Reference - Detail
| RRC ID | 83418 |
|---|---|
| Author | Obata F, Miura M. |
| Title | Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan. |
| Journal | Nat Commun |
| Abstract |
Methionine restriction extends the lifespan of various model organisms. Limiting S-adenosyl-methionine (SAM) synthesis, the first metabolic reaction of dietary methionine, extends longevity in Caenorhabditis elegans but accelerates pathology in mammals. Here, we show that, as an alternative to inhibiting SAM synthesis, enhancement of SAM catabolism by glycine N-methyltransferase (Gnmt) extends the lifespan in Drosophila. Gnmt strongly buffers systemic SAM levels by producing sarcosine in either high-methionine or low-sams conditions. During ageing, systemic SAM levels in flies are increased. Gnmt is transcriptionally induced in a dFoxO-dependent manner; however, this is insufficient to suppress SAM elevation completely in old flies. Overexpression of gnmt suppresses this age-dependent SAM increase and extends longevity. Pro-longevity regimens, such as dietary restriction or reduced insulin signalling, attenuate the age-dependent SAM increase, and rely at least partially on Gnmt function to exert their lifespan-extending effect in Drosophila. Our study suggests that regulation of SAM levels by Gnmt is a key component of lifespan extension. |
| Volume | 6 |
| Pages | 8332 |
| Published | 2015-9-18 |
| DOI | 10.1038/ncomms9332 |
| PII | ncomms9332 |
| PMID | 26383889 |
| PMC | PMC4595730 |
| MeSH | Aging / metabolism* Animals Animals, Genetically Modified Blotting, Western Caloric Restriction Chromatography, Liquid Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Gene Knockdown Techniques Glycine N-Methyltransferase / genetics* Glycine N-Methyltransferase / metabolism Insulin / metabolism Longevity* Methionine Adenosyltransferase / genetics* Methionine Adenosyltransferase / metabolism Real-Time Polymerase Chain Reaction S-Adenosylmethionine / metabolism* Sarcosine / metabolism Tandem Mass Spectrometry |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 36 |
| Altmetric score changes over past 6months | 0.7 |
| Resource | |
| Drosophila | DGRC#119578 DGRC#119579 DGRC#119581 DGRC#119582 DGRC#119583 DGRC#119584 DGRC#119585 DGRC#119586 DGRC#119587 DGRC#119588 |