The Interventions Testing Program Finds Glycine Supplementation has a Tiny Effect on Mouse Life Span
The NIA Interventions Testing Program (ITP) is a very conservative organization. The organizers take compounds that cannot possibly do more than slightly slow aging, largely those that upregulate stress response mechanisms in a similar way to calorie restriction, and rigorously test them in large mouse studies. The results are of the best quality, and tend to demonstrate that most earlier, less rigorous studies overestimated the effects of compounds on life span. This is an expensive business, but I would say one of dubious practical value.
The practice of calorie restriction shows us the likely bounds of the possible when it comes to upregulating stress responses in humans. It is not the road to large increases in human life span; calorie restriction, while improving health noticeable, doesn't add more than a few years to life span in our species. This is despite extending mouse life span by up to 40%. Upregulation of stress responses has evolved to have a much larger effect on life span in short-lived species. So when we see results in mice on the order of 5% extension of life span in the ITP study noted here, one can expect it to have absolutely no detectable result at all in humans.
The NIA Interventions Testing Program (ITP) has to date reported on four drugs with consistent major effects on mouse lifespan in one or both sexes and found evidence for significant but less dramatic effect of four other drugs. Rapamycin, started at 9 months of age, was found to increase median lifespan by as much as 26% in females and 23% in males. Acarbose can lead to an increase of 22% in median lifespan in male mice, and to a significant, but smaller, 5% increase in female mice. A third drug, 17-α-estradiol (17aE2), a nonfeminizing congener of the well-known estrogen 17-β-estradiol, increases lifespan of male mice by 19%. Lastly, NDGA (nordihydroguaiaretic acid) has been shown to increase lifespan of male mice only, with an increase of 12% in median lifespan. Of the other agents tested so far by the ITP, four (methylene blue, aspirin, Protandim, and green tea extract [GTE]) provided some evidence for possible health benefits.
Diets low in the amino acid methionine have been shown to extend median and maximum lifespan in rats. Glycine plays a special role in methionine metabolism, serving as the only acceptor for methyl groups, through action of glycine-N-methyl transferase (GNMT), the key enzyme in the only pathway for methionine clearance in mammals. Methionine toxicity can be blocked by dietary glycine, consistent with the notion that GNMT is the principal effector of methionine clearance, at least at toxic levels. These data suggest that excess dietary glycine might depress methionine levels and thus mimic some of the benefits of a low methionine diet.
We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%-6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males and females. Pooling across sex, glycine increased lifespan at each of the three independent test sites. Glycine-supplemented females were lighter than controls, but there was no effect on weight in males.