Repetitive Element DNA Methylation is Associated with Menopausal Age

Area of Science:

• Epigenetics
• Reproductive Endocrinology
• Molecular Biology

Background:

• Menopause is a significant biological transition.
• DNA methylation patterns can change with age and reproductive status.
• Repetitive elements like Alu and LINE-1 are abundant in the genome and their methylation is dynamic.

Purpose of the Study:

• To investigate the association between menopausal age and DNA methylation levels of Alu and LINE-1 repetitive elements.
• To determine if plasma and serum cell-free DNA methylation can serve as biomarkers for menopausal age.

Main Methods:

• Plasma and serum cell-free DNA were extracted from 161 and 120 subjects, respectively.
• Subjects were grouped by menopausal age: ≤48 years (earlier), ≥52 years (later), and 48-52 years (control).
• DNA methylation levels of Alu and LINE-1 were quantified using MethyLight PCR.

Main Results:

• DNA methylation levels of both Alu and LINE-1 were inversely correlated with menopausal age in both plasma and serum DNA cohorts.
• Earlier menopause groups exhibited significantly higher Alu and LINE-1 methylation compared to later menopause and control groups.
• Later menopause groups showed significantly lower LINE-1 methylation in serum DNA compared to earlier menopause and control groups.

Conclusions:

• DNA methylation levels of Alu and LINE-1 are significantly associated with menopausal age.
• Altered DNA methylation, specifically hypermethylation in earlier menopause and hypomethylation in later menopause, is observed.
• These findings suggest that DNA methylation in leukocytes and serum cell-free DNA may be a potential biomarker for menopausal age.