Genes, Mother Nature and Youth
By Doug Dollemore
Mother Nature is smarter than some scientists suspect. Take aging, for instance. It doesn't "just happen," says Cynthia Kenyon, a professor of biochemistry and biophysics at the University of California, San Francisco.
"Biologists often underestimate nature. They are always surprised by the order and logic of cells," Kenyon says. "For example, everyone was surprised by the 'intelligent' way that information is encoded in DNA. Aging was the same way. Many people considered aging to be an inevitable, passive process caused by the gradual corrosion of cellular components over time. The hourglass runs, and then it stops. For some years, I have felt that this view might be too simplistic, and that the aging process might be subject to regulation."
Dr. Cynthia Kenyon
To prove it, she has generated a slew of fundamental research that, in the next few decades, may help scientists determine if human aging can be slowed down through genetic alteration. Kenyon will discuss this once-unimaginable possibility when she delivers the Florence Mahoney Lecture on Aging, "Genes From the Fountain of Youth," at 3 p.m., Monday, Sept. 25, in Masur Auditorium, Bldg. 10. A reception will follow the lecture.
"Her studies have played a key role in initiating the modern molecular analysis of aging in model organisms," said Dr. Richard Hodes, director of the National Institute on Aging. "She is clearly a pioneer in a rapidly growing, exciting and productive research field."
Kenyon, who earned her Ph.D. at the Massachusetts Institute of Technology in 1981, began her research with a simple query: Why does a mouse live about 2 years and a bat about 50 years? Since these animals likely evolved from a common mammalian ancestor, she theorized that diversity in the lifespan of these and other animals arose from changes in genes that influence aging.
To test her hypothesis, she chose to study Caenorhabditis elegans, a tiny, self-replicating nematode or roundworm. C. elegans is useful for aging studies for several reasons: its genome has been deciphered; 70 percent of our genes have worm counterparts; and the worm has a relatively short lifespan (it achieves sexual maturity, produces about 300 progeny, ages and dies all in less than 3 weeks). These factors allow Kenyon to alter a single gene and, in just a few months, observe its impact through several generations of the worm. What she has found is C. elegans are "little gold mines of gene discovery.
"By changing certain genes, we can keep our animals young much longer than normal," Kenyon reported. "It's as if they have discovered the fountain of youth."
At least two genes, daf-2 and daf-16, appear to regulate aging in C. elegans. Daf-2 controls a special stage in the worm's development called dauer formation. A dauer forms if, in the first few hours of its brief life, a prepubescent worm finds food scarce. In this state, C. elegans grows a cuticle for protection and can go into hibernation for several months. When the food supply is ample again, the worm emerges from its dauer state and continues its normal lifecycle. Daf-2 is a gene that essentially drives the worm's development past or out of the dauer state. But Kenyon and her colleagues have found that daf-2 does much more. It also can regulate the lifespan of normal, fertile adults. By altering this gene so that its activity is reduced, Kenyon's team found lifespan of well-fed worms, who did not enter a dauer state, could be doubled.
"So we now know the worm has its own kind of death gene," Kenyon says. "In C. elegans, this gene, daf-2, speeds up the aging process. When its activity is inhibited, the worms live much longer and remain active and youthful for much longer than normal."
The daf-2 gene is similar to a gene in humans that functions in hormone control, she adds. In the worm, this gene makes a protein that looks much like the receptors for hormones such as insulin and IGF-1. In humans, these hormones control food utilization pathways, metabolism and cell growth.
Kenyon has recently found evidence that aging in the worms also may be regulated by hormonal changes in the reproductive and sensory organs. These discoveries may place aging in a similar category as hormonally triggered events such as puberty and menopause.
"This raises the question of whether there might be a simple hormonal treatment to retard aging in humans substantially," Kenyon said. "It is difficult for me to imagine that such an elaborate system evolved for nematodes alone. To me, it seems likely that a similar system regulates the life spans of higher organisms, possibly including humans. If so, someday we may be able to use this information to improve the quality of life of old age in humans. This would be a wonderful accomplishment. It is my goal."
Earlier this year, Kenyon was a recipient of the King Faisal International Prize for her studies of the aging process. She is a member of the American Academy of Arts and Sciences, and is an Ellison Foundation scholar.
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