Epigenetic mutation load is weakly correlated with epigenetic age acceleration

Area of Science:

• Epigenetics
• Genomics
• Aging Research

Background:

• DNA methylation (DNAm) age is a key biomarker for aging.
• The relationship between DNAm age and stochastic epigenetic mutations (SEMs) is unclear.
• SEMs may indicate epigenetic maintenance system dysfunction.

Purpose of the Study:

• To define and assess epigenetic mutation load (EML).
• To investigate the association between EML and DNAm age acceleration.
• To identify biological pathways and genomic regions associated with EML and age acceleration.

Main Methods:

• Defined EML as the total number of SEMs per individual.
• Analyzed associations between EML and four DNAm age acceleration estimators in 6,388 participants across four studies.
• Conducted pathway enrichment analyses and examined genomic-region specific EML.

Main Results:

• EML positively correlated with chronological age (meta r = 0.171).
• EML associated with four epigenetic age acceleration measures (r ranging from 0.109 to 0.179).
• SEMs implicated signaling, neurogenesis, neurotransmitter, glucocorticoid, and circadian rhythm pathways; EML in repressed transcriptional regions correlated with faster age acceleration.

Conclusions:

• The accumulation of SEMs, measured by EML, is associated with accelerated epigenetic aging.
• Specific biological pathways and genomic regions may contribute to epigenetic mutation accumulation and aging.
• Findings suggest a role for epigenetic mutations in the aging process.