Sex-specific differences in liver DNA methylation patterns and epigenetic aging in mice

Area of Science:

• Epigenetics
• Genomics
• Aging Research

Background:

• Biological sex influences aging, disease susceptibility, and lifespan.
• DNA methylation patterns serve as a quantitative marker for biological aging.
• Investigating sex-specific differences in epigenetic aging is crucial for understanding age-related health disparities.

Purpose of the Study:

• To determine if aged male and female mice exhibit distinct liver DNA methylation patterns.
• To assess sex-specific differences in epigenetic aging using DNA methylation data.
• To identify specific genes and CpG sites associated with sex-based methylation variations in aging livers.

Main Methods:

• Liver DNA methylation analysis in aged C57BL/6 mice (6 males, 11 females).
• Estimation of biological age (DNAge®) using a DNA methylation predictor.
• Comparison of site-specific methylation, biological age acceleration (ΔDNAge®), and principal component analysis (PCA) between sexes.

Main Results:

• Twelve CpG sites across six genes (Fam84b, Zswim6, Hsf4, Mn1, Qprt, Rapgefl1) displayed significant sex-associated methylation differences.
• Fam84b showed the most consistent sex-associated effect, with higher methylation in males.
• No significant sex differences were observed in overall biological age (DNAge®) or age acceleration (ΔDNAge®).

Conclusions:

• Aged mice exhibit sex-specific liver DNA methylation patterns, distinct from younger mice.
• While overall epigenetic age did not differ by sex, sex-dependent epigenetic changes may develop later in life.
• These findings suggest potential sexual dimorphism in age-related liver function influenced by epigenetic modifications.