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

被引：80

作者：

Shen, Yidong ^{[1
,2
]}

Wollam, Joshua ^{[1
,2
]}

Magner, Daniel ^{[1
,2
]}

Karalay, Oezlem ^{[1
]}

Antebi, Adam ^{[1
,2
,3
]}

机构：

[1] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

[2] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[3] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany

来源：

SCIENCE | 2012年 / 338卷 / 6113期

关键词：

STEM-CELLS; LONGEVITY; DAF-16;

D O I：

10.1126/science.1228967

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1472 / 1476

页数：6

共 21 条

[1] Regulation of life-span by germ-line stem cells in Caenorhabditis elegans [J].

Arantes-Oliveira, N ;

Apfeld, J ;

Dillin, A ;

Kenyon, C .

SCIENCE, 2002, 295 (5554) :502-505

[2] Germ-cell loss extends C-elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling [J].

Berman, JR ;

Kenyon, C .

CELL, 2006, 124 (05) :1055-1068

[3] Nuclear Hormone Receptor Regulation of MicroRNAs Controls Developmental Progression [J].

Bethke, Axel ;

Fielenbach, Nicole ;

Wang, Zhu ;

Mangelsdorf, David J. ;

Antebi, Adam .

SCIENCE, 2009, 324 (5923) :95-98

[4] A developmental timing microRNA and its target regulate life span in C. elegans [J].

Boehm, M ;

Slack, F .

SCIENCE, 2005, 310 (5756) :1954-1957

[5] The C. elegans MicroRNA mir-71 Acts in Neurons to Promote Germline-Mediated Longevity through Regulation of DAF-16/FOXO [J].

Boulias, Konstantinos ;

Horvitz, H. Robert .

CELL METABOLISM, 2012, 15 (04) :439-450

[6] Drosophila, germ-line modulation of insulin signaling and lifespan [J].

Flatt, Thomas ;

Min, Kyung-Jin ;

D'Alterio, Cecilia ;

Villa-Cuesta, Eugenia ;

Cumbers, John ;

Lehmann, Ruth ;

Jones, D. Leanne ;

Tatar, Marc .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (17) :6368-6373

[7] A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling [J].

Gerisch, Birgit ;

Rottiers, Veerle ;

Li, Dongling ;

Motola, Daniel L. ;

Cummins, Carolyn L. ;

Lehrach, Hans ;

Mangelsdorf, David J. ;

Antebi, Adam .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (12) :5014-5019

[8] Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans [J].

Goudeau, Jerome ;

Bellemin, Stephanie ;

Toselli-Mollereau, Esther ;

Shamalnasab, Mehrnaz ;

Chen, Yiqun ;

Aguilaniu, Hugo .

PLOS BIOLOGY, 2011, 9 (03)

[9] A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans [J].

Hammell, Christopher M. ;

Karp, Xantha ;

Ambros, Victor .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (44) :18668-18673

[10] mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts [J].

Hammell, Molly ;

Long, Dang ;

Zhang, Liang ;

Lee, Andrew ;

Carmack, C. Steven ;

Han, Min ;

Ding, Ye ;

Ambros, Victor .

NATURE METHODS, 2008, 5 (09) :813-819

← 1 2 3 →