It is well known that the health of women and aspects of aging worsen in many ways after menopause. The biochemistry of menopause and its role in aging is not as easily researched as it might be, as mice do not naturally exhibit menopause. Menopause can certainly be induced by chemical or surgical means in mice, but these models are all artificial and come with caveats as to the interpretation of results. It was thought that only a few larger mammals exhibit menopause, and this remains the consensus, but in recent years researchers have provided evidence to suggest that most large mammals do in fact undergo menopause. Identifying that this is the case has not been an area of focus, as large mammals are not often used in fundamental research into mechanisms of aging for reasons of cost and time.
In today’s open access paper, researchers use an aging clock to assess biological age in women at various stages of menopause. The usual concerns apply for the use of clocks, as to whether they are in fact a good representation of of the accumulated damage and dysfunction of aging in any novel specific context. The only way to determine whether this is the case is to accumulate as much data as possible in many contexts, so researchers here use a well-established clock, one for which there is plenty of existing data to support its ability to measure something useful in this context. Setting that aside, the results are much as one would expect, and show that both entering menopause and undergoing earlier menopause both correlate with an increased biological age.
This study aimed to investigate the associations between menopausal factors and both comprehensive and organ-specific biological aging, as well as the modifying role of reproductive history. This study included 37,244 women from the China Multi-Ethnic Cohort (CMEC) and 140,479 from the UK Biobank (UKB). Menopausal factors included menopausal status, menopausal transition, and age at menopause. Comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera-Doubal method and clinical biomarkers and have been shown to predict age-related health outcomes. Multiple linear regression and change-to-change models were applied, with stratified analyses based on reproductive history.
Compared with pre-menopausal women, those who were peri-menopausal or post-menopausal or had undergone hysterectomy or oophorectomy exhibited greater acceleration in comprehensive, liver, metabolic, and kidney BA. In longitudinal change-to-change models, women undergoing menopausal transition showed greater increases in comprehensive BA (CMEC: β = 1.33; UKB: β = 2.60), as well as liver, metabolic, and kidney BAs compared to those remaining pre-menopausal. Earlier age at menopause was associated with accelerated comprehensive BA in UKB (earlier than 40 years: β = 0.69; 40-44 years: β = 0.24). Across organ-specific BAs, liver BA showed the strongest associations with menopausal factors. Reproductive history like age at live birth and number of live births emerged as potential modifiers of these associations.
Menopause, particularly the menopausal transition, was associated with accelerated comprehensive and organ-specific biological aging, with liver aging being most affected. These findings underscore the menopausal transition as a critical window for interventions to enhance women’s health and longevity.
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