Previous results suggest that GSH deficiency is a key factor in the aging process. Recent studies demonstrated that life-long methionine-restriction (MR) increases life span in rats, enhances blood GSH levels in old animals, and prevents the loss of GSH during aging. Our present objectives were to further examine the role of blood GSH in MR-enhanced longevity by determining the time course of GSH changes in blood and other tissues. Male F-344 rats were placed on either a control (0.86% Met) or MR (0.17% Met) defined amino acid diet at 7 wks of age. Six rats from each group were sacrificed monthly over a period of six months. Relative to controls, blood GSH increased 67% and liver GSH declined 66% by 2 months on the MR diet and remained constant thereafter. GSH concentrations in spleen, brain, testis and stomach were unchanged throughout. In a longitudinal study, 9 rats were placed in each diet group at 7 wks of age and retro-orbital blood samples were collected weekly. Blood GSH rose 39% within one week of starting MR and continued to increase for 6 wks until reaching a plateau of 190% of controls. Animals from each group were sacrificed after 4 wks (n=3 per group) and 1] wks (n=6 per group). Decreases in liver, pancreas and kidney GSH occurred within the first 4 wks. When animals were not fasted prior to sacrifice, liver GSH decreased by 80% in MR rats. Fasting reduced liver GSH in controls but had no effect in MR animals, suggesting that MR depletes liver GSH concentrations to a critical level, without adverse effects on longevity. Altogether, these results are consistent with our hypothesis that increased blood GSH, resulting from altered GSH metabolism, contributes to the increased longevity of rats fed a MR diet.
|Original language||English (US)|
|State||Published - Dec 1 1996|
All Science Journal Classification (ASJC) codes
- Molecular Biology