A steroid receptor–microRNA switch regulates life span in response to signals from the gonad

Y Shen, J Wollam, D Magner, O Karalay, A Antebi - Science, 2012 - science.org
Y Shen, J Wollam, D Magner, O Karalay, A Antebi
Science, 2012science.org
Although the gonad primarily functions in procreation, it also affects animal life span. Here,
we show that removal of the Caenorhabditis elegans germ line triggers a switch in the
regulatory state of the organism to promote longevity, co-opting components involved in
larval developmental timing circuits. These components include the DAF-12 steroid receptor,
which is involved in the larval stage two–to–stage three (L2-L3) transition and up-regulates
members of the let-7 microRNA (miRNA) family. The miRNAs target an early larval nuclear …
Although the gonad primarily functions in procreation, it also affects animal life span. Here, we show that removal of the Caenorhabditis elegans germ line triggers a switch in the regulatory state of the organism to promote longevity, co-opting components involved in larval developmental timing circuits. These components include the DAF-12 steroid receptor, which is involved in the larval stage two–to–stage three (L2-L3) transition and up-regulates members of the let-7 microRNA (miRNA) family. The miRNAs target an early larval nuclear factor lin-14 and akt-1/kinase, thereby stimulating DAF-16/FOXO signaling to extend life. Our studies suggest that metazoan life span is coupled to the gonad through elements of a developmental timer.
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