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Science 338 (6113): 1472-1476

Copyright © 2012 by the American Association for the Advancement of Science

A Steroid Receptor–MicroRNA Switch Regulates Life Span in Response to Signals from the Gonad

Yidong Shen,1,2 Joshua Wollam,1,2 Daniel Magner,1,2 Oezlem Karalay,1 Adam Antebi1,2,3,*

Abstract: 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.

1 Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, D-50931 Cologne, Germany.
2 Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
3 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, D-50674 Cologne, Germany.

* To whom correspondence should be addressed. E-mail: antebi{at}age.mpg.de

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