Haeri Choi , Sung Chun Cho , Young Wan Ha , Billie Ocampo , Shirley Park , Shiwen Chen , Christopher F. Bennett , Jeehae Han , Ryan Rossner , Jong-Sun Kang , Yun-ll Lee , Sang Chul Park , Matt Kaeberlein
{"title":"DDS promotes longevity through a microbiome-mediated starvation signal","authors":"Haeri Choi , Sung Chun Cho , Young Wan Ha , Billie Ocampo , Shirley Park , Shiwen Chen , Christopher F. Bennett , Jeehae Han , Ryan Rossner , Jong-Sun Kang , Yun-ll Lee , Sang Chul Park , Matt Kaeberlein","doi":"10.1016/j.tma.2019.07.001","DOIUrl":null,"url":null,"abstract":"<div><p>The antibiotic diaminodiphenyl sulfone (DDS) is used in combination with other antibiotics as a first line treatment for leprosy. DDS has been previously reported to extend lifespan in <em>Caenorhabditis elegans</em> through inhibition of pyruvate kinase and decreased mitochondrial function. Here we report an alternative mechanism of action by which DDS promotes longevity in <em>C. elegans</em> by reducing folate production by the microbiome. This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"3 ","pages":"Pages 64-69"},"PeriodicalIF":0.0000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2019.07.001","citationCount":"8","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Medicine of Aging","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468501119300045","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 8
Abstract
The antibiotic diaminodiphenyl sulfone (DDS) is used in combination with other antibiotics as a first line treatment for leprosy. DDS has been previously reported to extend lifespan in Caenorhabditis elegans through inhibition of pyruvate kinase and decreased mitochondrial function. Here we report an alternative mechanism of action by which DDS promotes longevity in C. elegans by reducing folate production by the microbiome. This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.