Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity

Details

• Alternative Title:
  Cell Rep
• Personal Author:
  Lan, Jianfeng ; Rollins, Jarod A. ; Zang, Xiao ; Wu, Di ; Zou, Lina ; Wang, Zi ; Ye, Chang ; Wu, Zixing ; Kapahi, Pankaj ; Rogers, Aric N. ; Chen, Di
• Description:
  Reduced mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension in C. elegans. To understand the roles of translational regulation in this process, we performed polysomal profiling and identified translationally regulated ribosomal and cytochrome c (CYC-2.1) genes as key mediators of longevity. cyc-2.1 knockdown significantly extends lifespan by activating the intestinal mitochondrial unfolded protein response (UPR|), mitochondrial fission, and AMP-activated kinase (AMPK). The germline serves as the key tissue for cyc-2.1 to regulate lifespan, and germline-specific cyc-2.1 knockdown non-autonomously activates intestinal UPR| and AMPK. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cyc-2.1 in the germline is important for the non-autonomous activation of UPR| and synergistic longevity of the daf-2 rsks-1 mutant. Altogether, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.
• Subjects:
  Article
• Source:
  Cell Rep. 28(4):1050-1062.e6
• Pubmed ID:
  31340143
• Pubmed Central ID:
  PMC6684276
• Document Type:
  Journal Article
• Funding:
  R01 AG045835/NIA NIH HHS/National Institute on Aging/United States ; R21 AG056743/NIA NIH HHS/National Institute on Aging/United States ; P40 OD010440/ODCDC CDC HHS/Office of the Director/United States ; R21 AG053066/NIA NIH HHS/National Institute on Aging/United States ; P20 GM104318/NIGMS NIH HHS/National Institute of General Medical Sciences/United States ; P20 GM103423/NIGMS NIH HHS/National Institute of General Medical Sciences/United States
• Volume:
  28
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7ac2a88ccb39b4eb009a719ebee1504c451622165e40c9ded3c16065e567e3b5
• Download URL:
  https://stacks.cdc.gov/view/cdc/80582/cdc_80582_DS1.pdf
• File Type:
  [PDF - 1.84 MB ]