Preliminary experiments suggested lifespan extension by glycine supplementation (GlyS) without the growth inhibition seen with methionine restriction in Fisher 344 rats. This suggested that the benefit GlyS, rather than owing to increased methionine clearance (as was originally envisioned), was attributable to increased levels of glycine itself, acting via the glycine receptor. The glycine receptor is a glycine‐gated chloride channel that is widespread among cell types, including macrophages, and GlyS has been shown by others to exhibit anti‐inflammatory and anti‐cancer properties in several rodent models, and even to reverse Type 2 diabetes in a human trial. GlyS has also recently been found by others to restore the youthful mitochondrial phenotype in senescent cultured human fibroblasts, whose senescence was linked to epigenetic down‐regulation of the principal pathways of endogenous glycine synthesis. The present study set out to replicate the life extension previously observed in rats, in large, reproducible populations of UM‐HET‐3, 4‐way cross mice, in a Phase I Interventions Testing Program (ITP) trial of the National Institute on Aging (NIA). Beginning at 9 months of age, GlyS mice were fed a diet containing 8% glycine (dry weight, compared to the level of 2.3% in the control diet) simultaneously at 3 sites (The Jackson Labs, Bar Harbor, ME; University of Michigan, Ann Arbor, MI; U.T. Health San Antonio, TX), employing approximately 50 each of male and female GlyS and 100 each of male and female controls at each site. Data were compiled after 90% of control mice had died at all 3 sites. Pooling data from all 3 sites (shown in Figure below), median lifespan was increased among GlyS mice by 3.7% among females and 1.3% among males, and the 90th percentile lifespan was increased by 1.8% among females and 3.6% among males (p = 0.00004 by log‐rank test and p = 0.002 by Wang‐Allison test for pooled males and females at all 3 sites combined). The observed lifespan extension is statistically robust, in that significant log‐rank p‐values were seen for each sex (pooling across site) and for each site (pooling across sexes). The Stage I ITP protocol measures only lifespan, and it is anticipated that Stage II trials will provide the opportunity for biochemical and other cross‐sectional measures to elucidate the mechanism(s) involved in the life extension observed in our system.

Support or Funding Information

Interventions Testing Program, National Institute on Aging

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.