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1000 Titel
  • Branched-chain amino acid catabolism is a conserved regulator of physiological ageing
1000 Autor/in
  1. Mansfeld, Johannes |
  2. Urban, Nadine |
  3. Priebe, Steffen |
  4. Frahm, Christiane |
  5. Hartmann, Nils |
  6. Gebauer, Juliane |
  7. Ravichandran, Meenakshi |
  8. Dommaschk, Anne |
  9. Schmeisser, Sebastian |
  10. Kuhlow, Doreen |
  11. Bremer-Streck, Sibylle |
  12. Hemmerich, Peter |
  13. Kiehntopf, Michael |
  14. Zamboni, Nicola |
  15. Guthke, Reinhard |
  16. Kaleta, Christoph |
  17. Platzer, Matthias |
  18. Sühnel, Jürgen |
  19. Witte, Otto W. |
  20. Zarse, Kim |
  21. Ristow, Michael |
  22. Groth, Marco |
  23. Englert, Christoph |
1000 Erscheinungsjahr 2015
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-12-01
1000 Erschienen in
1000 Quellenangabe
  • 6:10043
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • http://dx.doi.org/10.1038/ncomms10043 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686672/ |
1000 Ergänzendes Material
  • http://www.nature.com/articles/ncomms10043#additional-information |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.
1000 Sacherschließung
lokal Cell signalling
lokal Medical research
lokal Ageing
lokal Metabolism
1000 Fachgruppe
  1. Medizin |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/TWFuc2ZlbGQsIEpvaGFubmVz|https://frl.publisso.de/adhoc/creator/VXJiYW4sIE5hZGluZQ==|https://frl.publisso.de/adhoc/creator/UHJpZWJlLCBTdGVmZmVu|https://frl.publisso.de/adhoc/creator/RnJhaG0sIENocmlzdGlhbmU=|https://frl.publisso.de/adhoc/creator/SGFydG1hbm4sIE5pbHM=|https://frl.publisso.de/adhoc/creator/R2ViYXVlciwgSnVsaWFuZQ==|https://frl.publisso.de/adhoc/creator/UmF2aWNoYW5kcmFuLCBNZWVuYWtzaGk=|https://frl.publisso.de/adhoc/creator/RG9tbWFzY2hrLCBBbm5l|https://frl.publisso.de/adhoc/creator/U2NobWVpc3NlciwgU2ViYXN0aWFu|https://frl.publisso.de/adhoc/creator/S3VobG93LCBEb3JlZW4=|https://frl.publisso.de/adhoc/creator/QnJlbWVyLVN0cmVjaywgU2lieWxsZQ==|https://frl.publisso.de/adhoc/creator/SGVtbWVyaWNoLCBQZXRlcg==|https://frl.publisso.de/adhoc/creator/S2llaG50b3BmLCBNaWNoYWVs|https://frl.publisso.de/adhoc/creator/WmFtYm9uaSwgTmljb2xh|https://frl.publisso.de/adhoc/creator/R3V0aGtlLCBSZWluaGFyZA==|https://frl.publisso.de/adhoc/creator/S2FsZXRhLCBDaHJpc3RvcGg=|https://frl.publisso.de/adhoc/creator/UGxhdHplciwgTWF0dGhpYXM=|https://frl.publisso.de/adhoc/creator/U8O8aG5lbCwgSsO8cmdlbg==|https://frl.publisso.de/adhoc/creator/V2l0dGUsIE90dG8gVy4=|https://frl.publisso.de/adhoc/creator/WmFyc2UsIEtpbQ==|https://frl.publisso.de/adhoc/creator/UmlzdG93LCBNaWNoYWVs|http://orcid.org/0000-0002-9199-8990|http://orcid.org/0000-0003-3284-8359
1000 Förderer
  1. German Ministry for Education and Research (Bundesministerium für Bildung und Forschung/BMBF) |
  2. German Research Association (Deutsche Forschungsgemeinschaft, DFG) |
  3. Swiss National Science Foundation (Schweizerischer Nationalfonds) |
1000 Fördernummer
  1. 0315581
  2. -
  3. SNF 31003A_156031
1000 Förderprogramm
  1. -
  2. Research Training Group 1715 Molecular Signatures of Adaptive Stress Responses, Jena, Germany
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Ministry for Education and Research (Bundesministerium für Bildung und Forschung/BMBF) |
    1000 Förderprogramm -
    1000 Fördernummer 0315581
  2. 1000 joinedFunding-child
    1000 Förderer German Research Association (Deutsche Forschungsgemeinschaft, DFG) |
    1000 Förderprogramm Research Training Group 1715 Molecular Signatures of Adaptive Stress Responses, Jena, Germany
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Swiss National Science Foundation (Schweizerischer Nationalfonds) |
    1000 Förderprogramm -
    1000 Fördernummer SNF 31003A_156031
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404724.rdf
1000 Erstellt am 2017-09-27T13:21:52.411+0200
1000 Erstellt von 122
1000 beschreibt frl:6404724
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Mon May 07 11:18:22 CEST 2018
1000 Objekt bearb. Mon May 07 11:18:21 CEST 2018
1000 Vgl. frl:6404724
1000 Oai Id
  1. oai:frl.publisso.de:frl:6404724 |
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