Methionine restriction increases blood glutathione and longevity in F344 rats

  title={Methionine restriction increases blood glutathione and longevity in F344 rats},
  author={John P. Richie and Yvonne Leutzinger and Saudhamini Parthasarathy and Virginia Maixoy and Norman Orentreich and Jay A. Zimmerman},
  journal={The FASEB Journal},
  pages={1302 - 1307}
Little is known about the biochemical mechanisms responsible for the biological aging process. Our previous results and those of others suggest that one possible mechanism is based on the loss of glutathione (GSH), a multifunctional tripeptide present in high concentrations in nearly all living cells. The recent finding that life‐long dietary restriction of the GSH precursor methionine (Met) resulted in increased longevity in rats led us to hypothesize that adaptive changes in Met and GSH… 

Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat

Findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.

Altered dietary methionine differentially impacts glutathione and methionine metabolism in long-living growth hormone-deficient Ames dwarf and wild-type mice

This component analysis between Ames and wild-type mice suggests that the life span differences observed may result from the atypical MET metabolism and downstream effects on multiple systems, indicating the importance of GH signaling in the ability to discriminate dietary amino acid levels.

Effect of calorie restriction on liver and kidney glutathione in aging emory mice

Calorie restriction reduces the age-related loss of GSH antioxidant capacity in liver but not kidney of Emory mice, and total liver glutathione was higher in R than in C mice at 22 mo old.

Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria

Treating old rats with isocaloric short-term MetR lowers mitROS production and free radical leak and oxidative damage to mtDNA, and reverses aging-related increases in protein modification.

Effects of Aging and Methionine Restriction on Rat Kidney Metabolome

A mass spectrometry-based high-throughput metabolomic and lipidomic profiling was undertaken of renal cortex samples of three groups of male rats, showing minor changes during aging in the renal cortex metabolome, with less than 59 differential metabolites between the Adult and Aged groups.



Blood glutathione: a biochemical index of life span enhancement in the diet restricted Lobund-Wistar rat.

The experimental results demonstrate that dietary restriction in both conventional and germfree rats results in enhanced longevity compared to fullfed animals and suggests that glutathione may be a molecular mechanism for the diet restriction and longevity phenomenon.

Correction of a Glutathione Deficiency in the Aging Mosquito Increases Its Longevity

  • J. RichieB. MillsC. Lang
  • Medicine
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1987
Findings confirm the GSH deficiency hypothesis and demonstrate a specific biochemical mechanism of aging that can be nutritionally modified.

Life span profiles of glutathione and acetaminophen detoxification.

Findings demonstrate clearly the occurrence of decreased detoxification capacity in the GSH-deficient, aging mouse.

Glutathione contents of tissues in the aging mouse.

Results extend the previous results and indicate that a general characteristic of aging tissues may be a decrease in GSH concentrations, consistent with the hypothesis that the reducing potential of tissues decreases in senescence.

Protein oxidation associated with aging is reduced by dietary restriction of protein or calories.

Protein restriction reduced the accumulation of oxidatively damaged proteins during the oxidative stress of chronic irradiation, and oxidative damage to proteins increased with aging and with radiation.

Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics.

Compared with that limited to early life or involving most of the life span on physical, metabolic, and longevity characteristics, food restriction does not act by reducing the intake of calories or other nutrient per gram of body mass, a finding not in accord with classic views.

The effect of diet on the glutathione content of erythrocytes.

  • R. Mortensen
  • Biology, Medicine
    The Journal of biological chemistry
  • 1953

The Effect of Aging on Glutathione and Cysteine Levels in Different Regions of the Mouse Brain

  • T. ChenJ. RichieC. Lang
  • Biology
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1989
A GSH deficiency in brain tissues of aging mice like that found previously in other tissues is demonstrated and an increased susceptibility of the aging brain to oxidative damage is suggested.

Effect of chronic food restriction in aging rats II. Liver cytosolic antioxidants and related enzymes

Glutathione Levels during the Mosquito Life Span with Emphasis on Senescence

  • G. A. HazeltonC. Lang
  • Medicine
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1984
Glutathione levels were determined in mosquitoes of all ages of the life span, and the highest levels of GSH and total glutathione were found during larval growth and metamorphosis, which can lead to lower biosynthetic activity and also impaired detoxification capacity.