Organism Lives 10 Times as Long After Genetic Tinkering (and CR)

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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 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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