Animal Data for Life Extension via GlyNAC Supplementation

GlyNAC supplementation means addition of glutathione precursors to the diet, glycine and N-acetylcysteine. Glutathione is a natural antioxidant, protective against oxidative stress and able to improve mitochondrial function. Levels of glutatione decline with age, but this can be compensated for via providing increased levels of precursor compounds that will lead to greater manufacture of glutathione. Delivering glutathione directly has been attempted, but doesn't work, for reasons that likely relate to how glutathione ends up in the parts of the cell where it does its work. The interesting data is of course the human data, showing a reduction in chronic inflammation and improvements in other markers, but here find evidence for life extension in mice resulting from this approach.

Determinants of length of life are not well understood, and therefore increasing lifespan is a challenge. Cardinal theories of aging suggest that oxidative stress (OxS) and mitochondrial dysfunction contribute to the aging process, but it is unclear if they could also impact lifespan. Glutathione (GSH), the most abundant intracellular antioxidant, protects cells from OxS and is necessary for maintaining mitochondrial health, but GSH levels decline with aging. Based on published human studies where we found that supplementing glycine and N-acetylcysteine (GlyNAC) improved/corrected GSH deficiency, OxS, and mitochondrial dysfunction, we hypothesized that GlyNAC supplementation could increase longevity.

We tested our hypothesis by evaluating the effect of supplementing GlyNAC vs. placebo in C57BL/6J mice on (a) length of life; and (b) age-associated GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic damage in the heart, liver, and kidneys. Results showed that mice receiving GlyNAC supplementation (1) lived 24% longer than control mice; (2) improved/corrected impaired GSH synthesis, GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic damage. These studies provide proof-of-concept that GlyNAC supplementation can increase lifespan and improve multiple age-associated defects. GlyNAC could be a novel and simple nutritional supplement to improve lifespan and healthspan, and warrants additional investigation.