title: Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria.
abstract: It is known that a global decrease in food ingestion (dietary restriction, DR) lowers mitochondrial ROS generation (mitROS) and oxidative stress in young immature rats. This seems to be caused by the decreased methionine ingestion of DR animals. This is interesting since isocaloric methionine restriction in the diet (MetR) also increases, like DR, rodent maximum longevity. However, it is not known if old rats maintain the capacity to lower mitROS generation and oxidative stress in response to MetR similarly to young immature animals, and whether MetR implemented at old age can reverse aging-related variations in oxidative stress. In this investigation the effects of aging and 7 weeks of MetR were investigated in liver mitochondria of Wistar rats. MetR implemented at old age decreased mitROS generation, percent free radical leak at the respiratory chain and mtDNA oxidative damage without changing oxygen consumption. Protein oxidation, lipoxidation and glycoxidation increased with age, and MetR in old rats partially or totally reversed these age-related increases. Aging increased the amount of SIRT1, and MetR decreased SIRT1 and TFAM and increased complex IV. No changes were observed in the protein amounts of PGC1, Nrf2, MnSOD, AIF, complexes I, II and III, and in the extent of genomic DNA methylation. In conclusion, 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. Aged rats maintain the capacity to lower mitochondrial ROS generation and oxidative stress in response to a short-term exposure to restriction of a single dietary substance: methionine.
authors.affiliation: Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Sanchez-Roman
authors.forename: Alexia
authors.initials: A
authors.lastname: Gómez
authors.forename: Irene
authors.initials: I
authors.lastname: Pérez
authors.forename: Carlota
authors.initials: C
authors.lastname: Sanchez
authors.forename: Henar
authors.initials: H
authors.lastname: Suarez
authors.forename: Alba
authors.initials: A
authors.lastname: Naudí
authors.forename: Mariona
authors.initials: M
authors.lastname: Jové
authors.forename: Mónica
authors.initials: M
authors.lastname: Lopez-Torres
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.forename: Gustavo
authors.initials: G
authors.lastname: Barja
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008930:Mitochondria, Liver / Q000201:enzymology*; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C489030:Tfam protein, rat; D014157:Transcription Factors; D008715:Methionine; D013482:Superoxide Dismutase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1