Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56 mg/dL) levels compared to CF. Adiponectin, which increases with MR, did not change in GS after 12 w on diet. We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde.
Clever, a methionine restriction mimetic. This would be much easier to implement than restricting methionine (methinks). The rats did get a hefty dose of glycine, up to 12% of diet. Seems to me that lower amounts (grams) might be effective in humans.
In another paper with the same lead author (Orentreich), methionine restriction caused a large rise in glutathione levels, which I strongly suspect has a role in causation of longer lifespan.
PS: I’d already had this post scheduled a couple days when I got a comment from a blogger whose blog was previously unknown to me, Valtsu, and he has a comprehensive post on glycine.