Changes in the intracellular homocysteine and glutathione content associated with aging

Since moderate hyperhomocysteinemia is an independent risk factor for vascu lar disease by mean of its oxidant effect and glutathione plays a main role as intracellular redox-regulating agent, we have studied for the first tim e the total intracellular content of homocysteine in aging. Plasma homocyst eine concentration, total intracellular and plasma glutathione, and other r elated thiol compounds such as cysteine and the glutathione catabolite cyst einglycine were also studied, Forty three healthy elderly subjects and twen ty seven healthy young ones were studied. The total intracellular periphera l blood mononuclear cell content was higher for homocysteine, cysteine and cysteinglycine, whereas that of the total glutathione was greatly decreased in elderly people with respect to young ones. Elderly subjects showed sign ificantly higher levels than young ones of total plasma homocysteine and cy steinglycine, but not cysteine, whereas total plasma glutathione levels wer e increased. In addition, elderly subjects showed significantly decreased p lasma vitamin E levels and increased concentrations of serum lipid peroxide s measured as TEARS (reaction product of malondialdehyde with thiobarbituri c acid). The intracellular glutathione content presented significantly nega tive correlation with serum TEARS, and intracellular and plasma homocystein e levels, These findings show an increase of homocysteine synthesis associa ted with aging, which in turn can produce an augmented oxidant effect on en dothelium, and an impaired intracellular antioxidant capacity leading to an enhanced lipid peroxidation and decreased total intracellular glutathione content. (C) 2000 Elsevier Science Inc, All rights reserved.