Organism Lives 10 Times as Long After Genetic Tinkering

Organism Lives 10 Times as Long After Genetic Tinkering

Dave Mosher / LiveScience Staff Writer
Mon Jan 14, 9:15 AM ET

Scientists have extended the lifespan of yeast, microbes responsible
for creating bread and beer, by 10-fold. That’s twice the previous
record for life extension in an organism.

The breakthrough could ultimately inform efforts to extend human lives.

Instead of one week, the yeast lived for about 10 weeks through genetic tinkering and a low-calorie diet.

"We’ve reprogrammed the healthy life of an organism," said Valter
Longo, a biologist at the University of Southern California in Los
Angeles who led the life-prolonging experiments.

Longo and his colleagues detail their findings in two upcoming
studies; one in the Jan. 25 issue of the journal PLoS Genetics and
another in the Jan. 14 issue of the Journal of Cell Biology.

Genetic soldiers

DNA, short for deoxyribonucleic acid, is the body’s set of blueprints and instructions, carried by genes.

"Evolution designed our genes, our army, to be ready for growth and
reproduction," Longo told LiveScience. Problem is, pooling the body’s
efforts into growing makes room for genetic errors that lead to
age-related disease. "We can use our energy to grow and reproduce, or
protect ourselves."

Longo and his team previously found two genes — RAS2 and SCH9 —
related to growth and development of cancer that are similar in humans
and yeast. They are so alike, in fact, that Longo said, "you can put
the human gene in yeast and it works."

The scientists disabled the genes in the yeast but also put the
organism on a low-calorie diet. Caloric restriction has prolonged the
lifespan of yeast, worms, and mice in other experiments, and is thought
to work by scaring the body into maintaining its genetic goods instead
of growing.

Combining both age-fighting approaches, Longo said, led to a dramatically long lease on life.

"We expected a small boost in longevity, but not a 10-fold increase," he said. "It’s remarkable."

Longo thinks the genes act like generals of the genetic army,
ordering the troops to protect the body’s DNA under caloric stress
instead of fighting for growth.

“I would say 10-fold is pretty significant,” said Anna McCormick,
chief of the genetics and cell biology branch at the National Institute
on Aging in Bethesda, Md, of Longo’s findings.

Hope for humans?

To find out how the age-defying treatment works in humans, Longo and
his group are now studying Ecuadorians who have similar mutations in
age-controlling genes used in the yeast.

“People with two copies of the mutations have very small stature and other defects,” he said.

Despite the problems, Longo said, the people likely benefit from their condition.

"So far, we have never seen cancer in people who have two copies of
the mutated genes," he said. “We are now identifying the relatives with
only one copy of the mutation, who are apparently normal. We hope that
they will show a reduced incidence of diseases and an extended life
span.”

Longo thinks life-extending drugs that have no major side effects
will not be easy to develop but should be possible in the future. He
explained that manipulating the genes leads to major growth defects
probably because they are inactive during childhood.

"What if we could achieve a balance by switching those genes off
when we want to?" he asked. "Twenty or thirty years from now, we might
have the ability to reduce the activity of [the genes]. In the long
run, I think that balance may not be too hard to achieve."

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