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

Title
Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans
Authors
Ara B. HwangEun-A RyuMurat ArtanHsin-Wen ChangKabir Mohammad Humayun남현준이동엽양재승김상욱William B Mair이철주Siu Sylvia Lee이승재
Keywords
aging; mitochondria; immunity; reactive oxygen species; C. elegans
Issue Date
2014-10
Publisher
Proceedings of the National Academy of Sciences of the United States of America
Citation
VOL 111, NO 42, E4458-E4467
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.
URI
http://pubs.kist.re.kr/handle/201004/48802
ISSN
00278424
Appears in Collections:
KIST Publication > Article
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