Who wants to live for ever? A scientific breakthrough could mean humans
live for hundreds of years*

By tweaking our DNA, we could soon survive for hundreds of years – if we
want to. Steve Connor reports on a breakthrough that has the science
world divided

26 January 2008

A genetically engineered organism that lives 10 times longer than normal
has been created by scientists in California. It is the greatest
extension of longevity yet achieved by researchers investigating the
scientific nature of ageing.

If this work could ever be translated into humans, it would mean that we
might one day see people living for 800 years. But is this ever going to
be a realistic possibility?

Valter Longo is one of the small but influential group of specialists in
this area who believes that an 800-year life isn't just possible, it is
inevitable. It was his work at the University of Southern California
that led to the creation of a strain of yeast fungus that can live for
10 weeks or more, instead of dying at its usual maximum age of just one
week.

By deleting two genes within the yeast's genome and putting it on a
calorie-restricted diet, Longo was able to extend tenfold the lifespan
of the same common yeast cells used by bakers and brewers. The study is
published later this week in the journal Public Library of Science Genetics.

There is, of course, a huge difference between yeast cells and people,
but that hasn't stopped Longo and his colleagues suggesting that the
work is directly relevant to human ageing and longevity. "We're setting
the foundation for reprogramming healthy life. If we can find out how
the longevity mechanism works, it can be applied to every cell in every
living organism," Longo says.

"We're very, very far from making a person live to 800 years of age. I
don't think it's going to be very complicated to get to 120 and remain
healthy, but at a certain point I think it will be possible to get
people to live to 800. I don't think there is an upper limit to the life
of any organism."

For most gerontologists – people who study the science of ageing – such
statements are almost heretical. There is a general view in this field
that there is a maximum human lifespan of not more than about 125 years.
Jeanne Calment, the oldest documented person, died at the age of 122
years and 164 days. According to the orthodox view of ageing, she was
one of the few lucky enough to have reached that maximum, upper limit of
human lifespan.

The attitude of most mainstream gerontologists towards the idea that
people may one day live for many centuries – or even 1,000 years, as one
scientific maverick has suggested – is best summed up by Robin Holliday,
a distinguished British gerontologist, in his recent book Aging: The
Paradox of Life. "How is it possible to make these claims?" Holliday
asks. "The first requirement is to ignore the huge literature on ageing
research... The second is to ignore the enormous amount of information
that has been obtained by the study of human age-associated disease; in
other words, to ignore the many well-documented textbooks on human
pathology. The third is to propose that in the future, stem-cell
technology, and other technologies, will allow vulnerable parts of the
body to be replaced and/or repaired. The new 'bionic' man will therefore
escape from ageing," Holliday says.

Like many experts on the science of ageing, Holliday is deeply sceptical
about the idea that the ageing process can somehow be circumvented,
allowing people to extend their lives by decades or even centuries. "The
whole [anti-ageing] movement not only becomes science fiction; it is
also breathtakingly arrogant," Holliday says. An immense hinterland of
biomedicine suggests that death at a maximum age of about 125 is
inevitable, he says.

But that is precisely what Valter Longo is suggesting with his work on
the yeast that can live longer than 10 weeks. "We got a tenfold
life-span extension, which is, I think, the longest that has ever been
achieved in any organism," he says.

By knocking out two genes, known as RAS2 and SCH9, which promote ageing
in yeast and cancer in humans, and putting the microbes on a diet low in
calories, Longo achieved the sort of life extension that should in
theory be impossible. As Anna McCormick, head of genetics and cell
biology at the US National Institute on Aging, remarked: "I would say
tenfold is pretty significant."

Calorie restriction is now a well-established route to extending the
lives of many organisms, from yeast and nematode worms to fruit flies
and mice. But the jury is still out on whether calorie restriction can
extend the life of humans, although a diet rich in calories certainly
increases the risk of obesity, diabetes and other life-shortening
conditions.

Biologists believe that restricting calories causes many animals to flip
into a state normally reserved for near starvation. Instead of spending
their precious energy reserves on reproduction, they shut down
everything but their basic body maintenance, in preparation for better
times ahead when breeding would stand a better chance of success.

This idea fits in with the more general view that animals tend to follow
one of two life strategies – either one of high fecundity and short
lifespan, or one of long lifespan and low reproductive capacity.

Mice, for example, divert much of their limited resources to high
reproduction, having several litters of young a year, but they have a
short life of just a couple of years. But bats, which are roughly the
same size as mice, have just one or at most two offspring a year, and
can live for 30 years or more.

Why one species of animal lives longer than another of comparable size,
and why some animals appear to age faster and die younger, have been the
subject of extensive scrutiny for decades. As bats and mice show, it is
possible for genes to extend lifespan – so the question is: why do they
not do it more often, or even all the time? And the logical extension of
this question is: why do we age at all? Why don't we live for ever?

One of the most convincing answers to this is known as the disposable
soma theory. In short, the idea is that genes can extend an organism's
lifespan, but only as a trade-off between the costs and benefits of
doing so. It is possible to keep on mending the machinery of the body as
it suffers daily wear and tear, but there comes a point when it is no
longer worthwhile and the costs become too expensive, much like the
point when fixing an increasingly decrepit car gets too much. At this
point the body, or "soma", becomes disposable. By then, though, from the
gene's point of view, it won't matter – as long as it has managed to
"escape" this broken-down body and replicated itself inside the younger,
fitter bodies of the next generation.

Longo says that the disposable soma theory, invented by Professor Tom
Kirkwood of Newcastle University in the late 1970s, is one of the
strongest ideas around to explain the nature of ageing.

However, Longo has another theory that is causing a second group of
scientists to tear their hair out. He believes that ageing may not
simply be a side-effect of the wear and tear of life, but is also a
genetically programmed condition designed to rid the population of aged
individuals to make way for younger ones.

It is an alluring idea, albeit one thought to have been discredited by
the evolutionary biologists George Williams and John Maynard Smith 40
years ago. It is a common assumption among non-scientists that ageing
and death occur in order to make way for the next generation, but this
suggests that ageing is a genetic programme honed by natural selection.
It also assumes that it is an altruistic act brought about for the
benefit of the future population.

Evolutionary biologists know that such an idea is based on "group
selection" and that mathematically this cannot occur because it will
always be undermined by more selfish mutants. Organisms carrying the
altruistic genes for premature ageing and death would, for instance, be
susceptible to selfish-gene cheats that decide to exploit the situation
to their own, and their offspring's, advantage. They could simply live a
bit longer than their peer group and so make sure they are the ones that
exploit the available resources left behind by their prematurely dead peers.

But Longo is convinced that his experiments on manipulating the genes of
yeast show that ageing is not a mere side-effect of life, but a
deliberate, genetically programmed process honed by natural selection.
"Basically, it is the first demonstration, to our knowledge, that ageing
is programmed and altruistic," Longo says. "The organisms we have
studied die long before they have to in order to provide nutrients for
'mutants' generated within their own population. Thus, billions of
organisms die early so that a few better-adapted individuals can grow."

This raises the possibility that the same process happens in humans, and
that, as a result, many people are dying earlier than they need to.
"Programmed human ageing is just a possibility. We don't know whether
it's true yet or not. But if ageing is programmed in yeast, and the
[metabolic] pathway is very similar, then isn't it possible that humans
also die earlier than they have to?"

Valter Longo says that no one has so far proved him to be wrong on his
programmed-death idea. But this may be one heresy too far for the rest
of science.

 From the Archives: Jeremy Laurance reports from Japan, the country with
more centenarians than any other (see independent.co.uk/science)

Enduring tales: the world's oldest people

Jeanne Calment

Jeanne Calment's mother, father and brother lived to 86, 93 and 97
respectively. But nobody has eclipsed Jeanne herself, who died in 1997
aged 122 years and 164 days. Born in 1875, she met Vincent van Gogh when
she was 14, and attended the 1885 funeral of Victor Hugo.

Shigechiyo Izumi

As well as holding the title of the oldest man to have lived, Izumi,
from the Japanese island of Tokunoshima, holds the record for the
longest career. A farmer, he worked from childhood until the age of 105,
in a career that spanned 98 years. In spite of a weakness for sho-chu (a
barley whisky) and taking up smoking at 70, he lived to 120. He died in
1986.

Edna Parker

Indiana-born Parker, 114, has outlived all her children, but her family
includes 13 great-great-grandchildren. Now recognised as the world's
oldest living person, she grew up on a farm. Still walking, she hobbles
around her nursing home, where she enjoys reading and reciting poetry.

Charlotte Hughes

Hughes, a retired schoolteacher, is the oldest documented person in the
UK. She married her husband, Noel, at the age of 63. He died aged 105,
but Hughes went on to reach 115, dying in 1993.

Florrie Baldwin

Baldwin, born in 1896, lives in a Leeds nursing home. Britain's oldest
living woman says she remembers meeting Queen Victoria on a royal visit,
and reading about the end of the Boer War. She has outlived her husband,
Clifford, by 35 years.

Henry Allingham

Allingham has found fame in recent years as the oldest veteran of the
First World War, one of only a handful still alive. Born in 1896, south
London-born Allingham, 111, is also Europe's oldest living man, and in
the world is second only to Japan's Tomoji Tanabe.