Fight Aging!

Supplementation with the non-essential amino acid glycine has been shown to modestly slow aging in short-lived laboratory species. In today's open access review paper, researchers note glycine supplementation as essentially a calorie restriction mimetic approach that works primarily through effects on methionine sensing. Much of the broadly beneficial metabolic response to lowered calorie intake occurs because cells react to low levels of the essential amino acid methionine in ways that increase efficiency of protein production and reuse of materials. For example, this increases the activity of cellular housekeeping activities such as autophagy. More housekeeping means better functioning cells and tissues, and kept up over the long term this has the desirable outcome of lengthening healthy life span.

Unfortunately we know that while short-term benefits to health metrics achieved via this sort of approach are much the same in mice versus humans, and thus some form of calorie restriction seems a sensible health practice, long-term effects on life span are much smaller in long-lived species. It remains to be understood as to exactly why this is the case, but from an evolutionary perspective one might argue that many of the metabolic changes taking place in response to calorie restriction in a short-lived mammals are already permanently turned on in a long-lived mammal in order to enable individuals of that species to be long-lived in the first place.

Glycine and aging: Evidence and mechanisms

The restriction of calories, branched-chain amino acids, and methionine have all been shown to extend lifespan in model organisms. Recently, glycine was shown to significantly boost longevity in genetically heterogenous mice. This simple amino acid similarly extends lifespan in rats and improves health in mammalian models of age-related disease. While compelling data indicate that glycine is a pro-longevity molecule, divergent mechanisms may underlie its effects on aging.

Glycine is abundant in collagen, a building block for glutathione, a precursor to creatine, and an acceptor for the enzyme Glycine N-methyltransferase (GNMT). A review of the literature strongly implicates GNMT, which clears methionine from the body by taking a methyl group from S-adenosyl-L-methionine and methylating glycine to form sarcosine. In flies, Gnmt is required for reduced insulin/insulin-like growth factor 1 signaling and caloric restriction to fully extend lifespan. The geroprotector spermidine requires Gnmt to upregulate autophagy genes and boost longevity. Moreover, the overexpression of Gnmt is sufficient to extend lifespan and reduce methionine levels. Sarcosine, also known as methylglycine, declines with age in multiple species and is capable of inducing autophagy both in vitro and in vivo.

Taken all together, existing evidence suggests that glycine prolongs life by mimicking methionine restriction and activating autophagy. In this review, we provide a detailed overview of the current evidence that glycine is a pro-longevity molecule, a so-called geroprotector. By exploring and synthesizing available data, we also offer a tentative mechanistic explanation for how this simple amino acid may target biological aging and prolong life.