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Published on: June 27, 2016
Overexpression of methionine-R-sulfoxide reductases has no influence on fruit fly aging
Valentina A Shchedrina1, Gerd Vorbrüggen, Byung Cheon Lee
1Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.
Abstract:
Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antioxidant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under calorie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized in animal model systems. Here, the GAL4-UAS binary system was used to drive overexpression of cytosolic Drosophila MsrB and mitochondrial mouse MsrB2 in whole body, fatbody, and the nervous system of flies. In contrast to MsrA, MsrB overexpression had no consistent effect on the lifespan of fruit flies on either corn meal or sugar yeast diets. Physical activity, fecundity, and stress resistance were also similar in MsrB-overexpressing and control flies. Thus, MsrA and MsrB, the two proteins with similar function in antioxidant protein repair, have different effects on aging in fruit flies.
Insights
Methionine sulfoxide reductases (Msrs) are key to antioxidant defense. Unlike MsrA, MsrB overexpression did not consistently affect fruit fly lifespan or other aging markers.
Area of Science:
- Biochemistry
- Molecular Biology
- Gerontology
Background:
- Methionine sulfoxide reductases (Msrs) are crucial enzymes for repairing oxidized methionine residues in proteins.
- Msrs play a role in antioxidant defense and aging regulation, with two types in animals: MsrA and MsrB.
- Previous studies showed MsrA overexpression extends lifespan in Drosophila and yeast, but MsrB's effect in animal models remained uncharacterized.
Purpose of the Study:
- To investigate the effect of MsrB overexpression on lifespan and aging parameters in a fruit fly model.
- To compare the impact of MsrB with previously observed effects of MsrA on aging.
Main Methods:
- Utilized the GAL4-UAS binary system to overexpress cytosolic Drosophila MsrB and mitochondrial mouse MsrB2.
- Overexpression was targeted to the whole body, fat body, and nervous system of Drosophila.
- Assessed lifespan, physical activity, fecundity, and stress resistance in MsrB-overexpressing flies compared to controls.
Main Results:
- Overexpression of MsrB in fruit flies did not consistently affect lifespan across different diets (corn meal or sugar yeast).
- No significant differences were observed in physical activity, fecundity, or stress resistance between MsrB-overexpressing and control flies.
- These findings contrast with the lifespan extension previously observed with MsrA overexpression.
Conclusions:
- MsrA and MsrB, despite similar functions in protein repair, exhibit distinct effects on aging in fruit flies.
- MsrB overexpression does not appear to influence key aging parameters in this animal model.
- The differential impact of MsrA and MsrB highlights specific roles in the aging process.
