Title |
Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide
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Published in |
Nature Chemical Biology, September 2013
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DOI | 10.1038/nchembio.1352 |
Pubmed ID | |
Authors |
Kathrin Schmeisser, Johannes Mansfeld, Doreen Kuhlow, Sandra Weimer, Steffen Priebe, Ines Heiland, Marc Birringer, Marco Groth, Alexandra Segref, Yariv Kanfi, Nathan L Price, Sebastian Schmeisser, Stefan Schuster, Andreas F H Pfeiffer, Reinhard Guthke, Matthias Platzer, Thorsten Hoppe, Haim Y Cohen, Kim Zarse, David A Sinclair, Michael Ristow |
Abstract |
Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan. In contrast with recent observations, here we find that overexpression of sir-2.1, the ortholog of mammalian SirT1, does extend Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir-2.1. We identify a previously unknown C. elegans nicotinamide-N-methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM. Disruption and overexpression of anmt-1 have opposing effects on lifespan independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated lifespan extension. MNA serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic reactive oxygen species signal to promote C. elegans longevity. Taken together, sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 23% |
United Kingdom | 2 | 15% |
Japan | 1 | 8% |
Germany | 1 | 8% |
Unknown | 6 | 46% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 10 | 77% |
Scientists | 2 | 15% |
Practitioners (doctors, other healthcare professionals) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
Belgium | 3 | 1% |
France | 2 | <1% |
Norway | 1 | <1% |
United Kingdom | 1 | <1% |
Japan | 1 | <1% |
Estonia | 1 | <1% |
Unknown | 267 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 65 | 23% |
Student > Ph. D. Student | 61 | 22% |
Student > Master | 31 | 11% |
Student > Bachelor | 23 | 8% |
Professor | 14 | 5% |
Other | 50 | 18% |
Unknown | 35 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 86 | 31% |
Biochemistry, Genetics and Molecular Biology | 55 | 20% |
Medicine and Dentistry | 33 | 12% |
Chemistry | 24 | 9% |
Neuroscience | 7 | 3% |
Other | 22 | 8% |
Unknown | 52 | 19% |