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A Gene Involved in Regulating Longevity in Worms May Provide a Clue to Human Aging

NIH/National Institute on Aging

Gene for Regulating Longevity

Discovery of a mutant gene involved in the regulation of longevity of a primitive worm, C. elegans, may provide a clue as to how humans age. Normal development and longevity in the worm C. elegans are regulated by the age-1 gene. Lack of age-1 activity in adult worms, due to mutations in the age-1 gene, results in a doubling of adult life span. The research team of Drs. Gary Ruvkun, Jason Morris, and Heidi Tissenbaum at Massachusetts General Hospital/Harvard Medical School isolated and determined the DNA sequence of the normal and four mutant forms of the C.elegans age-1 gene. Further analysis revealed that the normal age-1 gene encodes the worm homolog of the enzyme phosphotidyl-inositol-3-OH-kinase (PI(3)K), a key biological mediator of cellular communication and signal transduction. This study, published in the August 8, 1996 issue of Nature, was supported by the National Institute on Aging (NIA).

Analysis of animals with several different mutations in the age-1 gene showed that the AGE-1 PI(3)K protein functions specifically in the longevity pathway in C. elegans. The authors speculate that lower levels of PI(3)K activity may trigger a biochemical program in the worm, ultimately leading to a decreased rate of aging and senescence. However, they caution that it is not yet known whether phosphotidylinositol-mediated control of longevity is confined to C.elegans or is more generally applicable to regulation of aging and longevity in mammalian species including humans.

Dr. Anna McCormick, Chief of the Biology Branch of the NIA Biology of Aging Program, is available to comment on the recent cloning of the age-1 gene and the relationship of age-1 to human aging and longevity. To schedule an interview with Dr. McCormick, contact the NIA Public Information Office at (301) 496-1752 or e-mail Claudia Feldman at

The NIA, National Institutes of Health, leads the Federal effort in the study of the biology of aging and the special needs of older people.

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