METHIONINE RESTRICTION INCREASES BLOOD GLUTATHIONE AND LONGEVITY IN F344 RATS

Little is known about the biochemical mechanisms responsible for the b iological aging process. Our previous results and those of others sugg est that one possible mechanism is based on the loss of glutathione (G SH), a multifunctional tripeptide present in high concentrations in ne arly all living cells. The recent finding that life-long dietary restr iction of the GSH precursor methionine (Met) resulted in increased lon gevity in rats led us to hypothesize that adaptive changes in Met and GSH metabolism had occurred, leading to enhanced GSH status. To test t his, blood and tissue GSH levels were measured at different ages throu ghout the life span in E344 rats on control or Met-restricted diets. M et restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls ( P < 0.001). Increases in blood GSH levels of 81% and 164% were observe d in mature and old Met-restricted animals, respectively (P < 0.001). Liver was apparently the source for this increase as hepatic GSH level s decreased to 40% of controls. Except for a 25% decrease in kidney, G SH was unchanged in other tissues. All changes in GSH occurred as earl y as 2 months after the start of the diet. Altogether, these results s uggest that dramatic adaptations in sulfur amino acid metabolism occur as a result of chronic Met restriction, leading to increases in blood GSH levels and conservation of tissue GSH during aging.-Richie, J. P. , Jr, Leutzinger, Y., Parthasarathy, S., Malloy, V., Orentreich, N., Z immerman, J. A. Methionine restriction increases blood glutathione and longevity in F344 rats.