An epigenetic clock for human skeletal muscle.

Area of Science:

• Epigenetics
• Gerontology
• Molecular Biology

Background:

• Aging is linked to DNA methylation changes across human tissues.
• Existing epigenetic clocks show significant age prediction errors in skeletal muscle.
• This limitation stems from the exclusion of muscle samples in prior clock development.

Purpose of the Study:

• To develop a precise, skeletal muscle-specific epigenetic clock for age estimation.
• To identify age-associated DNA methylation patterns in skeletal muscle.
• To improve the accuracy of biological age prediction in muscle tissue.

Main Methods:

• Genome-wide DNA methylation data from 682 skeletal muscle samples were analyzed.
• Data were sourced from 12 independent datasets using Illumina HumanMethylation arrays.
• An epigenome-wide association study was conducted on age-related methylation patterns.

Main Results:

• A novel muscle clock using 200 CpG sites was developed, outperforming the pan-tissue clock.
• The muscle clock achieved a median error of 4.6 years, compared to 13.1 years for the pan-tissue clock.
• 180 differentially methylated regions associated with age in skeletal muscle were identified.

Conclusions:

• A highly accurate muscle-specific epigenetic clock has been created.
• The clock is available as an R package (Muscle Epigenetic Age Test) for broader use.
• This tool can help assess environmental impacts on muscle aging, such as exercise and diet.