title: Aging is associated with hypermethylation of autophagy genes in macrophages.
abstract: Autophagy is a biological process characterized by self-digestion and involves induction of autophagosome formation, leading to degradation of autophagic cargo. Aging is associated with the reduction of autophagy activity leading to neurodegenerative disorders, chronic inflammation, and susceptibility to infection; however, the underlying mechanism is unclear. DNA methylation by DNA methyltransferases reduces the expression of corresponding genes. Since macrophages are major players in inflammation and defense against infection we determined the differences in methylation of autophagy genes in macrophages derived from young and aged mice. We found that promoter regions of Atg5 and LC3B are hypermethylated in macrophages from aged mice and this is accompanied by low gene expression. Treatment of aged mice and their derived macrophages with methyltransferase inhibitor (2)-epigallocatechin-3-gallate (EGCG) or specific DNA methyltransferase 2 (DNMT2) siRNA restored the expression of Atg5 and LC3 in vivo and in vitro. Our study builds a foundation for the development of novel therapeutics aimed to improve autophagy in the elderly population and suggests a role for DNMT2 in DNA methylation activities.
authors.affiliation: a Department of Molecular Biology , Genetic Engineering and Biotechnology Research Institute, University of Sadat City , Sadat City , Egypt.
authors.forename: Hany
authors.initials: H
authors.lastname: Khalil
authors.affiliation: b Department of Microbial Infection and Immunity , Center for Microbial Interface Biology, The Ohio State University , Columbus , OH.|c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Mia
authors.initials: M
authors.lastname: Tazi
authors.affiliation: b Department of Microbial Infection and Immunity , Center for Microbial Interface Biology, The Ohio State University , Columbus , OH.|c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Kyle
authors.initials: K
authors.lastname: Caution
authors.affiliation: b Department of Microbial Infection and Immunity , Center for Microbial Interface Biology, The Ohio State University , Columbus , OH.|c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Amr
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: b Department of Microbial Infection and Immunity , Center for Microbial Interface Biology, The Ohio State University , Columbus , OH.|c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Apurva
authors.initials: A
authors.lastname: Kanneganti
authors.affiliation: d The Research Institute at Nationwide Children's Hospital, The Ohio State University , Columbus , OH.
authors.forename: Kaivon
authors.initials: K
authors.lastname: Assani
authors.affiliation: d The Research Institute at Nationwide Children's Hospital, The Ohio State University , Columbus , OH.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kopp
authors.affiliation: c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Clay
authors.initials: C
authors.lastname: Marsh
authors.affiliation: c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Duaa
authors.initials: D
authors.lastname: Dakhlallah
authors.affiliation: b Department of Microbial Infection and Immunity , Center for Microbial Interface Biology, The Ohio State University , Columbus , OH.|c The Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH.
authors.forename: Amal O
authors.initials: AO
authors.lastname: Amer
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000235:genetics*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D004791:Enzyme Inhibitors; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D002392:Catechin; C045651:epigallocatechin gallate; C491786:Dnmt2 protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: Aging; DNA methylation; EGCG; autophagy; macrophages