Menopause makes women ‘older’

The earlier a woman enters the menopause, the faster she is likely to age, at least in biological terms, says Prof. Steve Horvath of the University of California.

Human reproductive senescence (most obviously manifested in the menopause) has frequently been associated with aging but, until now, no-one has fully explained the link. This is partly due to the difficulty quantifying biological age. However, recent studies have shown that a phenomenon known as ‘DNA methylation’ – the number of methyl (CH3) groups attached to a cell’s DNA – correlates with age. Methylation, which renders genes inactive, is one of a number of so-called ‘epigenetic’ mechanisms controlling how genes act.

Writing in PNAS, Steve Horvath of the University of California, Los Angeles, and colleagues, describe how they used a DNA methylation-based technique dubbed the ‘epigenetic clock’ to assess the age of three tissues – blood, saliva, and cells from inside the cheek. They compared these measures with the age at menopause of over 3,000 women from across the world.

Their key finding was a correlation between the timing of menopause and the rate at which blood DNA ages. That is, women who experience a late menopause tend to be biologically ‘younger’ than those for whom it comes early. This was further supported by identifying specific DNA sites associated with both age at menopause and epigenetic age in blood. Strangely, the same correlation was not found with the saliva and cheek cells, a discrepancy the authors attribute to differential rates of aging in tissues under different stresses within individuals.

Excitingly, Horvath’s team also found evidence of a possible causal relationship: going through the menopause – even if surgically-induced – itself appears to accelerate epigenetic aging. Although the authors are quick to point out that further work is needed to dissect this cause-and-effect relationship, the potential implications are clear. Horvath agrees: “it would be very interesting to explore the utility of different types of hormone treatments [to slow aging].”

He goes on, “DNA methylation biomarkers are revolutionizing our understanding of human aging” Although we don’t know exactly how epigenetic changes impact on our bodies, “we do know that the epigenetic clock and similar biomarkers are predictive of all-cause mortality [i.e., life expectancy]” Although not very informative for individuals, he says, “the results are statistically significant once you analyze a large cohort of people.” And are these effects limited to women? No, says Horvath, “It would be fascinating to evaluate the effect of testosterone treatment on the epigenetic age of organs in men. Somebody ought to look at this question.” [393]


  1. Levine, M.E., Lu, A.T., Chen, B.H., Hernandez, D.G., Singleton, A.B., et al. (2016). Menopause accelerates biological aging. Proceedings of the National Academy of Science of the United States of America 113(33): 9327-9332.

Author: Alexandra Davey

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