Menopause: Genome stability as new paradigm.
Menopause is defined as the age-dependent permanent cessation of menstruation and ovulation due to ovarian failure. Menopause occurs on average around the age of 51 years. Recent genome-wide association studies (GWAS) have identified over 44 genetic variants that are associated with age of onset of natural menopause. Genes linked with menopause can be classified into three major groups: genes implicated in genome stability (DNA repair), immune function and mitochondrial biogenesis. Biological and epidemiological data indicate that reproductive performance, age at menopause and longevity are interlinked through common genetic factors, which play a pivotal role in DNA repair and genome maintenance, which has been linked before with the process of ageing. Consequently, ageing of the soma as a result of inefficient DNA repair appears also to be responsible for failure to reproduce and the subsequent occurrence of menopause. In this way reproductive performance may be strongly linked to the physical condition of the soma and may be a very good predictor of general health in later life.
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands. Electronic address: j.laven@erasmusmc.nl.
Joop S E
JSE
Laven
Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands.
Jenny A
JA
Visser
Human Genotyping Facility, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands.
Andre G
AG
Uitterlinden
Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands.
Wilbert P
WP
Vermeij
Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands.
Jan H J
JHJ
Hoeijmakers
D000375:Aging / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D006801:Humans; D008593:Menopause / Q000235:genetics*; D012098:Reproduction
DNA repair and maintenance; GWAS; Genetics; Health risks; Menopause; New paradigm