In 1993, Dr. Kenyon's discovery that a single-gene mutation could double the lifespan of C. elegans sparked an intensive study of the molecular biology of aging. Dr. Kenyon's findings have led to the discovery that an evolutionarily-conserved hormone signaling system influences aging in other organisms, including mammals. Kenyon has received many honors, including the King Faisal Prize for Medicine, the American Association of Medical Colleges Award for Distinguished Research, the Ilse & Helmut Wachter Award for Exceptional Scientific Achievement, and La Fondation IPSEN Prize, for her findings. She is a member of the U.S. National Academy of Sciences and the American Academy of Arts and Sciences. She is now the director of the Hillblom Center for the Biology of Aging at UCSF.
Cynthia Kenyon gives us an overview of her labs work:
"Aging and death are always with us. The sense of loss that comes with aging and death imbues the sonnets of Shakespeare, the stories of Oscar Wilde and the art of Cranach and others with great meaning and beauty. The idea of a fountain of youth is enchanting, but it has always been the stuff of fairy tales, not science. Scientists, too, think about aging, and they have been studying the aging process for a long time. But, like non-scientists, most of them have assumed that while it might be possible to live longer with a healthier lifestyle, nothing much could be done to fundamentally change the rate of aging.
Some of the most important discoveries in science have come not from studying people themselves, but from studying simpler creatures: bacteria, yeast, roundworms, fruit flies and mice. Although these animals look very different from one another and from people, they share universal mechanisms of life at the molecular level.
My lab has been studying a small microscopic roundworm called C. elegans for some time, and these animals are perfect for studies of aging because they get old and die in just a little over two weeks. What is more, it’s easy to look for genes that control virtually any process, simply by changing them (making mutations) and looking at the consequences.
It seemed to me that there was a good chance that the aging process, like so much else in biology, was not just a random and haphazard process but instead was subject to regulation by the genes. After all, rats live three years and squirrels can live for twenty-five, and these animals are different because of their genes. Also, most biological processes are subject to tight control by the genes. If so, then by finding genes that control aging, and then changing the activities of the proteins they encode, one day we might be able to stay young much longer than we do now.
When we began our studies of aging, in the early 1990s, one C. elegans gene that affected lifespan had been described, though it was poorly understood. When this gene was altered by a mutation, the animals lived 30-50% longer than normal. We looked for gene changes (mutations) that extended the lifespan of the roundworms, and we found that mutations in a gene called daf-2 doubled lifespan. These mutant worms still looked and acted young when they should be old. Seeing them was like talking to someone that looks 40 and learning that they were really 80. This was a stunning finding because no one thought it was possible. We also discovered another important gene, called daf-16, that was needed for this long lifespan. daf-16 was a gene that could keep an animal young.
We now know that these genes, daf-2 and daf-16, allow the tissues to respond to hormones that affect lifespan. We showed that daf-2 and daf-16 ultimately affect lifespan by influencing the activities of a wide variety of subordinate genes that influence the level of the body’s antioxidants, the power of its immune system, its ability to repair its proteins, and many other beneficial processes. We have found that the activity of the youthfulness gene daf-16 is influenced by signals from the environment and also by signals from within - from its reproductive system. This knowledge has now allowed us to extend the lifespan of active, youthful worms by six fold.
Others have now extended these findings to show that daf-2-like genes control the lifespan of fruit flies, mice and possibly (from studies that will be published soon) also humans. When these genes are changed, aging is slowed and lifespan is extended.
Especially wonderful is the fact that these long-lived animals are resistant to a variety of age related diseases, including (in various animals) cancer, heart failure, and protein-aggregation disease. Thus these mutants not only look young, they are young, in the sense that they are not susceptible to age-related disease until later. (Many people assume that if you could delay aging, you would just die of Alzheimer’s disease. We don’t know for sure, but this may not be true if ‘being elderly’ is what makes one susceptible to Alzheimer’s disease.) This link between aging and age-related disease suggests an entirely new way to combat many diseases all at once; namely, by going after their greatest risk factor: aging itself. This is an extremely exciting and important concept that could revolutionize medicine, human health and longevity, and it has just now begun to be studied in earnest, still in only a handful of labs.
Because it is very easy to look for genes affecting lifespan in C. elegans, we are continuing to do that in our lab. In fact, you can think of C. elegans as a ‘fountain of youthfulness genes’. We have identified about fifty genes so far that affect lifespan, and others have found this type of gene as well. More importantly, we are now using all the powerful molecular techniques available for studying this little animal to figure out just what these genes do to affect lifespan, so that we can apply that knowledge in a rational way. Whether these genes have universal effects on lifespan can now be tested in higher animals, where it is harder to discover lifespan genes starting from scratch. With all this new information, pharmaceutical and biotech companies can now make drugs that influence the activities of the proteins encoded by these genes, in hopes of combating age-related disease, and possibly aging itself, in humans. We don’t know yet, but to me it seems possible that a fountain of youth, made of molecules and not simply dreams, will someday be a reality."
To hear more from Cynthia Kenyon you can listen to her interview with Marc Pelletier on the webcast, Futures in Biotech 36: Avoiding Death, Not Taxes with Dr. Cynthia Kenyon Published on Nov 24, 2008
Host: Marc Pelletier Guest: Dr. Cynthia Kenyon; Professor, Department of Biochemistry and Biophysics, University of California San Francisco, Director of the Larry L. Hillblom Center for the Biology of Aging. We are back into a world leading lab to discuss the genetics of aging. Can it be controlled? You bet, and the implications are enormous. When these findings translate to the clinic, it will truly be a game changer for humanity.
You can also hear Cynthia Kenyon's American Society for Cell Biology iBio Seminar on Aging here:
Cynthia Kenyon, Mechanisms of Aging
And if you haven't seen it already, make sure to check out her discussion at the 2007 Aspen Health Forum: "Science vs the Biological Clock"
William Colby, Cynthia Kenyon and Stephanie Lederman all discuss the process of aging:
http://diybio4beginners.blogspot.com/2009/02/science-versus-biological-clock-video.html
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