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October 13, 2005

Science 2005: Examining how genes affect aging

Armed with whimsical line drawings of greybeard cartoon worms leaning on canes and with a gift for expressing complex ideas in simple terms, molecular biologist Cynthia Kenyon wrapped up the University’s annual science and technology showcase with a discussion of the effect of hormones on aging.

Kenyon, a biochemistry and biophysics professor at the University of California-San Francisco, presented “From Worms to Mammals: The Hormonal Regulation of the Life Span” as the keynote Mellon Lecture speaker Oct. 7.

She and others have linked age-related diseases to genetic mutations. Her work with worms has helped prompt a shift in the way scientists think about aging.

Through genetic manipulation, she was able to extend the life of the soil-dwelling worm caenorhabditis elegans to six times its natural lifespan, the equivalent of a human living 500 years.

“The challenge now is to determine the effects of her findings on the human condition,” said Arthur Levine, senior vice chancellor for Health Sciences and dean of the School of Medicine, in his introductory comments.

“Aging has been thought to be something that just happens in a passive, uncontrolled way,” Kenyon said. Just as one set of genes controls development, research increasingly is showing how genes control aging and lifespan as well.

“I thought since aging is such a fundamental, ubiquitous process, maybe it was subject to some kind of control,” she said.

Her 1993 research with a mutant form of C elegans with the lifespan of twice its normal counterparts found that mutations that damage the daf-2 gene also extend life.

“The normal function of the gene is to speed up the aging process,” she said, informally dubbing it the “grim reaper gene.” Those with damaged daf-2 not only lived longer, but the older worms were active and vigorous.

“It was not like they were in the nursing home and just hanging in there,” she said. “They just seemed to be aging more slowly.”

Other research found similar results in fruit flies and mice.

Scientists predict that genes could play the same role in human aging.

In humans, the ability of a person to live to be 100 has a very strong genetic component with longevity tending to run in families, she said.

The reproductive system also plays a role. Kenyon found that altering the daf-2 and removing the reproductive system in a worm increased its lifespan six-fold.

“This really makes you wonder just how far you can go,” she said.

Researchers also are exploring the link between aging and disease. “You’re 100 times more likely to get a tumor at 65 than 35,” she said.

“What exactly is it that makes you more likely to get these diseases when you’re elderly?”

The link apparently is more about biological age than chronological age.

Mice may get cancer at 1 year of age, while it may appear in dogs at age 10.

“Both are elderly at that point,” Kenyon said.

“Genes are a contributing factor, but they’re not the whole story,” she said.

Other researchers have found that the long-lived mutant worms also were resistant to environmental stress, prompting questions about the link between stress-resistance and longevity.

“The question is, could this little worm lead us to the fountain of youth?” she said.

—Kimberly K. Barlow

Filed under: Feature,Volume 38 Issue 4

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