Branched-chain amino acid catabolism is a conserved regulator of physiological ageing
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785206 | ||
| 005 | 20190713030951.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2015 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000108449 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms10043 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/108449 | ||
| 245 | 0 | 0 | |a Branched-chain amino acid catabolism is a conserved regulator of physiological ageing |h [Elektronische Daten] |c [Johannes Mansfeld, Nadine Urban, Steffen Priebe, Marco Groth, Christiane Frahm, Nils Hartmann, Juliane Gebauer, Meenakshi Ravichandran, Anne Dommaschk, Sebastian Schmeisser, Doreen Kuhlow, Shamci Monajembashi, Sibylle Bremer-Streck, Peter Hemmerich, Michael Kiehntopf, Nicola; id_orcid 0000-0003-1271-1021 Zamboni, Christoph Englert, Reinhard Guthke, Christoph Kaleta, Matthias Platzer, Jürgen Sühnel, Otto W. Witte, Kim Zarse, Michael; id_orcid 0000-0003-2109-2453 Ristow] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Mansfeld |D Johannes |e joint author | |
| 700 | 1 | |a Urban |D Nadine |e joint author | |
| 700 | 1 | |a Priebe |D Steffen |e joint author | |
| 700 | 1 | |a Groth |D Marco |e joint author | |
| 700 | 1 | |a Frahm |D Christiane |e joint author | |
| 700 | 1 | |a Hartmann |D Nils |e joint author | |
| 700 | 1 | |a Gebauer |D Juliane |e joint author | |
| 700 | 1 | |a Ravichandran |D Meenakshi |e joint author | |
| 700 | 1 | |a Dommaschk |D Anne |e joint author | |
| 700 | 1 | |a Schmeisser |D Sebastian |e joint author | |
| 700 | 1 | |a Kuhlow |D Doreen |e joint author | |
| 700 | 1 | |a Monajembashi |D Shamci |e joint author | |
| 700 | 1 | |a Bremer-Streck |D Sibylle |e joint author | |
| 700 | 1 | |a Hemmerich |D Peter |e joint author | |
| 700 | 1 | |a Kiehntopf |D Michael |e joint author | |
| 700 | 1 | |a Zamboni |D Nicola; id_orcid 0000-0003-1271-1021 |e joint author | |
| 700 | 1 | |a Englert |D Christoph |e joint author | |
| 700 | 1 | |a Guthke |D Reinhard |e joint author | |
| 700 | 1 | |a Kaleta |D Christoph |e joint author | |
| 700 | 1 | |a Platzer |D Matthias |e joint author | |
| 700 | 1 | |a Sühnel |D Jürgen |e joint author | |
| 700 | 1 | |a Witte |D Otto W. |e joint author | |
| 700 | 1 | |a Zarse |D Kim |e joint author | |
| 700 | 1 | |a Ristow |D Michael; id_orcid 0000-0003-2109-2453 |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 6, p. 10043 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/108449 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/108449 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Mansfeld |D Johannes |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Urban |D Nadine |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Priebe |D Steffen |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Groth |D Marco |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Frahm |D Christiane |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hartmann |D Nils |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Gebauer |D Juliane |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Ravichandran |D Meenakshi |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Dommaschk |D Anne |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schmeisser |D Sebastian |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Kuhlow |D Doreen |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Monajembashi |D Shamci |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Bremer-Streck |D Sibylle |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hemmerich |D Peter |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Kiehntopf |D Michael |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Zamboni |D Nicola; id_orcid 0000-0003-1271-1021 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Englert |D Christoph |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Guthke |D Reinhard |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Kaleta |D Christoph |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Platzer |D Matthias |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Sühnel |D Jürgen |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Witte |D Otto W. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Zarse |D Kim |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Ristow |D Michael; id_orcid 0000-0003-2109-2453 |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 6, p. 10043 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||