Philanthropy For Basic Science: Longevity Genes

The Regulation of Chromosomes and Longevity

DR. FRANKEL tested a series of mutations for effects upon longevity and aging in the fruit fly. He found that mutations that reduce expression of the Rpd3 histone deacetylase increase the lifespan of Drosophila by up to 47% for males and 52% for females. In these mutants, calorie restriction does not provide additional lifespan extension, suggesting that Rpd3 may be part of the caloric restriction pathway. This suggestion is reinforced by another of Dr. Frankel's findings: Wild-type flies fed low-calorie food and rpd3 mutants fed normal food both show over-expression of Sir2 histone deacetylase. Such Sir2 over-expression previously has been linked to lifespan extension in yeast and C. elegans. "Our results," Dr. Frankel wrote, "highlight the conservation of these systems of lifespan determination across distant species boundaries and suggest a simple pathway whereby calorie restriction affects longevity via the corepressor activities of Rpd3 and Sir2."