Going all the way back to the 1930s, researchers have demonstrated that limiting the amount of food eaten by their lab animals, from fruit flies to rodents to, more recently, large mammals, reliably extended their lifespans. Fair to say that calorie restriction has provided the foundation for what we now call longevity medicine. And, however the hunt for game-changing longevity drugs plays out, it’s worth noting that basic nutrients can play an important role in helping to determine how long we get to live. One of the most intriguing of these nutrients is glycine.
Glycine is one of twenty amino acids which constitute the building blocks for the proteins our body makes. It’s a key constituent of collagen (raw material for connective tissue, bone, skin, nails), the most abundant protein in the body. While it’s regarded as a “non-essential” amino acid – our bodies can synthesize it so we don’t have to consume it in our diet – the available evidence from animal and human research suggests that the more glycine in our systems the better. Certain foods are glycine-rich, like tough, gristly meat (lots of collagen in the animal connective tissue), but much higher concentrations are available in supplement form.
The theoretical benefits of supplemental glycine return us to that pioneering longevity research on caloric restriction. While CR extends the lives of lab animals by sharpening their metabolism, keeping a lid on insulin levels, for example, it’s always been debatable how useful it might be for humans. Being too thin in older age sets us up for frailty, no matter how optimal our metabolic numbers, and going through life somewhat hungry is, for most of us, neither practicable nor fun. But higher glycine levels seem to capture one important element of the CR longevity boost, without the need to cut calories.
The biochemistry is not uncomplicated but here’s a somewhat simplified version. Adequate levels of glycine in the body keep the level of another amino acid, methionine, found in meat (in the muscle, not the connective tissue), eggs and seafood from rising too high. Unlike glycine, methionine is an essential amino acid – our survival depends on getting some in our diet – but too much of it is associated with poor health outcomes, especially a sluggish metabolism that generates too much toxic waste. (High levels also correlate with elevated levels of homocysteine, an amino acid break-down product associated with poor cardiovascular health.)
The animal research suggests that a specific enzyme, GNMT (glycine N-methyltransferase), strips off a piece of the methionine molecule, a methyl group to be precise, and transfers it to the glycine molecule to create the amino acid derivative sarcosine. That’s a good thing. Sarcosine promotes autophagy, our cellular trash collection system. Boosting sarcosine production helps counter its age-related decline, which over time, makes autophagy a less efficient process—a key hallmark of aging Although the biochemical details are still being worked out, multiple epigenetic clocks use genes related to glycine metabolism to predict epigenetic age.
So, that’s a nice mechanistic theory but do we have evidence that adding supplemental glycine to the diet actually provides measurable benefit? We do. A raft of animal studies – from flies to worms to rodents – have demonstrated that glycine extends lifespan, depending on the species and the study, anywhere from nearly 4% to 28%. Unsurprisingly, health markers improve as well, particularly those measuring metabolic health. While equivalent human longevity studies would be virtually impossible to conduct, we do have short-term clinical research showing glycine supplementation lowering pro-inflammatory cytokines and hemoglobin A1c in type 2 diabetics and systolic blood pressure in patients with metabolic syndrome.
Glycine is something like those multi-pronged kitchen implements sold on late-night cable – it’s serviceable in any number of different ways. Higher levels replenish glutathione, a powerful antioxidant that helps the body resist oxidative stress, ditto, creatine, a molecule the body uses to power short, intense muscular contraction. In the brain, it functions like a neurotransmitter (working through the NDMA pathway). Accordingly, researchers have begun investigating glycine supplementation as a way to push back against age-related declines in learning and memory, and it has shown some promise as a therapy for schizophrenia.
The entire research track record has been analyzed in a 2023 review published in Aging Research Reviews. The two authors can’t claim to be completely disinterested -- they work for longevity eminence David Sinclair’s Tally Health, which produces a supplement containing, among the other ingredients, a gram of glycine. But I’m impressed by their reading of the scientific literature. I’m currently taking magnesium glycinate (magnesium combined with glycine) at a relatively modest dose at night for its sleep inducing effects and potential memory and learning benefits. But a growing number of people in the longevity world are supplementing on the order of 3-5 grams a day. Given that I’ve seen no evidence of side-effects at this admittedly generous dose, I’m considering giving it a try myself.
Adiv A. Johnson, Trinna L. Cuellar. Glycine and aging: Evidence and mechanisms. Aging Research Reviews. Volume 87, June 2023. doi.org/10.1016/j.arr.2023.101922.
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