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.