Multi-tissue DNA methylation age predictor in mouse.

Area of Science:

• Genomics
• Epigenetics
• Aging Research

Background:

• DNA methylation patterns correlate with chronological and biological age in humans.
• It remains unclear if these epigenetic changes cause aging or are a result of it.
• The conservation of epigenetic clocks across species, particularly in mice, has not been established.

Purpose of the Study:

• To develop and characterize an epigenetic clock for mice.
• To assess the conservation of epigenetic aging predictors between humans and mice.
• To utilize the mouse epigenetic clock for studying aging biology and interventions.

Main Methods:

• Generation of genome-scale, base-resolution DNA methylation maps from diverse mouse tissues across a range of ages.
• Development of a multi-tissue age prediction model using 329 unique CpG sites.
• Analysis of publicly available datasets to validate the mouse clock's accuracy and assess biological age effects.

Main Results:

• A robust multi-tissue mouse epigenetic clock was developed with a median absolute error of 3.33 weeks.
• The mouse clock demonstrates similar properties to the human epigenetic clock.
• The clock accurately measures biological age changes due to interventions like ovariectomy and diet.
• No significant sex-based differences in predicted DNA methylation age were observed.

Conclusions:

• An epigenetic predictor of age, the mouse epigenetic clock, has been identified and characterized.
• This mouse clock is a valuable tool for understanding aging biology.
• The clock will enable in vivo studies on modulating aging rates and resetting biological age.