Methionine restriction extends the lifespan of various model organisms. LimitingS-adenosyl-methionine (SAM) synthesis, the first metabolic reaction of dietary methionine, extends longevity in Caenorhabditis elegansbut accelerates pathology in mammals.
Scientists in the journal nature Communications show that, as an alternative to inhibiting SAM synthesis, enhancement of SAM catabolism by glycineN-methyltransferase (Gnmt) extends the lifespan inDrosophila.
Gnmt strongly buffers systemic SAM levels by producing sarcosine in either high-methionine or low-samsconditions.
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 ofgnmtsuppresses 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 inDrosophila.
This study suggests that regulation of SAM levels by Gnmt is a key component of lifespan extension.