Removing the ovaries did not accelerate biological age based on chemical marks on DNA in rat experiments

Removing the ovaries did not accelerate biological age based on chemical marks on DNA in rat experiments

In a preprint published on August 26, the authors compared two explanations for the association between menopause and biological age. Removing the ovaries did not alter epigenetic age acceleration in rats. In women, the clocks ran faster among those whose final menstrual period occurred earlier. The authors consider the timing of menopause a potential marker of biological aging.

Epigenetic clocks estimate biological age from chemical marks on DNA. When this estimate exceeds the age expected from chronological age, the difference is described as epigenetic age acceleration. A 2016 study combining four large observational studies found that an earlier age at the final menstrual period and the surgical removal of both ovaries were associated with greater epigenetic age acceleration. The direction of this association remained uncertain. Loss of ovarian function might itself accelerate the clocks, or early menopause and epigenetic age acceleration might both result from a shared aging process.

The new preprint tests these explanations in rats. In two experiments, the researchers compared animals that underwent removal of both ovaries, the same procedure followed by administration of estradiol, one of the main estrogens, or a sham operation. They found no differences between the groups in epigenetic age or epigenetic age acceleration in the tissues examined.

The authors also studied natural reproductive aging without surgery. They divided rats of the same age according to whether their cycles were regular, irregular, or had ceased. They again found no differences between these groups in the liver. All animals were the same age.

The association persisted in women. The authors conducted a single cross-sectional comparison of blood cells from women whose final menstrual period occurred before 50 years of age, which was earlier than the median for participants in this group, and from women whose final menstrual period occurred later. The earlier group had greater epigenetic age acceleration according to several calculation methods.

The rat experiments tested whether loss of ovarian function is sufficient by itself to accelerate epigenetic clocks. The comparison in women confirmed the association between earlier menopause and greater epigenetic age acceleration. The authors therefore propose that the timing of menopause may serve as a marker of a broader trajectory of biological aging.