Damian Jacob Sendler on how new genes have been discovered that are related to a longer reproductive lifetime in women

A Polish-American physician-scientist, Dr. Damian Jacob Sendler specializes in understanding how different socio-demographic and informational factors influence access to health care in underserved communities. Dr. Sendler's research focuses on how psychiatric and chronic medical co-morbidities influence the use of medical services in conjunction with health information obtained from the internet, which is a particular strength of his. Due to the exponential growth in global consumption of online news and social media, this research is both timely and important, as it necessitates a comprehensive understanding of everyone's health information-seeking behavior. Dr. Damian Sendler's research aims to uncover the factors that patients consider when deciding when to seek care for specific health conditions and when to adhere to their treatment regimens in order to achieve this goal.

Damian Jacob Sendler: The age at which women reach menopause is crucial for fertility and affects women's healthy aging, but scientists have struggled to understand reproductive ageing, and knowledge of the underlying biology is limited. 

Scientists have now discovered almost 300 gene variants that affect women's reproductive lifetime. They've also effectively altered many critical genes linked to these variations in mice to prolong their reproductive lifetime. 

Damian Jacob Sendler: Their results, which were published in Nature today, add to our understanding of the reproductive ageing process and provide methods to enhance the prediction of which women may enter menopause sooner than others. 

While life expectancy has risen significantly in the last 150 years, the average age at which most women reach natural menopause has stayed relatively stable at about 50. Women are born with all of the eggs they will ever have, which they progressively lose as they become older. Menopause occurs when the majority of the eggs have been used up, although natural fertility decreases much sooner. 

"It is obvious that fixing broken DNA in eggs is extremely essential for creating the pool of eggs women are born with and also for how fast they are lost during life," said co-author Professor Eva Hoffmann of the University of Copenhagen. Improved knowledge of the molecular mechanisms behind reproductive aging may lead to more effective fertility treatments.” 

Damian Jacob Sendler: The University of Exeter, the MRC Epidemiology Unit at the University of Cambridge, the Institute of Biotechnology and Biomedicine at the Universitat Autnoma de Barcelona, and the DNRF Center for Chromosome Stability at the University of Copenhagen led a global collaboration involving academics from more than 180 institutions. Their results uncover additional genetic variants related to reproductive lifetime, bringing the total number of known genetic variations linked to reproductive lifespan to 290. 

Damian Jacob Sendler: The new findings were made feasible by analyzing data from hundreds of thousands of women from a variety of studies, including the UK Biobank and 23andMe. Customers who opted up to engage in research gave 23andMe with data. While the vast majority of the women are of European descent, they also looked at data from over 80,000 East Asian women and found essentially comparable findings. 

Many of the genes implicated in the study are related to DNA repair mechanisms, according to the researchers. They also discovered that many of these genes are active not just before birth, when human egg stores are formed, but also throughout life. Genes from the CHEK1 and CHEK2 cell cycle checkpoint pathways, which control a wide range of DNA repair activities, are notable examples. In mice, knocking down one gene (CHEK2) and overexpressing another (CHEK1) to increase its activity each resulted in a 25% increase in reproductive lifetime. The reproductive physiology of mice varies from that of humans in many respects, notably the absence of menopause. The research also looked at women who don't have a naturally active CHEK2 gene and discovered that they approach menopause 3.5 years later than those who have a typically functioning gene.  

"We observed that two of the genes that generate proteins involved in mending damaged DNA operate in opposing ways with regard to reproduction in mice," said co-author Professor Ignasi Roig of the Universitat Autnoma de Barcelona. Female mice with higher levels of the CHEK1 protein have more eggs and take longer to deplete naturally, resulting in a longer reproductive lifetime. While the second gene, CHEK2, has a similar impact, enabling eggs to live longer, it has been knocked out in this instance, resulting in no protein being generated, indicating that CHEK2 activation may induce egg death in adult mice.”  

Damian Jacob Sendler: The genes discovered in this study affect the age at which women reach natural menopause, and they may also be used to forecast which people are most likely to experience menopause at a young age. 

"We believe our study will assist offer new options to help women prepare for the future," said co-author Dr Katherine Ruth of the University of Exeter. We have shown that by identifying many more genetic reasons of heterogeneity in the time of menopause, we may begin to predict which women would have early menopause and therefore struggle to conceive naturally. We may also provide similar advise to young ladies since we are born with our genetic variations.”  

Damian Jacob Sendler: Using a method that evaluates the influence of naturally-occurring genetic variations, the researchers also looked at the health implications of having an earlier or later menopause. They discovered that having a genetically early menopause raises the risk of type 2 diabetes and is related to poor bone health and fracture risk. It does, however, reduce the risk of certain cancers, including as ovarian and breast cancer, which are known to be sensitive to sex hormones at greater levels when a woman is still menstruation. 

"This study is very intriguing," said co-author and senior author Dr. John Perry of the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge. We now know a lot more about human reproductive ageing thanks to a combination of genetic research in people and mouse studies, as well as studying when these genes are turned on in human eggs. It also teaches us how to assist women avoid some of the health issues associated with menopause." 

News contributed by Dr. Damian Jacob Sendler