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

J Gerontol A Biol Sci Med Sci. 2015 Apr;70(4):399-409. doi: 10.1093/gerona/glu045. Epub 2014 Apr 1.

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.

Keywords: Apoptosis; Calorie restriction; Dietary fat; Liver..

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Apoptosis* / drug effects
  • Caloric Restriction*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cytochromes c / metabolism
  • Cytosol / drug effects
  • Dietary Fats / metabolism*
  • Genes, bcl-2 / drug effects
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Signal Transduction / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Dietary Fats
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Caspase 3
  • Caspase 8
  • Caspase 9