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Published on: April 7, 2014
Early menopause results from instead of causes premature general ageing
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, The Netherlands.
Abstract:
Recent genome-wide association studies have shown that the majority of genes involved in menopause are also instrumental in double-strand break repair and mismatch and base excision repair of DNA. Cumulative DNA damage causes cellular senescence resulting in exhaustion of somatic cell renewal capacity and cellular dysfunction, and eventually to accelerated cell death, generally called ageing. A similar erosion of the genome occurs within the germ cell line and thus in the ovaries. Subsequently, the systemic 'survival' response intentionally suppresses the sex-steroid hormone output, which in turn may contribute to the onset of menopause. The latter occurs in particular when age-dependent DNA damage accumulates. Both effects are expected to synergize to promote ovarian silencing resulting in menopause. Consequently, ageing of the soma seems to be a primary driver for the loss of ovarian function in women. Therefore menopause is the result rather than the cause of ageing.
Insights
Menopause is driven by DNA damage accumulation and cellular aging, not the other way around. This aging process erodes ovarian function, leading to menopause as a consequence of somatic aging.
Area of Science:
- Genetics
- Molecular Biology
- Gerontology
Background:
- Genome-wide association studies link menopause genes to DNA repair pathways.
- Accumulated DNA damage drives cellular senescence and organismal aging.
- Genomic erosion also affects the female germline, impacting ovarian function.
Purpose of the Study:
- To investigate the relationship between DNA damage, aging, and the onset of menopause.
- To propose a new model where somatic aging drives ovarian decline and menopause.
Main Methods:
- Review of recent genome-wide association studies.
- Analysis of the interplay between DNA repair mechanisms, cellular senescence, and reproductive aging.
- Integration of genetic and cellular aging concepts.
Main Results:
- Genes involved in menopause are critical for DNA repair (double-strand break, mismatch, base excision).
- Cumulative DNA damage leads to cellular senescence, dysfunction, and accelerated aging.
- Ovarian aging, driven by genomic erosion, triggers a systemic survival response that suppresses sex-steroid hormones, contributing to menopause.
Conclusions:
- Somatic aging, characterized by DNA damage accumulation, is a primary driver of ovarian function loss.
- Menopause is presented as a result, not a cause, of the aging process.
- This perspective reframes menopause as an outcome of fundamental aging mechanisms.
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