Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in...

Transposable elements (TEs) are mobile sequences of DNA that can become transcriptionally active as an animal ages. Whether TE activity is simply a by-product of heterochromatin breakdown or can contribute toward the aging process is not known. Here, we place the TE gypsy under the control of the UAS GAL4 system to model TE activation during aging. We find that increased TE activity shortens the life span of male Drosophila melanogaster. The effect is only apparent in middle-aged animals. The increase in mortality is not seen in young animals. An intact reverse transcriptase is necessary for the decrease in life span, implicating a DNA-mediated process in the effect. The decline in life span in the active gypsy flies is accompanied by the acceleration of a subset of aging phenotypes. TE activity increases sensitivity to oxidative stress and promotes a decline in circadian rhythmicity. The overexpression of the Forkhead-box O family (FOXO) stress response transcription factor can partially rescue the detrimental effects of increased TE activity on life span. Our results provide evidence that active TEs can behave as effectors in the aging process and suggest a potential novel role for dFOXO in its promotion of longevity in D. melanogaster.