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Activation of transposable elements during aging and neuronal decline in Drosophila

Abstract

We found that several transposable elements were highly active in Drosophila brain during normal aging. In addition, we found that mutations in Drosophila Argonaute 2 (Ago2) resulted in exacerbated transposon expression in the brain, progressive and age-dependent memory impairment, and shortened lifespan. These findings suggest that transposon activation may contribute to age-dependent loss of neuronal function.

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Figure 1: Age-dependent increases in expression of LINE-like and LTR retrotransposons in Drosophila brain.
Figure 2: gypsy-TRAP reporter detects de novo integration in neurons in aged flies.
Figure 3: Age-dependent transposable element expression contributes to memory decline and age-dependent mortality.

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Acknowledgements

We thank B. Czech and G. Hannon (Cold Spring Harbor Laboratory) for the Ago2414 and loki RNAi fly lines, F.-B. Gao (University of Massachusetts Medical School) for the Ago251B fly line, B. Dickson (Institute of Molecular Pathology) for the UASAgo2 transgenic fly line, M. Welte (University of Rochester) for the Ago2454 fly line, T. Lee (Janelia Farm Research Campus) for the pTub-GAL80 in Casper4 plasmid, J. Boek (Johns Hopkins University School of Medicine) for the 7B3 hybridoma cell line, and C. Bautista at the Cold Spring Harbor Laboratory shared resources for ascites production. We thank T. Russel for technical assistance in construction of the gypsy reporter system. We also are grateful to S. Waddell, J. Beshel, M. Cressy, B. Czech, G. Hannon, K. Honegger, J. Huang, M. Kernan, R. Martienssen, H. Qin, C. Sandoval, Y. Shuai, G. Turner, T. Zador and Y. Zhong for helpful discussions or comments on the manuscript. This work was supported by US National Institutes of Health grant TR01(5R01NS067690-03) and DART NeuroScience LLC awarded to J.D. S.G. received additional support from the Shakespeare Fellowship and the Ernst Göhner Foundation.

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W.L., L.P. and J.D. conceived and designed the project and analyzed the experiments. W.L. performed the behavior experiments and western blots. The QPCR and lifespan analyses were performed by L.P. with assistance from W.L., L.K. and D.T. L.P., N.C. and S.G. did the imaging. W.L., L.P. and J.D. wrote the manuscript with comments from the other authors.

Corresponding author

Correspondence to Josh Dubnau.

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Competing interests

This work was funded in part by DART NeuroScience LLC via a research grant to J.D.

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Supplementary Figures 1–7 and Supplementary Tables 1 and 2 (PDF 9582 kb)

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Li, W., Prazak, L., Chatterjee, N. et al. Activation of transposable elements during aging and neuronal decline in Drosophila. Nat Neurosci 16, 529–531 (2013). https://doi.org/10.1038/nn.3368

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