Evidence suggests that ageing and disease are associated with increased oxidative stress. The cause and effect of this relationship is not fully understood, but oxidative stress has been linked to immune dysfunction, increased risk of cataracts, neurodegeneration, obesity, metabolic syndrome, diabetes, cancer and cardiovascular disease. Nutrients have been extensively researched with respect to their role in decreasing systemic oxidative stress, and generally the literature has shown a positive effect from dietary antioxidants. Endogenous antioxidant compounds such as lipoic acid, NADPH, coenzyme Q10 and glutathione are also important in maintaining favourable reducing conditions within cells and are therefore important components of the cellular redox system. Of these, glutathione has been extensively researched with regard its effects on disease and aging. Glutathione levels tend to decrease with age and decreased levels of glutathione are associated with immune system dysfunction and cell damage.
Glutathione is a tripeptide compound, and is synthesised endogenously in humans from the amino acids glycine, glutamate and cysteine in a series of reactions catalysed by the enzyme glutamate cysteine ligase (γ-glutamylcysteine synthase) and γ-L-glutamyl-L-cysteine:glycine ligase (glutathione synthetase). Interestingly, glutathione levels in the elderly can be increased by supplementation with the precursor amino acids, L-cysteine or L-glycine. For example, Researchers1 have investigated the oral supplementation of 0.81mmol cysteine·kg-1·d-1 (as n-acetylcysteine) and 1.33mmolglycine·kg-1·d-1 for 14 days in 8 elderly (60 to 75 years) and 8 younger subjects (30 to 40 years). Subjects consumed a normal diet, but fasted for 10 hours before the rate of glutathione synthesis was assessed by the of the incorporation of an infused stable isotopes of glycine ([2H2]glycine) into erythrocytes. Researchers then assessed the levels of oxidative stress by measuring markers of oxidative stress in the subjects.
At baseline, erythrocyte concentrations of glycine, cysteine and glutathione were significantly lower in elderly compared to younger subjects. However, supplementation with n-acetylcysteine and L-glycine increased erythrocyte concentrations of glycine and cysteine by 117.6 and 55.1%. respectively. Supplementation also caused a 94.6% increase in erythrocyte glutathione levels compared to pre-supplementation levels. Post-supplementation there was no significant difference between the younger and elderly subjects with regard their glutathione:GSSG ratios. The slower (pre-supplementation) rate of glutathione synthesis in elderly subjects was also associated with higher concentrations of the markers of oxidative stress plasma F2-isoprotsane and lipid peroxides. Supplementation with the amino acids however, caused a significant reduction in these levels to similar values as the younger subjects. Supplementation of the precursors of glutathione are therefore beneficial to elderly subjects, perhaps because of age-related decreases in endogenous glycine and cysteine synthesis, or reduce protein turnover.
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