Dietary fat and aging modulate apoptotic signaling in liver of calorie-restricted mice

José Alberto López-Domínguez, Husam Khraiwesh, José Antonio González-Reyes, Guillermo López-Lluch, Plácido Navas, Jon J Ramsey, Rafael De Cabo, María Isabel Burón, José Manuel Villalba

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)399-409
Number of pages11
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume70
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Apoptosis
  • Calorie restriction
  • Dietary fat-Liver

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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    López-Domínguez, J. A., Khraiwesh, H., González-Reyes, J. A., López-Lluch, G., Navas, P., Ramsey, J. J., De Cabo, R., Burón, M. I., & Villalba, J. M. (2015). Dietary fat and aging modulate apoptotic signaling in liver of calorie-restricted mice. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 70(4), 399-409. https://doi.org/10.1093/gerona/glu045