Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance

Aging Cell. 2005 Jun;4(3):119-25. doi: 10.1111/j.1474-9726.2005.00152.x.


A diet deficient in the amino acid methionine has previously been shown to extend lifespan in several stocks of inbred rats. We report here that a methionine-deficient (Meth-R) diet also increases maximal lifespan in (BALB/cJ x C57BL/6 J)F1 mice. Compared with controls, Meth-R mice have significantly lower levels of serum IGF-I, insulin, glucose and thyroid hormone. Meth-R mice also have higher levels of liver mRNA for MIF (macrophage migration inhibition factor), known to be higher in several other mouse models of extended longevity. Meth-R mice are significantly slower to develop lens turbidity and to show age-related changes in T-cell subsets. They are also dramatically more resistant to oxidative liver cell injury induced by injection of toxic doses of acetaminophen. The spectrum of terminal illnesses in the Meth-R group is similar to that seen in control mice. Studies of the cellular and molecular biology of methionine-deprived mice may, in parallel to studies of calorie-restricted mice, provide insights into the way in which nutritional factors modulate longevity and late-life illnesses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaminophen / toxicity
  • Aging / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Cataract / etiology
  • Cataract / metabolism
  • Diet
  • Energy Intake
  • Female
  • Insulin / blood
  • Insulin-Like Growth Factor I / metabolism
  • Intramolecular Oxidoreductases
  • L-Lactate Dehydrogenase / blood
  • Liver / drug effects
  • Liver / metabolism
  • Longevity / physiology*
  • Macrophage Migration-Inhibitory Factors / genetics
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Methionine / deficiency*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • RNA, Messenger / metabolism
  • T-Lymphocyte Subsets / metabolism
  • Thyroxine / blood


  • Blood Glucose
  • Insulin
  • Macrophage Migration-Inhibitory Factors
  • RNA, Messenger
  • Acetaminophen
  • Insulin-Like Growth Factor I
  • Methionine
  • L-Lactate Dehydrogenase
  • Alanine Transaminase
  • Intramolecular Oxidoreductases
  • Mif protein, mouse
  • Thyroxine