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
7 results
Search Results
Now showing 1 - 7 of 7
Item Whole organism aging: Parabiosis, inflammaging, epigenetics, and peripheral and central aging clocks. The ARS of aging(Experimental Gerontology, 2023) Pamplona, Reinald; Jové, Mariona; Gómez, José; Barja De Quiroga Losada, GustavoThe strong interest shown in the study of the causes of aging in recent decades has uncovered many mechanisms that could contribute to the rate of aging. These include mitochondrial ROS production, DNA modification and repair, lipid peroxidation-induced membrane fatty acid unsaturation, autophagy, telomere shortening rate, apoptosis, proteostasis, senescent cells, and most likely there are many others waiting to be discovered. However, all these well-known mechanisms work only or mainly at the cellular level. Although it is known that organs within a single individual do not age at exactly the same rate, there is a well-defined species longevity. Therefore, loose coordination of aging rate among the different cells and tissues is needed to ensure species lifespan. In this article we focus on less known extracellular, systemic, and whole organism level mechanisms that could loosely coordinate aging of the whole individual to keep it within the margins of its species longevity. We discuss heterochronic parabiosis experiments, systemic factors distributed through the vascular system like DAMPs, mitochondrial DNA and its fragments, TF-like vascular proteins, and inflammaging, as well as epigenetic and proposed aging clocks situated at different levels of organization from individual cells to the brain. These interorgan systems can help to determine species longevity as a further adaptation to the ecosystem.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 Mitochondrial ROS production, oxidative stress and aging within and between species: Evidences and recent advances on this aging effector(Experimental Gerontology, 2023) Gómez, José; Mota Martorell, Natalia; Jové, Mariona; Pamplona, Reinald; Barja De Quiroga Losada, GustavoMitochondria play a wide diversity of roles in cell physiology and have a key functional implication in cell bioenergetics and biology of free radicals. As the main cellular source of oxygen radicals, mitochondria have been postulated as the mediators of the cellular decline associated with the biological aging. Recent evidences have shown that mitochondrial free radical production is a highly regulated mechanism contributing to the biological determination of longevity which is species-specific. This mitochondrial free radical generation rate induces a diversity of adaptive responses and derived molecular damage to cell components, highlighting mitochondrial DNA damage, with biological consequences that influence the rate of aging of a given animal species. In this review, we explore the idea that mitochondria play a fundamental role in the determination of animal longevity. Once the basic mechanisms are discerned, molecular approaches to counter aging may be designed and developed to prevent or reverse functional decline, and to modify longevity.Item 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.