Caloric restriction delays age-related methylation drift

Area of Science:

• Epigenetics
• Gerontology
• Comparative Biology

Background:

• Caloric restriction (CR) is known to extend lifespan across various mammalian species.
• Epigenetic information, particularly DNA methylation, undergoes age-related changes known as epigenetic drift.
• The relationship between epigenetic drift, lifespan, and CR interventions requires further investigation.

Purpose of the Study:

• To investigate the conservation of epigenetic drift across species.
• To determine if the rate of epigenetic drift correlates with lifespan.
• To assess the impact of caloric restriction on age-related DNA methylation drift and its potential to influence lifespan.

Main Methods:

• Comparative analysis of DNA methylation patterns in mice, rhesus monkeys, and humans.
• Longitudinal study of rhesus monkeys and mice subjected to caloric restriction.
• Analysis of DNA methylation age and its correlation with chronological age and gene expression across different tissues.

Main Results:

• Epigenetic drift is conserved across species, with its rate correlating with lifespan.
• Caloric restriction significantly attenuated age-related DNA methylation drift in both rhesus monkeys and mice.
• The intervention resulted in a younger epigenetic age in treated animals compared to controls, with effects observed across multiple tissues and linked to gene expression changes.

Conclusions:

• Epigenetic drift is a conserved biological process that correlates with lifespan in mammals.
• Caloric restriction effectively slows epigenetic drift, potentially by rejuvenating epigenetic information.
• Epigenetic drift may be a key determinant of lifespan, and its modulation by CR offers a potential avenue for interventions targeting aging.