一、研究新知
Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan
Fumiaki Obata, Masayuki Miura. NATURE COMMUNICATIONS. August 2015, Volume 6:8332.
Methionine restriction extends the lifespan of various model organisms.
Limiting S-adenosylmethionine (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.
原文連結：
Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan