Person: Barja De Quiroga Losada, Gustavo
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First Name
Gustavo
Last Name
Barja De Quiroga Losada
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Genética, Fisiología y Microbiología
Area
Fisiología
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Item Independent and additive effects of atenolol and methionine restriction on lowering rat heart mitochondria oxidative stress(Journal of Bioenergetics and Biomembranes, 2014) Sánchez-Román Rojas, Inés; Gómez, Alexia; Naudí, Alba; Jové, Mariona; Gómez, Jose; López Torres, Mónica; Pamplona, Reinald; Barja De Quiroga Losada, GustavoItem Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria(Biogerontology, 2012) Sánchez-Román Rojas, Inés; Gómez, Alexia; Pérez, Irene; Sánchez, Carlota; Suárez, Henar; Naudí, Alba; Jové, Mariona; López Torres, Mónica; Pamplona, Reinald; Barja De Quiroga Losada, GustavoIt 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 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: methionineItem Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction(Experimental Gerontology, 2013) Sánchez-Román Rojas, Inés; Barja De Quiroga Losada, GustavoComparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA.Item Reduction in mitochondrialmembrane peroxidizability index and protein lipoxidation levels in therat heart after ß-adrenergic receptor signaling interruption with the ß-blocker atenolol(Anales de la Real Academia Nacional de Farmacia, 2013) Gomez, Alexia; Sánchez-Román Rojas, Inés; Gomez, Jose; Naudí, Alba; Pushparaj, Charumati; Portero-Otín, Manuel; López Torres, Mónica; Pamplona, Reinald; Barja De Quiroga Losada, GustavoItem Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity(Aging Cell, 2014) Gómez, Alexia; Sánchez-Román Rojas, Inés; Gomez, Jose; Cruces, Julia; Mate, Ianire; López Torres, Mónica; Naudi, Alba; Portero-Otín, Manuel; Pamplona, Reinald; Fuente Del Rey, María Mónica De La; Barja De Quiroga Losada, GustavoThe membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals. This was mainly due to decreases in 22:6n-3 and increases in 18:1n-9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug.