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

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Calorie restriction (CR) benefits the aging heart when started in middle or old age, reversing age-related damage. However, initiating CR in young mice accelerates aging, highlighting the critical timing for cardiac protection.

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AMPKFOXOautophagycalorie restrictioncardiac aging

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Area of Science:

  • Gerontology
  • Cardiovascular Science
  • Nutritional Science

Background:

  • Calorie restriction (CR) is known to extend lifespan and improve healthspan.
  • CR's effects on cardiac aging and ischemic tolerance vary depending on initiation age.
  • Optimal timing for CR to benefit cardiac remodeling and function during aging is not well-defined.

Purpose of the Study:

  • To investigate the impact of initiating CR at different ages (3, 12, and 19 months) on myocardial protection in mice.
  • To determine if CR exerts similar effects on cardiac aging regardless of initiation age.
  • To elucidate the molecular mechanisms underlying age-dependent CR effects on the heart.

Main Methods:

  • C57BL/6 mice were subjected to a 40% CR diet for 3 months, initiated at 3, 12, or 19 months of age.
  • Evaluated cardiac remodeling, inflammation, mitochondrial function, telomere length, and senescence markers.
  • Utilized whole-genome microarray to analyze gene expression, focusing on the AMPK-FOXO pathway and autophagy.

Main Results:

  • CR reversed aging phenotypes in middle-aged and old mice, including cardiac remodeling, inflammation, mitochondrial damage, and senescence.
  • CR accelerated aging phenotypes in young mice.
  • CR modulated the AMPK-FOXO pathway and autophagy differently based on initiation age, with increased autophagy in older mice and decreased autophagy in younger mice.

Conclusions:

  • Initiating a 40% CR diet in middle or old age provides significant myocardial protection and reverses cardiac aging.
  • Initiating CR in young mice appears detrimental, potentially accelerating aging processes.
  • Timing of CR initiation is crucial for its cardioprotective effects, with middle or old age being optimal for benefits.