SRA

Manipulating the activity of transcription factor (TF) to regulate animal's longevity is achieved in different species. However, deciphering the pro-longevity transcriptional programme triggered by the TFs activity is challenging. One obstacle is the multifunctional feature of TFs. The physiological functions of single TF could be diverse and tissues-dependent. The other is the gene regulatory network among the TFs, where multiple TFs can have synergetic or antagonistic impact on the same target genes. Here, we show Xbp1s overexpression in gut and fat body can extend lifespan in Drosophila. Importantly, Xbp1s activity triggers distinct transcriptional programmes in the two tissues, and Xbp1s induction in both tissues are beneficial for longevity. Furthermore, we reveal a pro-longevity gene regulatory network in the fat body, where Xbp1s and dFOXO impinge on the same target genes and induce identical transcriptional outcomes. dfoxo overexpression requires Xbp1 to extend lifespan. Lastly, inducing Xbp1u, the precursor of Xbp1s, can also extend lifespan without triggering massive transcriptome change. Overall design: S106>Xbp1s RU+/- S106>Xbp1u RU+/- S106>wdah RU+/- all conditions with gut and fat body samples