20.500.12556/RUL-158447 Decreasing intracellular entropy by increasing mitochondrial efficiency and reducing ROS formation the effect on the ageing process and age-related damage A hypothesis is presented to explain how the ageing process might be influenced by optimizing mitochondrial efficiency to reduce intracellular entropy. Research-based quantifications of entropy are scarce. Non-equilibrium metabolic reactions and compartmentalization were found to contribute most to lowering entropy in the cells. Like the cells, mitochondria are thermodynamically open systems exchanging matter and energy with their surroundings—the rest of the cell. Based on the calculations from cancer cells, glycolysis was reported to produce less entropy than mitochondrial oxidative phosphorylation. However, these estimations depended on the CO2 concentration so that at slightly increased CO2, it was oxidative phosphorylation that produced less entropy. Also, the thermodynamic efficiency of mitochondrial respiratory complexes varies depending on the respiratory state and oxidant/antioxidant balance. Therefore, in spite of long-standing theoretical and practical efforts, more measurements, also in isolated mitochondria, with intact and suboptimal respiration, are needed to resolve the issue. Entropy increases in ageing while mitochondrial efficiency of energy conversion, quality control, and turnover mechanisms deteriorate. Optimally functioning mitochondria are necessary to meet energy demands for cellular defence and repair processes to attenuate ageing. The intuitive approach of simply supplying more metabolic fuels (more nutrients) often has the opposite effect, namely a decrease in energy production in the case of nutrient overload. Excessive nutrient intake and obesity accelerate ageing, while calorie restriction without malnutrition can prolong life. Balanced nutrient intake adapted to needs/activity-based high ATP requirement increases mitochondrial respiratory efficiency and leads to multiple alterations in gene expression and metabolic adaptations. Therefore, rather than overfeeding, it is necessary to fine-tune energy production by optimizing mitochondrial function and reducing oxidative stress; the evidence is discussed in this paper. entropy disorder randomness ageing mitochondrial function energy efficiency true false true Angleški jezik Ni določen Članek v reviji 2024-06-11 08:03:28 2024-06-11 08:03:30 2024-06-28 03:23:24 0000-00-00 00:00:00 2024 0 0 24 str. iss. 12, art. 6321 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2024-06-07 577:544.322 1422-0067 10.3390/ijms25126321 198345219 ijms-25-06321.pdf ijms-25-06321.pdf 1 9533A668E2E58D81D7A43BB5BF02D21A e13834b462f8eea478eb98847d78bc45ac7fc5f1ed262c7b68dd4f24064e70e5 e065e530-27b8-11ef-b144-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=186076 https://www.mdpi.com/1422-0067/25/12/6321 1 5465eefa-27b8-11ef-b144-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=186075 Zdravstvena fakulteta Medicinska fakulteta 0 0 0