Drasticallyreducing calorie intake, or caloric restriction, is known to extend thelifespan of species including yeast, worms and rodents. Previousresearch linked a gene called Sir2 with lifespan extension due tocaloric restriction, but worms and yeast that lack Sir2 also livelonger when put on a tough diet, showing that some other genes must beat work.
Researchers led by David Sinclair at Harvard MedicalSchool and Su-Ju Lin at UC Davis' Center for Genetics and Developmentand Section of Microbiology screened for other life-extending genes inyeast. They found a gene called Hst2 that accounts for most of thedifference.
Deleting Hst2 and Sir2 blocked most of the beneficialeffect of caloric restriction. When Hst2 was overexpressed, so that thegene was more active than normal, the yeast lived longer than normal. Athird gene, Hst1, appears to act when both Sir2 and Hst2 are missing.
Sir2and the newly identified Hst genes account for all of thelife-prolonging effects of caloric restriction in yeast, Lin said.
Inyeast, the effects of aging seem to be due to a build-up of toxiccircular DNA molecules that accidentally get copied out of ribosomalDNA, an unstable area of the yeast genome that contains hundreds ofrepeated sequences.
The researchers showed that caloricrestriction drastically reduces recombination of ribosomal DNA, andthat deleting Hst2 and Sir2 blocks this effect.
Very similargenes are found in widely different animals including worms, flies androdents. But the targets of these genes are likely to be different, asthe toxic DNA circles have not been identified in more advancedorganisms, Lin said.
The work was published in the Sept. 16 issue of Science.
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