1. The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice.
- Author
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Villalba JM, López-Domínguez JA, Chen Y, Khraiwesh H, González-Reyes JA, Del Río LF, Gutiérrez-Casado E, Del Río M, Calvo-Rubio M, Ariza J, de Cabo R, López-Lluch G, Navas P, Hagopian K, Burón MI, and Ramsey JJ
- Subjects
- Age Factors, Aging pathology, Apoptosis, Dietary Fats metabolism, Electron Transport Chain Complex Proteins metabolism, Fish Oils administration & dosage, Fish Oils metabolism, Lipid Peroxidation, Longevity, Membrane Potential, Mitochondrial, Mitochondria, Liver ultrastructure, Mitochondria, Muscle ultrastructure, Models, Biological, Muscle, Skeletal ultrastructure, Oxidative Stress, Reactive Oxygen Species metabolism, Soybean Oil administration & dosage, Soybean Oil metabolism, Time Factors, Aging metabolism, Caloric Restriction, Dietary Fats administration & dosage, Mitochondria, Liver metabolism, Mitochondria, Muscle metabolism, Muscle, Skeletal metabolism
- Abstract
The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40 % less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H(+) leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40 % CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.
- Published
- 2015
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