Opposing effects on cardiac function by calorie restriction in different-aged mice

Aging Cell. 2017 Oct;16(5):1155-1167. doi: 10.1111/acel.12652. Epub 2017 Aug 11.

Abstract

Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age-related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study. C57BL/6 mice were subjected to a calorically restricted diet (40% less than the ad libitum diet) for 3 months initiated in 3, 12, and 19 months. It was found that CR significantly reversed the aging phenotypes of middle-aged and old mice including cardiac remodeling (cardiomyocyte hypertrophy and cardiac fibrosis), inflammation, mitochondrial damage, telomere shortening, as well as senescence-associated markers but accelerated in young mice. Furthermore, whole-genome microarray demonstrated that the AMP-activated protein kinase (AMPK)-Forkhead box subgroup 'O' (FOXO) pathway might be a major contributor to contrasting regulation by CR initiated in different ages; thus, increased autophagy was seen in middle-aged and old mice but decreased in young mice. Together, the findings demonstrated promising myocardial protection by 40% CR should be initiated in middle or old age that may have vital implications for the practical nutritional regimen.

Keywords: AMPK; FOXO; autophagy; calorie restriction; cardiac aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • AMP-Activated Protein Kinases / metabolism
  • Aging / genetics*
  • Aging / metabolism*
  • Animals
  • Autophagy / genetics
  • Body Weight
  • Caloric Restriction / methods*
  • Forkhead Box Protein O1 / genetics*
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Heart Function Tests
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microarray Analysis
  • Myocardium / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction
  • Time Factors

Substances

  • Forkhead Box Protein O1
  • MicroRNAs
  • Protein Isoforms
  • AMP-Activated Protein Kinases