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Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents
Authors:Carmen E. Perrone  Virginia L. MalloyDavid S. Orentreich  Norman Orentreich
Affiliation:Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY 10516, United States
Abstract:Restriction of dietary methionine by 80% slows the progression of aged-related diseases and prolongs lifespan in rodents. A salient feature of the methionine restriction phenotype is the significant reduction of adipose tissue mass, which is associated with improvement of insulin sensitivity. These beneficial effects of MR involve a host of metabolic adaptations leading to increased mitochondrial biogenesis and function, elevated energy expenditure, changes of lipid and carbohydrate homeostasis, and decreased oxidative damage and inflammation. This review summarizes observations from MR studies and provides insight about potential mediators of tissue-specific responses associated with MR's favorable metabolic effects that contribute to health and lifespan extension.
Keywords:ACC, acetyl-CoA carboxylase   Ahcy, adenosylhomocysteinase   AT, adipose tissue   ATGL, adipose triglyceride lipase   AMPK, AMP-activated protein kinase   Bhmt, betaine-homocysteine S-methyltransferase   CR, caloric restriction   CBS, cystathionine β-synthase   Ccl7, chemokine (C-C motif) ligand 7   CF, control-fed   Cth, cystathionase   Ccr2 and Ccr5, chemokine (C-C motif) receptors 2 and 5   FGF21, fibroblast growth factor 21   F344, Fischer 344   FRL, free radical leak   Gclm, glutamine&ndash  cysteine ligase   Gpd2, glycerophosphate dehydrogenase 2   Gnmt, glycine N-methyltransferase   GH, growth hormone   IGF-1, insulin-like growth factor-1   Lbp, lipopolysaccharide binding protein   Mat1a, methionine adenosyltransferase 1 alpha   Mtr, methionine synthase   MR, methionine restriction   8-oxo-dG, 8-oxo-deoxyguanosine   PPARs, peroxisome proliferator-activated receptors   PGC1, peroxisome proliferator-activated receptor coactivator 1   PR, protein restriction   ROS, reactive oxygen species   SAH, S-adenosylhomocysteine   SAM, S-adenosylmethionine   Sirt1, sirtuin 1   Scd1, stearoyl-CoA desaturase-1   TG, triglyceride   TNFα, tumor necrosis factor-alpha   UCP1, uncoupling protein-1   WAT, white adipose tissue
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