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Abstract
To investigate associations between the age of menopause and the DNA methylation levels of two repetitive elements, Alu and LINE-1, we performed plasma DNA extraction on 161 subjects and serum cell-free DNA extraction on 120 subjects. We grouped women by menopausal age as follows: ≤ 48 years (earlier menopause), ≥ 52 years (later menopause), and 48-52 years (control). The DNA methylation levels of Alu and LINE-1 were measured by MethyLight PCR. The results showed that the DNA methylation levels of both Alu and LINE-1 were inversely correlated with menopausal age in the plasma DNA cohort (r = 0.079, P < 0.001 for Alu; r = 0.045, P = 0.007 for LINE-1) as well as in the serum DNA cohort (r = 0.087, P = 0.001 for Alu; r = 0.041, P = 0.026 for LINE-1). Alu methylation levels in both the plasma and serum DNA cohorts and LINE-1 methylation levels in the plasma cohort were remarkably higher in the earlier menopause group than in the later menopause and control groups (P < 0.01 and P < 0.05, respectively). In the serum DNA cohort, the LINE-1 methylation levels in the later menopause group were significantly lower than that in the earlier menopause group and control group (P < 0.05). Therefore, methylation levels of Alu and LINE-1 were significantly associated with menopausal age. Women with earlier menopause showed hypermethylation in both repetitive elements, while women with later menopause showed hypomethylation. These findings suggest that altered DNA methylation in leukocytes and serum cell-free DNA may represent a biomarker of menopausal age.
Highlights
Perls’s study found that individuals from families with a history of longevity tended to exhibit delayed reproductive aging [5]
The DNA methylation levels of both Alu and LINE-1 were inversely correlated with menopausal age in the plasma DNA cohort (r = 0.079, P < 0.001 for Alu; r = 0.045, P = 0.007 for LINE-1) (Fig. 1A and B) as well as in the serum DNA cohort (r = 0.087, P = 0.001 for Alu; r = 0.041, P = 0.026 for LINE-1) (Fig. 1C and D)
Correlation between Alu and LINE-1 methylation. Because both Alu and LINE-1 were demethylated with menopausal age, we evaluated the correlations of methylation levels between Alu and LINE-1
Summary
Perls’s study found that individuals from families with a history of longevity tended to exhibit delayed reproductive aging [5]. These studies suggest that there might be a relationship between menopause age and biological aging rate, and that menopausal age is considered to be heritable. The association between DNA methylation levels and menopausal age has not been well investigated. Hypomethylation of Alu but not LINE-1 has been reported as a global event in aging cells [16]. We aimed to investigate associations between menopausal age and the DNA methylation levels of two repetitive elements, Alu and LINE-1, in blood.
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