Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation

Abstract

Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging.

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…Sekhar and colleagues measured erythrocyte glutathione levels in eight elderly subjects (aged 60-75 years) and in eight younger subjects (aged 30-40 years); they were 46 % lower in the older group (Sekhar et al 2011). Erythrocyte cysteine levels in the elderly subjects were more moderately depressed-by 24 %.…”

“…Cysteine availability is rate-limiting for glutathione synthesis (Richman and Meister 1975;Suh et al 2004a). In this regard, there is considerable evidence that glutathione synthesis and glutathione tissue levels tend to decline in rodents and humans as they age (Suh et al 2004a;Rebrin and Sohal 2008;Rebrin et al 2007;Droge et al 2006;Sekhar et al 2011;Wang et al 2003;Lean et al 2005). This appears to reflect, in turn, an age-related decline in expression and function of the Nrf2 transcription factor (Suh et al 2004a;Suh et al 2004b;Ungvari et al 2011;Shih and Yen 2007).…”

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

“…Indeed, although not confirmed in endothelial cells, FAO-derived acetyl-CoA entering the tricarboxylic acid cycle is converted to malate and citrate, metabolites that are the respective substrates for the NADPH-producing malic enzyme and for isocitrate dehydrogenases 1 and -2 (Jeon et al, 2012). The resultant NADPH might replenish GSH, which is a strong ROS scavenger and forms one of the main cellular defenses against oxidative stress (Jongkind et al, 1989;Sekhar et al, 2011). Although evidence shows that FAO is important for endothelial cell function, the specific mechanisms that FAO mediates during angiogenesis remain undetermined.…”

Antioxidants

“…There are food sources of ALA such as yeast, organ meats like liver and heart, spinach, broccoli, and potatoes. The study of Dell'Anna et al demonstrate; Oral supplementation of alpha-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB and reducing vitiligo associated oxidative stress [49].…”