A multi-tissue full lifespan epigenetic clock for mice.

Area of Science:

• Aging research
• Epigenetics
• Mammalian biology

Background:

• Epigenetic clocks are accurate human aging biomarkers.
• Mouse epigenetic clocks can be slowed by interventions like calorie restriction.
• Novel mouse epigenetic clocks are needed to study aging and interventions.

Purpose of the Study:

• To develop and compare novel mouse epigenetic clocks.
• To assess the impact of different regression models and CpG sets on clock accuracy and intervention detection.
• To investigate trade-offs between clock accuracy and sensitivity to anti-aging effects.

Main Methods:

• Utilized DNA methylation data from 1189 mouse samples.
• Developed four novel epigenetic clocks using elastic net and ridge regression.
• Compared clocks built on all CpG sites versus highly conserved CpG sites.

Main Results:

• Accurate age estimators were developed using conserved CpGs.
• The most accurate clock used elastic net regression on all CpGs.
• Calorie restriction's anti-aging effects were detected by all clocks.
• Ridge regression clocks detected slow aging in dwarf mice, unlike elastic net clocks.

Conclusions:

• Mouse epigenetic clocks offer insights into aging and interventions.
• Trade-offs exist between clock accuracy and sensitivity to anti-aging interventions.
• Highly accurate clocks may not be optimal for detecting intervention benefits.