Gene mutation extends lifespan in 'I'm not dead yet' fruitflies

December 13, 2000

Mutating a single gene can double the lifespan of fruitflies from 37 days to between 69 and 71 days, while maintaining a high level of functioning and fertility. This finding of a research team led by Stephen L. Helfand was supported in part by the National Institute on Aging (NIA), part of the National Institutes of Health.* Their study is reported in the December 14 issue of Science. The gene complex was named Indy as a joking reference to the tag line from Monty Python and the Holy Grail, "I'm not dead yet." This is the third mutation in the fruitfly genome that is reported to extend lifespan. According to Helfand, the Indy gene is associated with the way that the body stores and uses energy.

The gene is named "Indy" in homage to Monty Python and the Holy Grail's tag line, "I'm not dead yet," uttered by a supposed plague victim being hauled off for burial while still alive. (JPEG file available on request.)

The researchers speculate that the way the Indy gene mutation works to extend life and health may be via changes in the normal metabolism of food. This link between altered metabolism and life-span extension became the focus of Helfand's studies when other laboratories showed that research animals receiving full nutrition but lowered calorie intake, or caloric restriction, lived longer. Although the mechanism by which caloric restriction benefits longevity is not understood, Dr. Helfand suggests that it is likely to involve changes in energy utilization. The Indy fruitfly differs from other long-lived fruitflies by the direct, rather than indirect, action of the altered gene on metabolism and the use of food energy.

"What is interesting about this line of research is the recurrence of the link between metabolism, caloric restriction and longevity. This study points to the possibility that if you genetically alter metabolism, you can alter lifespan," said Dr. David Finkelstein, research director for metabolic regulation research at the National Institute on Aging.

"While there is an 80 percent homology between the fruitfly and human genomes, we are still many steps away from understanding how caloric restriction may affect human lifespan," Finkelstein said.
The NIA leads the federal effort in supporting and conducting basic and clinical research on aging and the special needs of older people. For information about the NIA, visit the website at

* The work of Stephen L. Helfand, Blanka Rogina, Robert A. Reenan, and Steven P. Nilsen was funded by the National Institute on Aging through investigator-supported grants, as well as a grant to the Claude D. Pepper Older Americans Independence Center, University of Connecticut. The UCONN Pepper Center, one of 10 nationwide, is devoted to enhancing the independence of older persons through research, research training, and dissemination of new findings. At Pepper Centers, translational and basic scientists participate in studies linking molecular mechanisms with clinical interventions.

NIH/National Institute on Aging

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