Caloric restriction and aging: studies in mice and monkeys

Area of Science:

• Gerontology
• Metabolic research
• Molecular biology

Background:

• Caloric restriction (CR) without malnutrition is known to delay aging and extend lifespan across various species.
• The precise molecular mechanisms driving these CR-induced benefits remain largely unknown.
• A leading hypothesis suggests that reprogramming of energy metabolism is central to CR's effects.

Purpose of the Study:

• To investigate the effects of long-term caloric restriction (CR) on energy metabolism and gene expression in white adipose tissue (WAT).
• To examine whether CR retards aging in primates, specifically rhesus monkeys.
• To determine if CR impacts age-associated muscle loss (sarcopenia) in non-human primates.

Main Methods:

• Studies involving mice subjected to long-term CR.
• Analysis of gene expression profiles in mouse epididymal WAT.
• Long-term CR intervention study in rhesus monkeys initiated in 1989.

Main Results:

• Long-term CR significantly alters gene expression in WAT, increasing genes involved in energy metabolism.
• CR down-regulates over 50 pro-inflammatory genes in WAT.
• A 30% reduction in energy intake in mice and monkeys decreased adiposity by approximately 70%.
• CR was found to reduce the rate of age-associated muscle loss (sarcopenia) in rhesus monkeys.

Conclusions:

• Reprogramming of energy metabolism, evidenced by gene expression changes in WAT, is a key mechanism of CR.
• Long-term CR demonstrably reduces adiposity and inflammation.
• CR shows promise in mitigating age-associated muscle loss in primates, suggesting potential anti-aging benefits in humans.