Early menopause results from instead of causes premature general ageing

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.