Alu hypomethylation in naturally and surgically postmenopausal women; a cross-sectional study

Menopause, which may accelerate the hallmarks of the natural aging process, represents a point in time characterized by the permanent cessation of menstruation following the loss of ovarian estrogen production. Unlike natural menopause, which is characterized by a gradual decrease in estrogen production, when both ovaries are removed before the natural age of menopause, the onset of estrogen deprivation is abrupt. Further, a decrease in genome methylation frequently occurs in aging cells, and the major interspersed repetitive DNA elements in humans are Alu elements. In blood cells, Alu demethylation starts at an age of approximately 40 years, and increases with age. Here, we explored the Alu methylation levels corresponding to age-matched pre-menopausal, naturally postmenopausal, and surgically postmenopausal women aged 45-55 years (n = 60 in each group). Our results indicated that the body mass index (BMI), time-since-menopause, and Alu methylation levels corresponding to the three groups were significantly different. However, no correlations between Alu methylation level and BMI, time-since-menopause, or age were observed. Additionally, the Alu methylation level corresponding to the natural post-menopause group was significantly lower those corresponding to the pre-menopausal (p = 0.001) and surgical post-menopausal (p = 0.037) groups. In conclusion, Alu hypomethylation occurs in naturally postmenopausal women, implying that when women reach the age of natural menopause, the cell aging process may progress significantly with genome hypomethylation. These findings, notwithstanding, further studies are necessary to clarify whether bilateral oophorectomy before the age of menopause affects the cell aging process to a greater extent than natural menopause, and whether estrogen therapy or other interventions can delay cell aging in this regard.