Stephen Helfand, M.D.
University of Connecticut Health Center

Genetic Dissection of Aging in Drosophila.

Single gene mutagenesis is a powerful method for dissecting complex biological phenomena such as aging. It has been used with great success in developmental biology. One advantage, for aging research in particular, is that it does not require detailed knowledge of the mechanisms that control life span. The identification of single gene mutations that extend life span may provide a direct link demonstrating how alterations in statement of individual genes may extend life span. Life extending gene alterations may provide specific targets for therapeutic interventions as well as insight into which physiological systems are most important in aging. A strength of this approach, especially in Drosophila, lies in the powerful molecular and genetic methods which allow the rapid identification and testing of genetic loci of interest.

There are at least two major problems that have delayed the isolation of long-lived mutants in complex organisms. The first is the concern that single gene alterations that extend life span without a loss in activity or fertility will not be found in complex organisms such as Drosophila. The isolation of long lived mutants methuselah and Indy in the Benzer and Helfand laboratories respectively remove the obstacle. The second obstacle is a lack of an accepted surrogate phenotype for assessing life span other than survivorship itself--which is prohibitively time-consuming. We are combining our previous work on temporal patterns of gene statement in the fly with a novel method of selection to create a system of rapidly selecting for single gene alterations that extend life span.

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