support it: escape velocity. This is where the figures come in. After all, age is just a number. Escape velocity refers to the ability to cure causes of ageing at a rate that exceeds the development of new mechanisms of ageing. To clarify this concept, de Grey compares the human body to a vintage car. "With effort, we can fix nearly everything that can go wrong with these machines and maintain them almost indefinitely. Once you have managed to maintain a car that was built to last 15 years for 50 years, then it doesn't get any harder to keep it in good working order for 100 years."

But the human body is far more complex than a car. "I am asking how we can achieve the same effect, presuming that we knew the mechanisms by which we could fix an ageing body. If we could fix half of each of the seven signs of ageing, then we could, in effect, take 60-year-olds and rejuvenate them back to, say, 40ish. Then, because there are still parts of the car that aren't fixed yet, they continue to age but more slowly. In 25 years, they will be back to where they started but by then there will be other more advanced means of fixing things - 25 to 30 years is a long time in the development of technology so we will be able to fix the same people again but with new, more effective mechanisms," he explains.

Such radical theories are not without their opponents, and de Grey is no stranger to resistance from the scientific community. "I am attempting to bring about a change in thinking that is bigger than anything that the field has undergone before. What is happening is reminiscent of Gandhi's famous description of campaigns that change people's thinking: 'First they ignore you, then they laugh at you, then they oppose you and then they say they were with you all along.' I'm at the third stage," he says.

Last November, 28 gerontologists expressed their opposition to his ideas in the European Molecular Biology Organisation Reports . They claim de Grey is doing the field of biogerontology serious harm by promoting a research agenda that in their view is utterly unsupported by scientific knowledge.

Shortly after, de Grey took on Huber Warner, the lead author of the EMBO Reports article in a debate at the Gerontological Society of America. By the end, Warner had invited de Grey to write up an account of his talk for publication in the EMBO , one of the most conservative biogerontology journals available.

Determined to have his theory stand up to scrutiny, de Grey has set up the Sens Challenge. In return for a prize of $20,000 (£11,500), he invites molecular biologists to submit an intellectually serious argument as to why Sens is wrong and unworthy of learned debate. So far, nobody has come forward.

Critics of de Grey's theory also argue that it is short-termist: if we all live to the ripe old age of several hundred years, where will we all go and how will our already plundered Earth cope? It is unlikely that humans will lose the impulse to procreate even if they do live for centuries, but will our reproductive life expectancies keep up, and what of relationships - will we really say until death do us part for 800 years?

De Grey has answers to some, if not all, of these questions, and his outlook is ever optimistic. "As for reproduction, the chances are we will have fixed that. We'll be able to restore fertility to a youthful state by sticking in new ovaries or repopulating them with eggs. This is probably the simplest way." He admits that the problem posed by overpopulation could be more difficult to solve.

"Politicians should worry because if I'm right on the science, then the world will be a very different place - and I mean in ten years when these therapies become anticipated. People will make different life decisions."

With minimal chance of death from disease or other causes, the concept of risk will change, which will lead to practical problems, such as how you convince people to become fire fighters.

Stephen Minger, a stem-cell scientist at King's College London, says that we know very little about upper age limits and that de Grey's theories might not be as far-fetched as they initially sound. "He's not a bench scientist in the conventional sense but he does understand the issues more than people think. We know that it's possible to take animals with a predictable age course and by various means extend their life by 50 per cent. In essence, what he's saying is that as long as you continue to stay alive then you can reap the benefits - given that you don't get hit by a car or whatever."

Others in the field of gerontology support the introduction of new ideas to stimulate debate about longevity but feel that his crusade for a massive research programme is doing the field an unwarranted disservice.

Jim Edwardson, of the Institute for Ageing and Health at Newcastle General Hospital, says: "Most of us in the field of ageing are trying to extend 'healthspan' and not lifespan. The pressing challenge is to understand why cells and tissues age, and why these aged cells and tissues become more vulnerable to disease. Despite billions of pounds spent on research by the global pharmaceutical industry and medical science, we still don't understand why age is the biggest single risk factor for dementia, nor do we have an effective treatment."

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