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Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4458-67. doi: 10.1073/pnas.1411199111. Epub 2014 Oct 6.

Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans.

Author information

1
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;
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853;
3
Theragnosis Research Center BRI, Korea Institute of Science and Technology, Seoul 136-791, South Korea;
4
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115; and.
5
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.
6
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.

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.

KEYWORDS:

C. elegans; aging; immunity; mitochondria; reactive oxygen species

PMID:
25288734
PMCID:
PMC4210294
DOI:
10.1073/pnas.1411199111
[Indexed for MEDLINE]
Free PMC Article

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