Figure 1
Tissue interplay that regulates lifespan. (a) Genes that mediate germline elimination-induced lifespans in C. elegans. Germline elimination enhances the steroid signal dafachronic acid, which is produced in somatic gonads. DAF-12 regulates the expression of mir-84 and mir-241, and increased mir-84 and mir-241 expression results in the downregulation of two DAF-16 inhibitors (AKT-1 and LIN-14) and promotes DAF-16 nuclear localization and activation. Germline elimination also activates the transcription factors PHA-4, HLH-30 and NHR-80. The activation of these transcription factors leads to changes in fatty acid metabolism, as well as enhanced autophagy and proteasome activity. (b) The genetic manipulations in neuronal cells are sufficient for increasing organismal lifespan. The RNAi of cco-1 or overexpression of xbp-1, aak-2, hsf-1 or hif-1 extends lifespans by regulating other tissues. (c) Intestinal DAF-16 regulates both DAF-16 and a non-DAF-16 transcription factor (referred to as X here) in other tissues via INS-7- and MDT-15-dependent lipid signals, respectively.
