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

Abstract

SummaryCalorie 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.

Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging

“…Caloric restriction (CR), defined as the reduction of calorie intake without malnutrition, is the most reproducible dietary intervention known to promote health and lifespan among model organisms [157]. CR stimulates cardiac autophagy to a greater extent in older vs. younger rodents and humans [122,[158][159][160][161]. The clinical relevance of this strategy is uncertain, however, because strict compliance/self-discipline is required.…”

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

“…Similarly, caloric restriction was found to improve Doppler parameters of diastolic function in B6D2-F1 hybrid mice, a mouse model of senescent diastolic dysfunction, without an impact on systolic parameters (216). In another study that implemented graded regimen for persistent calorie restriction (progressing to 40% reduction as compared with ad-lib) in male C57BL/6J mice beginning at 3, 12 and 19 months of age, the older two age groups demonstrated attenuated age-related cardiac myocyte hypertrophy and fibrosis, accompanied by reduction in markers of fetal gene expression program typically associated with pathologic cardiac hypertrophy; whereas the youngest group of mice paradoxically manifest reduced systolic performance (191). Interestingly, calorie restriction in older mice (and not younger ones) was associated with induction of AMPK signaling, upregulation of FOXO genes and markers indicating increased autophagic flux.…”

Proteomic and structural heart changes in obese rats are incompletely restored after weight loss

“…However, there may be an additional reason for the observed elevation of the heart's connective tissue after weight reduction. CR impacts cardiac morphology in an age-dependent manner by stimulating the fibrotic deposition in young-adult mice (age-matched to our rats), but not in older animals, emphasizing the possible cardiac residue of CR [72].…”