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Developmental Biology - Menopause

Ahhh Menopause!

Association found between late onset menopause and a longer life...


If you're wondering why you entered menopause earlier or later than other women, blame your mother.

This is because numerous studies have confirmed the role of genetics in determining a woman's age at menopause. A new study not only reconfirms this association but additionally suggests a link to familial longevity. Results of the study are published online in Menopause, the journal of The North American Menopause Society (NAMS).
The age of menopause is clinically defined as one year after the final menstrual period ends, on average about 52 years. However, every year thousands of women outperform this statistic by entering menopause later in life, whereas many others naturally enter menopause much earlier.

Although menopause can occur earlier as the result of various conditions such as smoking, chemotherapy, and an elevated body mass index, the age of menopause is generally accepted to be most influenced by family history. So, if your mother experienced her menopause early, chances are you will also begin the transition earlier in life.

The goal of this latest study, focused on reproductive life, was to identify genetic variants associated with the delayed age of menopause based on familial longevity. Results were based on a meta-analysis of several larger studies, including the Long Life Family Study, the Health and Retirement Study, and the Framingham Heart Study.
These studies found women who were able to have children beyond the age of 40 years were four times more likely than average women of living to 100 years or older. Women who had children at age 35 years or older were 1.5 times more likely to live past 100 years.

In this study, researchers performed a meta-analysis for possible genetic variants associated with age of menopause in those women who ultimately lived to a very old age. The findings provided more evidence for a genetic basis for age of menopause beginning — and suggest there may be genetic mechanisms of age of menopause linked to human longevity.
"Genetic variants associated with late menopause have been found to be associated with longer life. Although early menarche and total number of reproductive years have not been associated with slower aging, late menopause (long reproductive potential) appears associated with slower aging."

JoAnn Pinkerton MD, Fellow - American Congress of Obstetricians and Gynecologists; Professor, Obstetrics, University of Virginia; Executive Director, North American Menopause Society (NAMS).

Abstract
Objective
We hypothesize that mechanisms associated with extended reproductive age may overlap with mechanisms for the selection of genetic variants that slow aging and decrease risk for age-related diseases. Therefore, the goal of this analysis is to search for genetic variants associated with delayed age of menopause (AOM) among women in a study of familial longevity.

Methods
We performed a meta-analysis of genome-wide association studies for AOM in 1,286 women in the Long Life Family Study (LLFS) and 3,151 women in the Health and Retirement Study, and then sought replication in the Framingham Heart Study (FHS). We used Cox proportional hazard regression of AOM to account for censoring, with a robust variance estimator to adjust for within familial relations.

Results
In the meta-analysis, a single nucleotide polymorphism (SNP) previously associated with AOM reached genome-wide significance (rs16991615; HR = 0.74, P = 6.99 × 10-12). A total of 35 variants reached >10-4 level of significance and replicated in the FHS and in a 2015 large meta-analysis (ReproGen Consortium). We also identified several novel SNPs associated with AOM including rs3094005: MICB, rs13196892: TXNDC5 | MUTED, rs72774935: SSBP2 | ATG10, rs9447453: COL12A1, rs114298934: FHL2 | NCK2, rs6467223: TNPO3, rs9666274 and rs10766593: NAV2, and rs7281846: HSPA13.

Conclusions
This work indicates novel associations and replicates known associations between genetic variants and AOM. A number of these associations make sense for their roles in aging.

Video Summary
Supplemental Digital Content 1, http://links.lww.com/MENO/A420.

Authors
Rebecca S. Moore, Rachel Kaletsky and Coleen T. Murphy.>


Acknowledgements
The authors thank all the nurses and all the parents and babies who participated in this study; and the Division of ENT, the Plateforme de Recherche de Pediatrie, and the Centre for Biomedical Imaging of the University Hospital of Geneva for their support. The authors declare no competing interests. This study was supported by grants from the Swiss National Science Foundation (32473B_135817/1), the foundation Prim’enfance, and European Union’s Horizon 2020 research and innovation programme under Grant Agreement 666992.

Founded in 1989, The North American Menopause Society (NAMS) is North America's leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field — including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education — makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit http://www.menopause.org.

About MUSC
Founded in 1824 in Charleston, MUSC is the oldest medical school in the South, as well as the state's only integrated, academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and 700 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2018, MUSC set a new high, bringing in more than $276.5 million. For information on academic programs, visit http://musc.edu.

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Jun 14 2019   Fetal Timeline   Maternal Timeline   News  




Extended reproductive age may overlap with select gene variantions that slow aging,
perhaps genes which even decrease risk for age-related diseases. This new analysis
searched for genes associated with delayed age for menopause onset - based on
3 longitudinal studies of familial longevity. Image CREDIT GIPHY.com.


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