title: Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans.
abstract: Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS.
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Ara B
authors.initials: AB
authors.lastname: Hwang
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Ryu
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Murat
authors.initials: M
authors.lastname: Artan
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853;
authors.forename: Hsin-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Theragnosis Research Center BRI, Korea Institute of Science and Technology, Seoul 136-791, South Korea;
authors.forename: Mohammad Humayun
authors.initials: MH
authors.lastname: Kabir
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115; and.
authors.forename: William B
authors.initials: WB
authors.lastname: Mair
authors.affiliation: Theragnosis Research Center BRI, Korea Institute of Science and Technology, Seoul 136-791, South Korea; Department of Biological Chemistry, University of Science and Technology, Daejeon 305-350, South Korea.
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853;
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Division of Information Technology Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea; seungjaelee@postech.ac.kr.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D019069:Cell Respiration; D025461:Feedback, Physiological; D006706:Homeostasis; D007501:Iron / Q000737:chemistry; D008136:Longevity / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D010269:Paraquat / Q000737:chemistry; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C541178:HIF-1 protein, C elegans; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D007501:Iron; D055372:AMP-Activated Protein Kinases; D010269:Paraquat
keywords: C. elegans; aging; immunity; mitochondria; reactive oxygen species