title: Dietary fat and aging modulate apoptotic signaling in liver of calorie-restricted mice.
abstract: Imbalance between proliferation and cell death accounts for several age-linked diseases. Aging, calorie restriction (CR), and fat source are all factors that may influence apoptotic signaling in liver, an organ that plays a central metabolic role in the organism. Here, we have studied the combined effect of these factors on a number of apoptosis regulators and effectors. For this purpose, animals were fed diets containing different fat sources (lard, soybean oil, or fish oil) under CR for 6 or 18 months. An age-linked increase in the mitochondrial apoptotic pathway was detected with CR, including a decrease in Bcl-2/Bax ratio, an enhanced release of cytochrome c to the cytosol and higher caspase-9 activity. However, these changes were not fully transmitted to the effectors apoptosis-inducing factor and caspase-3. CR (which abated aging-related inflammatory responses) and dietary fat altered the activities of caspases-8, -9, and -3. Apoptotic index (DNA fragmentation) and mean nuclear area were increased in aged animals with the exception of calorie-restricted mice fed a lard-based fat source. These results suggest possible protective changes in hepatic homeostasis with aging in the calorie-restricted lard group.
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: López-Domínguez
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain.
authors.forename: Husam
authors.initials: H
authors.lastname: Khraiwesh
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: González-Reyes
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, and CIBERER, Instituto de Salud Carlos III, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Lluch
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, and CIBERER, Instituto de Salud Carlos III, Sevilla, Spain.
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.affiliation: VM Molecular Biosciences, University of California, Davis.
authors.forename: Jon Jay
authors.initials: JJ
authors.lastname: Ramsey
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Burón
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Córdoba, Spain. jmvillalba@uco.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Villalba
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D031204:Caloric Restriction; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects; D004041:Dietary Fats / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: Apoptosis; Calorie restriction; Dietary fat; Liver.