Mutations in dSir2 block the life-span-extending effect of rpd3 mutants. The extension in life span seen with rpd3 mutation was prevented by mutations in dSir2. Flies labeled as “rpd3” are heterozygous for the rpd3def24-null allele of rpd3, whereas flies labeled as “dSir2 and rpd3” possess one copy of the life-span-extending rpd3-null mutation and one copy of either the dSir217-null (28) or dSir2EP2300-hypomorphic allele. (a) dSir217. Flies labeled “rpd3,” “dSir2 and rpd3,” and “control” were each backcrossed to a Canton-S background. (b) dSir2EP2300. Flies labeled “rpd3,” “dSir2 and rpd3,” and “control” were collected from the offspring of crosses between the rpd3-null allele, rpd3def24, and dSir2EP2300. Flies labeled “control” were derived from an additional cross to remove the rpd3 and dSir2EP2300 alleles and any balancer chromosomes. Each life span included at least 200 male and 200 female flies (16).