title: LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis.
abstract: The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN-28/let-7/AKT/DAF-16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level-a central dogma of the 'evolutionary optimization' of resource allocation that modulates aging.
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.|University of Chinese Academy of Science, Beijing, 100049, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne, 50931, Germany.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Su
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Weiyang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.|University of Chinese Academy of Science, Beijing, 100049, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Green
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu, 210061, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne, 50931, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.affiliation: Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Jing-Dong J
authors.initials: JJ
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002452:Cell Count; D049109:Cell Proliferation / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D005854:Germ Cells / Q000166:cytology*; D006358:Hot Temperature; D008136:Longevity / Q000502:physiology* / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D013312:Stress, Physiological / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins
keywords: 
  Caenorhabditis elegans
  ; DAF-16; LIN-28; let-7; longevity; reproduction