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

Authors: Shen Y; Wollam J; Magner D; Karalay O; Antebi A

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.

Keywords: Animals; Caenorhabditis elegans/genetics/growth & development/*physiology; Caenorhabditis elegans Proteins/genetics/*physiology; Gene Expression Regulation, Developmental; Germ Cells/metabolism; Gonads/*metabolism; Larva/genetics/growth & development/physiology; Longevity/genetics/*physiology; MicroRNAs/genetics/*metabolism; Nuclear Proteins/genetics/physiology; Proto-Oncogene Proteins c-akt/genetics/physiology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Receptors, Steroid/genetics/*physiology; Signal Transduction; Transcription Factors/genetics/physiology
Journal: Science (New York, N.Y.)
Volume: 338
Issue: 6113
Pages: 1472-6
Date: Dec. 15, 2012
PMID: 23239738
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Citation:

Shen Y, Wollam J, Magner D, Karalay O, Antebi A (2012) A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science (New York, N.Y.) 338: 1472-6.


Study Lifespan Factors:
  • Germline


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