Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents |
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Authors: | Carmen E. Perrone Virginia L. MalloyDavid S. Orentreich Norman Orentreich |
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Affiliation: | Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY 10516, United States |
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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. |
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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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