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Longevity regulation by NMD-mediated mRNA quality control
Heehwa G. Son1, Seung-Jae V. Lee1,*
1Department of Life Sciences and 2School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 37673, Pohang, Gyeongbuk, South Korea
Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remained largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for long lifespan in C. elegans. We further demonstrate that animals with reduced insulin/IGF-1 signaling (IIS), a representative longevity model, display increased NMD activity. We propose that up-regulation of NMD plays crucial roles in longevity conferred by reduced IIS via enhancing mRNA quality control. As both IIS and NMD pathways are evolutionarily conserved, mammals including humans may be equipped with similar RNA quality control systems to achieve longevity.
Abstract, Accepted Manuscript [Submitted on March 14, 2017, Accepted on March 14, 2017]
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