The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

José Manuel Villalba, José Alberto López-Domínguez, Yana Chen, Husam Khraiwesh, José Antonio González-Reyes, Lucía Fernández del Río, Elena Gutiérrez-Casado, Mercedes del Río, Miguel Calvo-Rubio, Julia Ariza, Rafael de Cabo, Guillermo López-Lluch, Plácido Navas, Kevork Hagopian, María Isabel Burón, Jon J Ramsey

Research output: Contribution to journalArticle

12 Scopus citations

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<sup>+</sup> 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.

Original languageEnglish (US)
Pages (from-to)655-670
Number of pages16
JournalBiogerontology
Volume16
Issue number5
DOIs
StatePublished - Oct 31 2015

Keywords

  • Apoptotic signaling
  • Calorie restriction
  • Dietary fat
  • Lifespan
  • Mitochondria
  • Proton leak

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Aging

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    Villalba, J. M., López-Domínguez, J. A., Chen, Y., Khraiwesh, H., González-Reyes, J. A., del Río, L. F., Gutiérrez-Casado, E., del Río, M., Calvo-Rubio, M., Ariza, J., de Cabo, R., López-Lluch, G., Navas, P., Hagopian, K., Burón, M. I., & Ramsey, J. J. (2015). The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice. Biogerontology, 16(5), 655-670. https://doi.org/10.1007/s10522-015-9572-1