Source: Guardian
Date: 10 September 2005

Maverick who believes we can live for ever

Mark Honigsbaum

picture of Aubrey de Grey

In 1998 a scientist at the California Institute of Technology discovered a gene that could extend the life of fruit flies by 30%. He dubbed it the Methuselah gene after the Biblical prophet who lived to 969.

Now a self-taught gerontologist believes our mortality could one day be similarly extended.

At a conference at Queen's College, Cambridge, this week, Aubrey de Grey, a 41-year-old Cambridge computer scientist, told a research audience that there was no reason why people should not live to 1,000.

It sounds like science fiction, but for all that Dr de Grey has been dismissed as a crank, his papers continue to be published in peer-reviewed journals and scientists continue to flock to his meetings.

The editor of the MIT Technology Review has gone so far as to offer a $20,000 (£11,000) prize to any gerontologist who could put together a serious argument refuting his claims. So far there have been no takers.

According to Dr de Grey, such attacks are to be expected. "Traditionally, mainstream gerontologists have preferred to talk about compressing morbidity, but longevity is becoming impossible to avoid," he says.

Dr de Grey, whose day job includes investigating the fruit fly genome, says it is simply a matter of living long enough to take advantage of biotechnology therapies which promise to reverse the tissue damage that comes with age.

He calls his doctrine Strategies for Engineered Negligible Senescence, or Sens for short. He has identified seven deadly aspects of ageing, ranging from frayed DNA molecules to tangled proteins that interfere with neurons, sparking Parkinson's and Alzheimer's, to defects in mitochondria, the intracellular structures that power the cell and are vital to the control of free radicals involved in neuromuscular and other diseases.

Some of Dr de Grey's solutions, such as using stem cells to engineer new tissues, organs and nerve cells, are already in the works. But his most inventive contribution has been to propose radical solutions. One of these is a body-wide rubbish removal program that would clean up the junk that tends to accumulate inside cells by implanting in people genes from soil bacteria that have the ability to metabolise waste.

But to get to the stage where such interventions are feasible will require a huge research commitment. That is why, in a bid to convince the world that he is really on to something, Dr de Grey is offering a Methuselah Mouse prize of $160,000 to the first scientist who succeeds in extending the lifespan of an adult mouse from two to five - the equivalent, in human terms, of going from 80 to 150.

"At the moment the public and many gerontologists tend to put increased longevity in the same bracket as transponder beams - in other words, science fiction," admits Dr de Grey. "But once we meet the robust mouse test I predict scientists will fall in behind my theories and the public will insist politicians make these therapies available to everyone."

Millions are poured into research each year to counter the deleterious effects of ageing, with some scientists hoping that stem cells hold the key. However far-fetched Dr de Grey's theories, others at the conference were also offering solutions to the effects of ageing.

Michael West, the chief executive of the US biotech company Advanced Cell Technology and a world authority on human therapeutic cloning, presented a paper on how in the near future human somatic cells could be reprogrammed to treat neurodegenerative disorders such as Alzheimer's and Parkinson's.

And Ronald Kahn, professor of medicine at Harvard and the director of the Joslin diabetes research centre, described how his team were zeroing in on the secrets of the Klotho gene, yet another anti-ageing gene that has been shown to keep mice alive 30% longer than normal.

Others are more cautious of the grand sweep of Dr de Grey's claims.

"There's no doubt that Aubrey is an interesting guy but I don't buy a lot of his hyperbole," says David Finkelstein, the program director of the US National Institute of Ageing.

"Some of the extrapolations from animal experiments are frankly silly. Just because something works for a mouse that doesn't necessarily mean it's going to work for us."

Five bars to immortality

Signs of ageing and their solutions or cures, according to Aubrey de Grey

1 Cell depletion This happens in important tissues, including the heart and brain

Cure Treat primarily by introducing growth factors to stimulate cell division or by periodic transfusion of stem cells engineered to replace the types that have been lost

2 Unwanted cells In later years fat cells proliferate and replace muscle, sparking diabetes and heart disease

Cure Receptors on surface of such cells are susceptible to immune bodies that scientists will learn how to generate

3 Chromosome mutations Immortality of cancer cells is related to the behaviour of the telomere, the caplike structure found on the end of every chromosome, which decreases in length each time the cell divides

Cure Engineer cells so they no longer carry the gene for telomeres, thus stopping tumour from dividing. De Grey would also replace a person's stem cells every 10 years

4 Mitochondria mutations Mitochondria are the tiny machines that power the cell

Cure Copy genes from the mitochondrial DNA and put them into the DNA of the nucleus, where they will be safer from mutation-causing influences

5 Accumulation of 'junk' within the cell

As cells digest large molecules, the waste accumulates in intracellular structures called lysosomes. Atherosclerosis, hardening of the arteries, is biggest manifestation.

Cure De Grey proposes inserting genes from soil bacteria, which break down waste, into the lysosomes

* * *

Ending Aging (2007)
by Aubrey de Grey and Michael Rae
and further reading


Living Longer
Immortal Youth?
Longevity Genes
Reengineering the body?
Caloric restriction prolongs life
New treatments for aging brains
World's Oldest Supercentenarians
Does resveratrol enhance longevity?
Does caloric restriction significantly prolong life?