Abstract
Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation. Moreover, the effect of Indy/CeNAC2 knockdown in C. elegans with inactivating variants of AMPK (TG38) was studied. Knockdown of Indy/CeNAC2 increased life span by 22±3 % compared to control siRNA treated C. elegans, together with a decrease in whole body fat content by ~50%. Indy/CeNAC2 reduction also increased the activation of the intracellular energy sensor AMPK/aak2. In worms without functional AMPK/aak2, life span was not extended when Indy/CeNAC2 was reduced. Inhibition of glycolysis with deoxyglucose, an intervention known to increase AMPK/aak2 activity and life span, did not promote longevity when Indy/CeNA...Continue Reading
References
Dec 2, 1993·Nature·C KenyonR Tabtiang
Dec 16, 2000·Science·B RoginaS L Helfand
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Felix KnaufStephen L Helfand
Jun 27, 2003·The Biochemical Journal·Katsuhisa InoueVadivel Ganapathy
Dec 18, 2003·The Biochemical Journal·You-Jun FeiVadivel Ganapathy
Dec 3, 2004·Genes & Development·Javier ApfeldRory Curtis
Oct 8, 2005·Pflügers Archiv : European journal of physiology·Ana M Pajor
Feb 6, 2007·Cell Metabolism·Richard M ReznickGerald I Shulman
Jun 19, 2007·PLoS Genetics·Janne M ToivonenLinda Partridge
Oct 3, 2007·Cell Metabolism·Tim J SchulzMichael Ristow
Dec 25, 2007·Experimental Biology and Medicine·Elmus G Beale
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nicola NerettiStephen L Helfand
May 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Janne M ToivonenLinda Partridge
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Pei-Yu WangStephen L Helfand
Aug 2, 2011·Cell Metabolism·Andreas L BirkenfeldGerald I Shulman
Sep 23, 2011·Aging·Gerald I Shulman, Stephen L Helfand
Nov 8, 2011·Investigative Ophthalmology & Visual Science·Shunsuke KubotaKazuo Tsubota
Oct 23, 2012·Nature·Romina MancussoDa-Neng Wang
Nov 14, 2013·Diabetes·Frank Neuschäfer-RubeAndreas L Birkenfeld
Feb 13, 2014·Aging·Chen-Tseh ZhuStephen L Helfand
Jan 1, 2013·Computational and Structural Biotechnology Journal·Diana M Willmes, Andreas L Birkenfeld
Apr 15, 2014·Cell Metabolism·Kristopher BurkewitzWilliam B Mair
May 16, 2014·Aging·Ryan P Rogers, Blanka Rogina
May 23, 2014·Nature·Anila K MadirajuGerald I Shulman
Citations
Jun 10, 2017·Frontiers in Genetics·Blanka Rogina
Jul 29, 2018·Scientific Reports·Stefan SelchJörg König
Nov 3, 2016·Molecular Pharmacology·Ana M PajorDerek M Erion
Dec 29, 2019·Pharmacological Reviews·Tina SchumannAndreas L Birkenfeld
Jun 5, 2016·Biogerontology·Antero SalminenAnu Kauppinen
Dec 10, 2015·Aging·Dominik H PestaAndreas L Birkenfeld
Mar 2, 2016·Aging·Diana M WillmesAndreas L Birkenfeld
Mar 17, 2018·BioMed Research International·Wan-Angkan PoolsriPiyarat Srisawang
Jan 31, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christian von LoeffelholzAndreas L Birkenfeld
Jun 15, 2017·Aging·James A McCubreyMelchiorre Cervello
Jan 26, 2021·JCI Insight·Diana M WillmesAndreas L Birkenfeld
Jul 8, 2020·Toxicology and Applied Pharmacology·Tao HuHongbing Wang
Oct 30, 2021·PLoS Genetics·Jiwon JeongChunghun Lim
Nov 2, 2021·Aging Cell·Shou-Zen FanPei-Yu Wang
Dec 1, 2021·Rejuvenation Research·Andrew R Mendelsohn, James Larrick