Bacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling

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dc.contributor.authorMin-Gi Shin-
dc.contributor.authorJae-Woong Lee-
dc.contributor.authorJun-Seok Han-
dc.contributor.authorBora Lee-
dc.contributor.authorJin Hyuck Jeong-
dc.contributor.authorSo Hyun Park-
dc.contributor.authorJong Hwan Kim-
dc.contributor.authorS Jang-
dc.contributor.authorMooncheol Park-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorS Kim-
dc.contributor.authorYong Ryoul Yang-
dc.contributor.authorJ Y Kim-
dc.contributor.authorK L Hoe-
dc.contributor.authorC Park-
dc.contributor.authorKwang-Pyo Lee-
dc.contributor.authorKi-Sun Kwon-
dc.contributor.authorEun Soo Kwon-
dc.date.accessioned2020-09-24T03:55:25Z-
dc.date.available2020-09-24T03:55:25Z-
dc.date.issued2020-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/22770-
dc.description.abstractGut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.-
dc.publisherNatl Acad Sciences-
dc.titleBacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling-
dc.title.alternativeBacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling-
dc.typeArticle-
dc.citation.titleProceedings of National Academy of Sciences of United States of America-
dc.citation.number29-
dc.citation.endPage17150-
dc.citation.startPage17142-
dc.citation.volume117-
dc.contributor.affiliatedAuthorMin-Gi Shin-
dc.contributor.affiliatedAuthorJae-Woong Lee-
dc.contributor.affiliatedAuthorJun-Seok Han-
dc.contributor.affiliatedAuthorBora Lee-
dc.contributor.affiliatedAuthorJin Hyuck Jeong-
dc.contributor.affiliatedAuthorSo Hyun Park-
dc.contributor.affiliatedAuthorJong Hwan Kim-
dc.contributor.affiliatedAuthorMooncheol Park-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorYong Ryoul Yang-
dc.contributor.affiliatedAuthorKwang-Pyo Lee-
dc.contributor.affiliatedAuthorKi-Sun Kwon-
dc.contributor.affiliatedAuthorEun Soo Kwon-
dc.contributor.alternativeName신민기-
dc.contributor.alternativeName이재웅-
dc.contributor.alternativeName한준석-
dc.contributor.alternativeName이보라-
dc.contributor.alternativeName정진혁-
dc.contributor.alternativeName박소현-
dc.contributor.alternativeName김종환-
dc.contributor.alternativeName장수미-
dc.contributor.alternativeName박문철-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName김석호-
dc.contributor.alternativeName양용렬-
dc.contributor.alternativeName김정윤-
dc.contributor.alternativeName허광래-
dc.contributor.alternativeName박찬규-
dc.contributor.alternativeName이광표-
dc.contributor.alternativeName권기선-
dc.contributor.alternativeName권은수-
dc.identifier.bibliographicCitationProceedings of National Academy of Sciences of United States of America, vol. 117, no. 29, pp. 17142-17150-
dc.identifier.doi10.1073/pnas.1915719117-
dc.subject.keywordgut microbe-
dc.subject.keywordlongevity-
dc.subject.keywordmethylglyoxal-
dc.subject.keywordDAF-16-
dc.subject.localgut microbe-
dc.subject.localgut microbes-
dc.subject.locallongevity-
dc.subject.localLongevity-
dc.subject.localmethylglyoxal-
dc.subject.localMethylglyoxal-
dc.subject.localDAF-16-
dc.description.journalClassY-
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Aging Convergence Research Center > 1. Journal Articles
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