Seymour Benzer, Ph.D.
California Institute of Technology

Life extension genes in Drosophila.

Animals with longer lifespan usually have higher resistance to stress. The extended-lifespan Drosophila mutant methuselah resists all three different stresses tested, heat, starvation, and paraquat, an oxygen free radical generator. This suggests a molecular approach to identifying genes which are up-regulated by all three stresses, as candidates for longevity genes. The approach is to employ cDNA subtraction technique, using flies separately exposed to each of the stresses, and subtracting, by hybridization, the cDNA from unstressed flies, and to look for stress up-regulated genes. The converse subtraction would enrich for down-regulated genes. To find genes that are up regulated by all three stresses, stressed-minus-unstressed cDNA library was used to produce duplicate microarrays. These were separately hybridized with each of the other two kinds of stress-minus-unstressed cDNA probes. Clones showing positive results with both of the cDNA probes are candidates for genes that are up-regulated by all three different stresses. The positive clones are then to be checked by Northern blotting, to confirm whether they are up-regulated in flies subjected to the various stresses. The corresponding genes will be used to make transgenic flies to be tested for stress resistance and lifespan.

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