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Comparative Study
. 2003 Apr;2(2):123-30.
doi: 10.1046/j.1474-9728.2003.00044.x.

Testing an 'Aging Gene' in Long-Lived Drosophila Strains: Increased Longevity Depends on Sex and Genetic Background

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Free PMC article
Comparative Study

Testing an 'Aging Gene' in Long-Lived Drosophila Strains: Increased Longevity Depends on Sex and Genetic Background

Christine C Spencer et al. Aging Cell. .
Free PMC article

Abstract

Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived. However, the mutant's high-longevity phenotype may be dependent on interactions with alleles that are common in short-lived laboratory strains. Here we set out to determine whether one particular mutant could extend lifespan in long-lived genetic backgrounds in the fruit fly, Drosophila melanogaster. We measured longevity and resistance to thermal stress in flies that were transgenically altered to overexpress human superoxide dismutase (SOD) in the motorneurones in each of 10 genotypes. Each genotype carried the genetic background from a different naturally long-lived wild-caught Drosophila strain. While SOD increased lifespan on average, the effect was genotype- and sex-specific. Our results indicate that naturally segregating genes interact epistatically with the aging gene superoxide dismutase to modify its ability to extend longevity. This study points to the need to identify mutants that increase longevity not only in the lab strain of origin but also in naturally long-lived genetic backgrounds.

Figures

Fig. 1
Fig. 1
Genotypes for overexpression and control levels of superoxide dismutase (SOD). (a) Genotype of UAS-HS control and overexpression flies obtained from Parkes et al. (1998) containing two P-elements. The P(w+)UAS-hSOD1 insert on the second chromosome carries a GAL4-sensitive upstream activating sequence and a human SOD1 gene. On the third chromosome, P[GAL4] is expressed only in adult motorneurones, thereby activating expression of the hSOD1 gene. (b) The UAS-HS overexpression strain used at UGA was homozygous for the hSOD1 P-element. The third chromosome carries GAL4 and a null mutation (X39) at the Drosophila SOD locus; it is balanced to prevent recombination. The control strain lacks GAL4. (c) Experimental strains result from a cross between UAS-HS males from b and females from 10 recently wild-caught, inbred isofemale strains. Here, + represents wild-caught wild-type alleles. The first three chromosomes of D. melanogaster are shown. Male genotypes are given in a and b; female genotypes are given in c. Numbers on the right represent the number of Drosophila SOD and human SOD alleles being expressed for each genotype. w = white, P = P-element, + = wild-type.
Fig. 2
Fig. 2
Life expectancy. Female (a) and male (b) mean lifespan in days for control (open bars) and SOD overexpressed (shaded bars) genotypes from the UGA UAS-HS control strains and 10 wild-caught, inbred genetic backgrounds. Bars are +1 standard error. *P < 0.05, **P < 0.005.
Fig. 3
Fig. 3
Correlation between the sexes of the change in lifespan caused by SOD overexpression. Correlation by sex of the change in mean lifespan between SOD overexpression and control flies within each genetic background. Data are mean difference in days for each genetic background.
Fig. 4
Fig. 4
Thermal tolerance for experimental lines. Thermal tolerance in female (a) and male (b) controls and 10 wild-caught, inbred genetic backgrounds for SOD control and SOD overexpression genotypes. Error bars are +1 standard error.

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