Abstract
Transposable elements (TE) are mobile sequences of DNA that can become transcriptionally active as an animal ages. Activation of the stress response transcription factor FOXO can increase longevity in flies and worms. Research into the subject has centered on metabolism as the driver of aging. Whether TE activity is a byproduct of heterochromatin breakdown or can contribute towards the aging process is not known. Neither is the potential effect of FOXO on TE activity during aging. Here we examine dFOXO’s effect on TE during aging by using next sequencing approaches and find that the TE landscape is a caveat to determining whether there is a dFOXO effect. We place the TE gypsy under the control of the UAS GAL4 system to model TE activation during aging and circumvent the TE landscape caveat. We find that TE activity can shorten the lifespan of male D. melanogaster and the mortality defect is only apparent after middle age. The increase in mortality is not present in the reverse transcriptase mutants, indicating an intact reverse transcriptase is necessary for the decrease in lifespan. The decline in lifespan 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 TE activity on lifespan. Our results provide evidence that active TE can behave as effectors in the aging process and suggest a potential novel role for dFOXO to promote longevity in D. melanogaster.