Abstract
Mutation of the human gene superoxide dismutase (hSOD1) is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig’s disease). Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila‘s motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF) as a function of age (5 to 50 days). Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking) behavior in late life when flies had lost the ability to fly (age ≥ 60 d). hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.
Highlights
Because both lifespan and behavior are affected by variation in genetic background, a number of genetic measures were taken in introducing the D42-GAL4 and UAS-hSOD1 transgenes into a uniform
The experiments described here provide data on functional abilities of a transgenic line of Drosophila melanogaster whose lifespan has been extended by overexpression of the human gene hSOD1 in motorneurons
We found that female hSOD1 flies were able to sustain continuous flight longer than control females
Summary
Drosophila melanogaster is an important animal model in the study of aging, life-extension, and functional decline, partly because of its short lifespan of approximately two months, which facilitates population-level studies of changes in behavior and physiology at various stages of life, and partly because of the high homology of its genes to other species including mammals (Rose et al, 1992; Curtsinger et al, 1995; Osiewacz, 1997; Parkes et al, 1998; Phillips et al, 2000). Increased longevity by hSOD1 overexpression is thought to occur by antioxidant intervention that mitigates cumulative DNA and cell damage caused by reactive oxygen species (Harman, 1956, 2003; Martin et al, 1996). This process is thought to be further mediated by hSOD1-triggered changes in signal transduction pathways, possibly through the neuroendocrine system, that regulate patterns of gene expression in a variety of aerobic cell types other than motorneurons (Phillips et al, 2000)
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