Source: Northwestern University
Date: 14 September 2009

Could there be a cure for ageing?

By curing Alzheimer's, Parkinson's disease and cancer, some scientists say we could live forever.

By Danny Penman

An ageing face Photo: GETTY CREATIVE Cranks and crooks have been peddling immortality potions since before the dawn of history. All manner of bizarre antidotes to ageing have been tried, including the drinking of mercury salts and the eating of diced monkey testicles.

Immortality, it would seem, has long been inextricably entwined with lunacy. But that may be about to change. Earlier this month, 200 scientists descended on Queens' College Cambridge to discuss ways of radically extending human lifespan – and even achieving immortality. The Strategies for Engineered Negligible Senescence (SENS) conference, drew together researchers from disciplines as diverse as tissue engineering, artificial intelligence, law, demographics and politics.

"Most people fail to understand how fast medical science is advancing in this area," says the conference organiser Dr Aubrey de Grey, editor-in-chief of the journal Rejuvenation Research and co-founder of the SENS Foundation. "Conventional medical progress has ensured that a child born today can expect to live 120 to 150 years. I think it's possible for them to live far longer.

"If we make the right breakthroughs in the next 25 years, then there is a 50:50 chance that people alive today could live to be 1,000 years old."

This might seem fantastical but Dr de Grey is garnering a surprising amount of support.

"Aubrey de Grey is not crazy," says Professor Mark Pepys, a biomedical researcher at University College London and one of the conference speakers. "He's got serious hard-core scientists working for him that are doing great work on ageing."

The "normal" rate of medical progress ensures that life expectancy increases by about two years every decade. This ensures that for every hour that passes, you have gained 12 minutes of life expectancy. Accelerate the rate of progress, and you stand a chance of achieving "take-off"– the point at which life expectancy increases faster than the population ages.

The delegates attending the conference, inevitably dubbed "the immortalists", see ageing as primarily an engineering problem. They believe the human body can be coaxed into eternal life by replacing body parts as they wear out and by upgrading the body's biochemistry as problems emerge. They think that such procedures will become commonplace two or three decades from now.

The scientists are not looking for a single "magic bullet" to cure ageing but are instead battling the diseases of old age such as Alzheimer's, cancer and cardiovascular disorders. They believe that if you successfully treat or cure such diseases, then death will be postponed, perhaps indefinitely. Immortality will become a side-effect of medical progress.

Until the early Seventies, scientists believed that all living organisms had a pre-programmed maximum lifespan. Then Professor Tom Kirkwood of Newcastle University proposed the "disposable soma theory". This claims that we die because the genes that code for maintenance functions, such as DNA repair and antioxidant enzymes, progressively lose their vitality. This is because life is a balance between two competing forces; the need to reproduce and maintain the body long enough to do so. Put simply, our bodies only maintain themselves long enough to produce children.

Paradoxically, the disposable soma theory also opens up the possibility of immortality. If we could ramp up the body's maintenance processes – or artificially repair any damage by replacing body parts – then we could live much longer.

Dr de Grey has identified seven categories of damage that need to be tackled:

  • cancer;

  • mitochondrial mutations, that is mutations of structures inside cells that produce energy by converting glucose, which thereby disrupts energy supply;

  • cell loss, for example Parkinson's disease;

  • cell senescence leading to a weakened immune system;

  • extracellular crosslinks, which physically "stiffen" major organs leading to, for example, inflammation and arteriosclerosis;

  • the build-up of intracellular "junk" proteins, which physically interfere with cellular functioning such as brain signalling in the case of Alzheimer's; and

  • extracellular "junk" proteins resulting in amyloidosis, a harmful build-up of proteins around the major organs.

Progress in all seven areas is rapid. Alzheimer's, which results from the build-up of both intracellular and extracellular "junk" proteins is a prime example. These form plaques, known as amyloid, which interfere with the smooth running of the brain. The same problem appears to be the root cause of Type II diabetes and several other diseases.

Reversing the build-up of amyloid could result in curing a range of lethal conditions, as well as expanding lifespan. Two recent breakthroughs suggest that it could happen within a decade.

The monoclonal antibody Bapineuzumab, which encourages the body's immune sytem to recognise and break down amyloid deposits currently undergoing clinical trials, appears to reverse the build-up of amyloid plaques in the brain.

Professor Mark Pepys, a biomedical researcher at University College London, has also developed a highly promising treatment for a related disease known as amyloidosis – characterised by the build-up of amyloid in tissues and organs throughout the body. It may also be effective against Alzheimer's, too. His treatment works by coupling an antibody to a drug known as CPHPC. The antibody carries the drug to the amyloid plaques which then breaks them down.

Both treatments offer the hope of treating Alzheimer's. But even more importantly, both approaches offer the hope of reversing other diseases caused by the build-up of intracellular and extracellular aggregates such as Type II diabetes.

Last month, scientists in America announced they had found a way of eliminating inherited mitochondria diseases, muscular wasting diseases such as Leber's Hereditary Optic Atrophy, which is progressive visual impairment, after perfecting a technique for breeding monkeys with three parents. They did this by transferring the nucleus from an egg which had faulty mitochondria to an egg with healthy mitochondria that had been stripped of its nucleus. The resulting hybrid egg was then fertilised in the usual way. This procedure circumvents a major failing in animal reproduction, namely that mitochondria can only be inherited through the maternal line, so are far more vulnerable to genetic diseases.

Custom-building body parts – or even replacing whole limbs – may seem like the realm of science fiction but this may soon become reality.

Already scientists routinely produce skin and simple body parts, such as ears. Twelve years ago, the world was stunned by the picture of a human ear growing on the back of a mouse. Since then, the technique has advanced so fast that body parts are now routinely grown in vats rather than in animals. More than 300,000 people have now received such tissue-engineered body parts.

Professor Chris Mason, a biomedical researcher at King's College London, says that in decades to come, even custom-building body parts may seem quaint.

"The focus is now on regenerative medicine," says Professor Mason. "There are two main approaches. The 'simplest' involves injecting stem cells into the damaged area, such as the heart, and leaving them to repair the damage. The second way is more complex but may prove more fruitful. In this, you would take a medicine to mobilise the body's own stem cells and encourage them to migrate to the site of damage and repair it."

Professor Mason believes that in a few decades it may be possible to coax the body into growing its own body parts. He points to the US Defense Advanced Research Projects Agency's 40–year "salamander programme", which is working on ways to help soldiers to re-grow limbs lost in battle.

"Humans can naturally regenerate some parts of their body, such as the liver and tongue," says Professor Mason. "In principle, we should be able to re-grow other bits too, such as, arms and legs."

Amidst all of this optimism, some scientists are urging caution. Richard Faragher, chair of the British Society for Research on Ageing, worries that the claims made by Aubrey de Grey and the other "immortalists" is obscuring other areas of medicine that will benefit patients far more.

"Aubrey is effectively a science-fiction writer," says Dr Faragher. "There are many ways that public health can be improved through simple measures such as managing hip fractures more effectively. We should be focusing on these things rather than dreaming about immortality."
and further reading

PHA-4 gene
Living Forever?
Immortal Youth?
Longevity Genes
Yoda the Ancient
Caloric Restriction
Daf-2 and longevity
Reengineering the body?
Caloric Restriction: pitfalls
Stress, telomerase and aging
New treatments for aging brains
World's Oldest Supercentenarians
Can slight caloric restriction prolong life?
Caloric Restriction: humans vs nonhumans