Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system
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The GADD45 protein family plays an important role in stress signaling and participates in the integration of cellular response to environmental and physiological factors. GADD45 proteins are involved in cell cycle control, DNA repair, apoptosis, cell survival and aging, and inflammatory response by complicated protein–protein interactions. In Drosophila melanogaster a single D-GADD45 ortholog (GG1086) has been described. Our data show that overexpression of the D-GADD45 gene in the nervous system leads to a significantly increase of Drosophila lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females, which agrees with the sex-dependent expression of this gene. The longevity of D. melanogaster with D-GADD45 overexpression is apparently due to more efficient recognition and repair of DNA damage, as the DNA comet assay showed that the spontaneous DNA damage in the larva neuroblasts is reduced with statistical significance.
KeywordsAging Longevity Stress response Stress signaling GADD45 Nervous system
We thank the Institute of Biology of Aging and the “Science for Life Extension” Foundation for financial support of the project. We are also grateful to Dr. Uri Abdu (Ben-Gurion University, Israel), Dr. Haig Keshishian (Yale University, New Haven, USA), and the Drosophila Stock Center (Indiana University, Bloomington, Indiana, USA) for providing the D. melanogaster laboratory strains. We thank postgraduate students I. Velegzhaninov, O. Malysheva, E. Romanova and students D. Chernyshova, V. Mezentseva and A. Danilov for their technical assistance, and V. Artyuchov for the help with manuscript translation into English.
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