Sex Differences in Response to Diet Enriched With Glutathione Precursors in the Aging Heart

In older male mice, a 12-week diet with glycine and N-acetyl cysteine is linked to higher levels of specific mitochondrial proteins and enzymes, lower levels of damaged proteins, and better heart relaxation; these changes do not occur in older female mice on the same diet.

In older male mice, GlyNAC supplementation increases fibromodulin, a protein that limits collagen fiber formation, resulting in less stiff heart tissue and better heart relaxation during filling, without changing the total amount of collagen.

In older male and female mice, heart cells show more oxidative damage in males than in females. Giving GlyNAC reduces this damage in males but does not reduce it in females.

In older female mice, a diet supplemented with GlyNAC for 12 weeks resulted in decreased exercise endurance, measured by shorter time to exhaustion and lower maximum work output, without improving markers of heart muscle mitochondria.

In older male mice, the activity of the mitochondrial enzyme CrAT is lower than in older female mice. Giving GlyNAC increases CrAT activity in male mice to match the level seen in female mice, without changing how much CrAT protein is present.

In older adults, taking supplements that help the body produce its own antioxidants leads to stronger improvements in biological signs of aging than taking antioxidants directly.