Genetic analysis of the role of Cu/Zn SOD in aging and locomotor activity in Drosophila melanogaster

dc.contributor.advisorPhillips, John P.
dc.contributor.advisorHilliker, Arthur J.
dc.contributor.authorDickinson, Dale Alan
dc.date.accessioned2020-08-24T15:43:28Z
dc.date.available2020-08-24T15:43:28Z
dc.date.copyright1998
dc.degree.departmentDepartment of Molecular and Cellular Biologyen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameDoctor of Philosophyen_US
dc.description.abstractThe process of cellular respiration generates reactive oxygen species (ROS). Organisms have evolved defenses to remove ROS before they cause damage. The superoxide dismutases, which remove the superoxide anion O 2·-, are a key component of this defense system. The absence of Cu/Zn superoxide dismutase (SOD) activity in ' Drosophila' leads to pleitropic phenotypes, all believed to be the result of RO-mediated damage. Behavioral genetic analysis of motor activity clearly demonstrates decreases in locomotor activity in SOD-null mutants. It was further demonstrated that this decrease is not the result of a decreased metabolic rate as determined by the rate of oxygen consumption. While the absence of SOD has striking effects on lifespan and locomotor activity, heterozygous flies having reduced levels of SOD are indistinguishable from control flies with respect to lifespan, locomotor activity, and oxygen consumption. In wild-type SOD+ 'Drosophila', selectively overexpressing human 'SOD1' in their motorneurons increases lifespan, while studies of respiration rates in these flies reveal that this increase in lifespan is not due to a decrease in oxygen consumption or to a decrease in spontaneous locomotor activity. Taken together, the above results demonstrate the important role of SOD in the aging process, and strengthen the hypothesis that the nervous system plays a critical role in 'Drosophila' aging. In humans, missense mutations in 'SOD1' are associated with familial amyotrophic lateral sclerosis (FALS). However, the expression of known FALS allele ' G41S' in 'Drosophila' motorneurons did not affect lifespan, locomotor activity, or oxygen consumption, suggesting that motorneuron-limited expression of 'SOD' missense mutations may not be the primary cause of neurodegeneration. Mitochondrial DNA has been implicated as being a major molecular target for determining lifespan because, in every organism examined, the mtDNA accumulates partial deletions with increasing age. Examination of the mtDNA from ' Drosophila' revealed no partial deletions accumulating with age, or with the increased endogenous oxygen stress in SOD-null mutants. These results show that deletions in mtDNA are not a universal biomarker of aging.en_US
dc.identifier.urihttps://hdl.handle.net/10214/19631
dc.language.isoen
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectgenetic analysisen_US
dc.subjectCu/Zn SODen_US
dc.subjectsuperoxide dismutaseen_US
dc.subjectagingen_US
dc.subjectlocomotor activityen_US
dc.subjectDrosophila melanogasteren_US
dc.titleGenetic analysis of the role of Cu/Zn SOD in aging and locomotor activity in Drosophila melanogasteren_US
dc.typeThesisen_US

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