This video segment adapted from NOVA scienceNOW examines how a gene called FOXO affects life span. Researcher Cynthia Kenyon at the University of California, San Francisco, increased the activity of a single FOXO gene in the microscopic worm C. elegans and doubled the worm's life span. FOXO regulates about 100 other genes that protect an organism's cells and tissues. Researchers Bradley Willcox and Timothy Donlon found that FOXO performs a similar role in humans. People who possess a single copy of the protective version of the gene are twice as likely to live to the age of 100, while those with two copies have triple the chance.
When Jeanne Calment of France died in 1997, at the age of 122, she was the oldest person to have ever lived. That milestone may soon be surpassed, however, as more and more people are living to 100 because of improved health, nutrition, medicine, and safety. Genetics plays a vital role in the mechanisms of aging, age-related diseases, and longevity. But why some people live to extreme old age, while remaining physically and mentally active, is unknown. The recent discovery—in worms, mice, fruit flies, and humans—of a family of genes called FOXO may help answer the question.
In experiments with worms, increasing the activity of the FOXO gene resulted in a doubling or more of life span. In addition, the worms remained active and youthful well into old age. (Note: Invertebrates have only one FOXO gene while mammals have four.)
Aging is caused in part by the accumulation of damage to cells and DNA over time, both from environmental impacts and from normal cell processes. When cells divide and reproduce, DNA is copied, and errors, or mutations, can occur. Thus, the longer that cell division has been going on, the more mutations will accumulate in the DNA. This can lead to age-related diseases such as cancer.
Scientists found that FOXO increases longevity by repairing cells and keeping them in good working order for longer. FOXO genes (named for the characteristic forked-head box structure of the proteins they produce) carry instructions for making proteins called transcription factors that turn other genes on and off. FOXO acts like a conductor cuing musicians in an orchestra to start or stop playing. FOXO can cue genes to increase the rate of cell repair, ramp up the immune system, or suppress tumor growth, keeping the organism healthier longer.
So far, FOXO genes have been found to play a critical role in embryo development, cell division and proliferation, metabolism, stress tolerance, tumor suppression, and the function of the cardiovascular, digestive, and immune systems—all of which affect life span. Given the discoveries so far, it is likely FOXO genes will eventually be found to impact most if not all systems and functions.
Twenty-five percent of humans carry one copy of the protective version of the FOXO gene, and these people are twice as likely to live to 100. The lucky 10 percent who inherit two copies of the protective version are three times as likely to achieve centenarian status.
However, people without the protective version of FOXO can still have a long and healthy life, as genetics alone does not control longevity. Diet, exercise, and environmental factors all play a large and important role.
The discovery of a few genes that control many aspects of aging and longevity suggests a revolutionary new way to combat the diseases of old age. Instead of fighting cancer, diabetes, and heart disease directly, doctors might instead treat the underlying condition of aging itself by turning on genes that keep us healthier longer.
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