Proceedings of the National Academy of Sciences · 2002 · 453 citations · 43 references
Life SciencesBiologyNeuroscienceAgingMolecular NeurobiologyMolecular NeuroscienceAging PhysiologyBiological AgingCellular SenescenceLongevityOxidative Damage To BiomoleculesOxidative StressDrosophila ModelsLife ExtensionMethionine MetabolismMethionine OxidationPhysiological AgingSenescenceTransgenic AnimalsTransgenic Drosophila
Cumulative oxidative damages to cell constituents are considered to contribute to aging and age-related diseases. The enzyme peptide methionine sulfoxide reductase A (MSRA) catalyzes the repair of oxidized methionine in proteins by reducing methionine sulfoxide back to methionine. However, whether MSRA plays a role in the aging process is poorly understood. Here we report that overexpression of the msrA gene predominantly in the nervous system markedly extends the lifespan of the fruit fly Drosophila. The MSRA transgenic animals are more resistant to paraquat-induced oxidative stress, and the onset of senescence-induced decline in the general activity level and reproductive capacity is delayed markedly. The results suggest that oxidative damage is an important determinant of lifespan, and MSRA may be important in increasing the lifespan in other organisms including humans.
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Aging: A Theory Based on Free Radical and Radiation Chemistry
Denham Harman · Journal of Gerontology · 1956 · 8.5K citations
Natural Sciences, Chemistry, Aging +16
A C. elegans mutant that lives twice as long as wild type
Cynthia Kenyon, Jean Chang, Erin Gensch et al. · Nature · 1993 · 3.4K citations
Life Sciences, Biology, Genetics +6