RT Journal Article T1 Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria A1 Sánchez-Román Rojas, Inés A1 Gómez, Alexia A1 Pérez, Irene A1 Sánchez, Carlota A1 Suárez, Henar A1 Naudí, Alba A1 Jové, Mariona A1 López Torres, Mónica A1 Pamplona, Reinald A1 Barja De Quiroga Losada, Gustavo AB 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 oxidativestress 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 shortterm 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 shortterm exposure to restriction of a single dietary substance: methionine SN 1389-5729 YR 2012 FD 2012 LK https://hdl.handle.net/20.500.14352/98077 UL https://hdl.handle.net/20.500.14352/98077 LA eng NO Sanchez-Roman, I., Gómez, A., Pérez, I. et al. Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria. Biogerontology 13, 399–411 (2012). https://doi.org/10.1007/s10522-012-9384-5 NO Ministerio de Ciencia, Innovación y Universidades (España) NO Generalitat de Catalunya DS Docta Complutense RD 13 abr 2025