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Scientists reverse some age effects in mice

Researchers artificially age rodents by suppressing a gene that helps repair telomeres, then rejuvenate them by turning back on the genetic switch. But the work is far from any use on humans.

December 04, 2010|By Amina Khan, Los Angeles Times
  • Using lab mice, scientists have shown that it is possible to reverse some effects of aging in mammals.
Using lab mice, scientists have shown that it is possible to reverse some… (Natacha Pisarenko / Associated…)

Have scientists finally discovered the genetic fountain of youth? Hardly. But by creating a genetic switch that allows them to artificially age — and rejuvenate — lab mice, scientists have shown that it is possible to reverse some effects of aging in mammals.

"It indicates there's a point of return if you remove the underlying cause of the aging," said Dr. Ronald DePinho, the molecular biologist at the Dana-Farber Cancer Institute at Harvard Medical School who led the study, published online this week in the journal Nature.

Scientists know that some of the signs of aging in humans are associated with telomeres, repetitive strands of DNA that protect the ends of chromosomes. (Chromosomes are the large bundles of DNA that contain our genetic blueprint.)

Telomeres "are like the caps on your shoelaces — they help maintain the package of your chromosomes," DePinho said.

As cells divide and replicate, these chromosome protectors get worn down and frayed over time. And with age, as telomeres shorten, signs of age-related degeneration — from graying hair to infertility to organ failure — emerge.

To figure out whether this process could be reversed, the scientists first engineered mice that aged artificially fast. In these rodents, the team had suppressed the gene that makes telomerase, an enzyme partly responsible for the repair of telomeres.

With prematurely shortened telomeres, the mice's coats grayed, their spleens atrophied and their brains and testes shrunk. Their skin was plagued by dermatitis and their sense of smell dulled. In short, they showed many signs of aging. At a normally youthful 6 months, they already looked 2 years old, DePinho said — equivalent to a human octogenarian.

The scientists then administered a drug that switched the suppressed telomerase gene back on. Soon enough, the mice regained the sheen in their coats, sensitivity in their noses and the sperm in their testes. The signs of age seemed to slough off them.

"The real pie-in-the-sky in the future is we learn how to control expression of this gene specifically and reawaken it transiently so the telomeres can be repaired," DePinho said.

"This work is really a tour de force," said Steven Artandi, a cancer biologist at the Stanford School of Medicine who was not involved in the experiment. He added that it would be interesting to see if telomerase could induce similar effects in naturally aged mice. But, he noted, the work on mice is far from being applicable to humans.

Aging, in any case, is a complicated process caused by many poorly understood factors, including problems with the cell's mitochondria, damage done over time by free radicals, and more.

Even if applied to humans, the gene could not be switched on permanently, but would have to be toggled on and off intermittently, Artandi added: "Telomerase is a tricky thing … it needs to be approached with caution," he said.

Immortal cancer cells, he pointed out, have telomerase to thank.

amina.khan@latimes.com

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