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.
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.
Miller
Richard A
RA
Department of Pathology, Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, MI 48109-0940, USA. millerr@umich.edu
Buehner
Gretchen
G
Chang
Yayi
Y
Harper
James M
JM
Sigler
Robert
R
Smith-Wheelock
Michael
M
D000082:Acetaminophen / Q000633:toxicity; D000375:Aging / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002386:Cataract / Q000209:etiology / Q000378:metabolism; D004032:Diet; D002149:Energy Intake; D005260:Female; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013974:Thyroxine / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D000082:Acetaminophen; D007334:Insulin-Like Growth Factor I; D008715:Methionine; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse; D013974:Thyroxine