I find it interesting that Glycine promotes longevity and protects against sarcopenia by activating MTORC1. Rapamycin seems to neutralize some of the effects of Glycine, although Rapamycin seems to overrule Glycine. Yet, when Rapamycin levels wane, Glycine’s benefits can kick in. Seems that alternating between the two (or just constantly dosing Glycine) would have a beneficial effect. Or better yet, Glycine + NAC. Based on this data, I will stop taking NAC on the immediate days after dosing with Rapamycin.
Thoughts?
The non-essential amino acid glycine is often considered biologically neutral, and not required for the regulation of protein synthesis under normal healthy conditions. However, reduced intracellular levels of glycine have been reported in older individuals (1) and in mouse models of diabetes and muscular dystrophy (2, 3), suggesting that either glycine metabolism is increased during these conditions, or tissue demand exceeds dietary intake. Our observations in several mouse models of muscle wasting showed that supplementation with glycine preserved muscle mass and metabolic function in a range of conditions where the anabolic response to nutrition was altered (4–6). Glycine administration attenuated skeletal muscle wasting and loss of physical function in a mouse model of cancer cachexia, which was associated with a reduction in protein breakdown and skeletal muscle markers of inflammation and ROS (4). In a mouse model of acute (LPS-induced) inflammation, glycine administration preserved the skeletal muscle anabolic response to leucine, through upregulation of mTORC1 signaling and preservation of protein synthesis. Glycine can affect cell homeostasis via glycine receptor mediated signaling and via its metabolism (7). Indeed, previous reports have linked glycine receptor-mediated signaling, via its scaffolding protein gephyrin, to mTORC1 activation in other tissues (8). In the in vivo LPS model we also showed a reduction in oxidative stress (DHE) but not mRNA expression of pro-inflammatory cytokines and chemokines in skeletal muscle (6). Dietary glycine supplementation in a mouse model of caloric restriction reduced adiposity (whole-body and epididymal fat mass) and preserved lean mass and muscle mass (5). Together, these data revealed a positive effect of glycine treatment on skeletal muscle protein metabolism, mass and function during muscle wasting conditions. However, it is currently unclear whether the beneficial effects of glycine on skeletal muscle are entirely the result of inflammatory cell inactivation, or whether glycine has muscle cell-specific effects. We tested the hypothesis that glycine would directly attenuate myotube wasting in an mTORC1-dependent manner.