Genes Found That Extend Lifespan

Significantly reducing calorie intake, or caloric restriction, is known to extend the lifespan of organisms including yeast, worms, and rodents. Earlier studies tied a gene called Sir2 with lifespan extension caused by caloric restriction, but yeast and worms that lack Sir2 also live longer when put on a restricted diet, demonstrating that some other genes must be at work.

Researchers led by Dr. David Sinclair at Harvard Medical School (Boston, MA, USA) and Dr. Su-Ju Lin from the University of California, Davis, Center for Genetics and Development and Section of Microbiology (UC Davis; USA) screened for other life-extending genes in yeast. They discovered a gene called Hst2 that accounts for most of the discrepancy.

Deleting Hst2 and Sir2 blocked most of the beneficial effect of caloric restriction. When Hst2 was overexpressed, so that the gene was more active than normal, the yeast lived longer than normal. A third gene, Hst1, seems to function when both Sir2 and Hst2 are missing. Sir2 and the newly found Hst genes account for all of the life-extending effects of caloric restriction in yeast, according to Dr. Lin.

In yeast, the effects of aging seem to be caused by an accumulation of toxic circular DNA molecules that mistakenly get copied out of ribosomal DNA, an unstable region of the yeast genome that contains hundreds of repeated sequences. The investigators showed that caloric restriction dramatically reduces recombination of ribosomal DNA, and that deleting Hst2 and Sir2 stops this process.

Very similar genes are found in broadly diverse animals including worms, flies, and rodents. However, the targets of these genes are likely to be different, as the toxic DNA circles have not been identified in more sophisticated organisms, according to Dr. Lin.

The study was published in the September 16, 2005, issue of the journal Science.






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