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January 4, 2011

Aging Gene

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Anti-aging Gene (03.26.04) - Most of us think aging is inevitable, but one scientist has committed her career to proving us wrong.
Most of us think aging is inevitable, but one scientist has committed her career to proving us wrong.

Why We Age (09.29.05) - Some mice that age three times faster than normal are revealing to scientists why we grow old.

Living to 100 (11.01.05) - A long life is said to be a blessing, and a study of people who live to 100 shows it is — most of them enjoy amazingly good health. For some it's genetic.

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Aging and Genetics

The Genes That Control Aging

National Institute of Aging

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image: Makoto Kuro-o
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There may be no need to search for the fountain of youth. A new animal study shows it may be inside of us, in the form of a gene that prolongs the lifespan of mice. This ScienCentral News video has more.

Age Busting Gene

Methuselah is said to have hit 969, Jared 962 and Noah over 500. We're not talking career home runs here, but biblical-era birthdays. Since no one's matched these records to date, most of us have more modest numbers in mind when we think about living a long, healthy life.
"Eighty-five… that's a good number to me," says Gregoire Boisrond, a 33-year-old technician in New York City.

Floridian Liz Whiteside, a mere toddler on the longevity scale at 24, has higher aspirations: "Heck, I'd live to 120 if I could do it."

We all hope to have healthy golden years.
image: The Osteoporosis Foundation
As scientists slowly pick apart the biological mechanisms that cause us to age, the future could see more of us winding up closer to Liz's ideal. Fresh evidence from an animal study shows how a gene called "klotho" — named for the Greek goddess who spins the thread of life — acts like a natural anti-aging hormone in genetically engineered mice.

"The extension of lifespan of the klotho mice was about 20 to 30 percent on average compared to [normal] mice," says Makoto Kuro-o, the University of Texas Southwestern Medical Center researcher who led the study. "So it's a very significant extension and [klotho mice] are probably among the most long-lived animals or long-lived mice so far reported."

The longevity these special rodents enjoy may be the result of the klotho gene preventing what scientists call "oxidative stress," or damage in cells, tissues, or organs caused by free radicals, environmental pollutants, or even bacterial, fungal or viral infections. Over time, DNA changes in response to this chemical onslaught, cells die, and aging sets in.

Kevin Rosenblatt, one of the paper's co-authors, says we can't avoid that kind of damage. "Oxidative stress can be brought on by just living."

Large mouse with over-expressed Klotho gene
So the researchers decided to take a closer look at aging by tracking oxidative damage in two groups of mice, those genetically engineered to make more of the klotho gene's product — a protein that Kuro-o says acts like a hormone that "circulates in the blood and sends messages all over the tissues" — and a group of normal mice. After injecting both with the herbicide paraquat, the team measured oxidative damage by looking at the DNA the animals shed in the blood stream and excrete in urine.

The researchers found the klotho mice fared better. "The normal mice had much higher levels of oxidative damage," says Rosenblatt. "That indicated that the [klotho] mice had higher levels of enzymes that repair the damaged DNA versus the [normal mice]."

Have Kuro-o and his group stumbled upon the chemical fountain of youth? After all, people have the klotho gene too. The answer is, not likely. For starters, the klotho mice have a few biological peculiarities we'd want to do without: they have fewer offspring and process insulin poorly, creating what could be a human health conundrum — long lived people, but with greater potential for developing diabetes

As we quest for anti-aging drugs, the world is growing older anyway, surviving longer than ever before seen in modern times even without cracking the code of genes like klotho. A 2001 joint study by the U.S. Census Bureau and the National Institute on Aging called "An Aging World: 2001," predicts that this phenomenon of global aging will continue well into the 21st century, with the numbers and proportions of older people continuing to rise in both developed and developing worlds.

It says the world's 65 and older population is growing by an unprecedented 800,000 people a month and will continue to explode into the 21st century.

So before scientists can make synthetic klotho protein for possible life extension in people, there's more work ahead. "We still don't know everything about klotho protein function," Kuro-o says. "We know that klotho functions as a hormone but we still don't know where, how the hormone works on a cell. We haven't identified the klotho receptor."

Kuro-o says we shouldn't hang our hope on klotho: "Aging is a very complicated biological process so I don't believe that klotho is the only gene that regulates aging. Probably many other genes are involved in the regulation of aging and, of course, klotho cannot work alone."
All told, if we want to be like Oscar Wilde's fictional Dorian Gray — who lived without showing signs of aging — for now we may still have to make some bargains with the devil.

This research appeared in the Journal of Biological Chemistry, in November, 2005 (280: 38029-38034), and was funded by National Institutes of Health, National Institute of Aging, Pew Scholars Foundation, the UT Endowed Scholars Program and UT Southwestern Medical Center.

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