על אודות
Genetics of female and male reproductive traits and their relationship with health, longevity and consequences for offspring While previous research has focused on female reproductive health, the study reviews what is known about the genetics of male fertility. Understanding these genetic links is critical as more people choose to delay having children, making reproductive health and ageing even more intertwined. The review explored the connections between reproductive genes and longevity, finding that genes like ESR1 (estrogen receptor 1) are linked to reproductive traits as well as to cancer risk.
The neuroprotective and life-prolonging function of sirtuins is the main direction of research. However, theories regarding the usefulness of sirtuins as longevity enzymes are not unambiguous. As mentioned earlier, sirtuins regulate many biological processes due to their high substrate specificity and impact on numerous factors. Sirtuins are also responsible for women’s gynecological health because they regulate ovarian function on many levels. As mentioned, sirtuins are involved in metabolic control and epigenetic modification .
Out of the metabolic traits, our T2D results that are in line with clinical trials but contrast recent genetic findings23,33,76 merit an extended discussion. In addition, all these traits correlate with obesity32, that in turn correlates with PCOS and T levels (Supplementary Fig. 10 and Supplementary Data 8), and we may have not been able to fully account for such confounding. We further estimate that normal heritable variation in T levels—contrary to popular beliefs—has only modest effects on many phenotypes. Accordingly, we stress the complex relationship of T levels with many metabolic and endocrine traits. Whereas our analyses supported causality of genetically determined T, e.g., to hormone-sensitive cancers and hirsutism, this did not apply for traits such as obesity, T2D or hypothyroidism. We observed significant genetic correlations to hormonal cancers in both sexes, as expected23,26.
However, there is no reason to think that genetics are susceptible to cohort effects in the UK Biobank. Although this study used an innovative approach to generate an unbiased assessment of the effect of testosterone on survival, it has several limitations. The first-line treatment for diabetes, metformin, may reduce testosterone in women58, but not men59.
Carefullycontrolled large-scale studies are needed to determine whether testosterone’spleiotropic effects are of benefit or harm to healthy aging and longevity. Thus, as women tend tolive longer, they are more susceptible to age-related health problems and in particular todeclines in muscle mass (8) when compared with men.However, whether there are positive relationships between age-related loss of sex hormones,declines in muscle mass, and physical function versus longevity has not been studied. In this study we combined data from over 625,000 participants of the FinnGen and UK Biobank cohorts to provide a broad and systematic perspective into the function of long term T exposure, a heritable trait in both sexes that can be proxied by using genetic data, as a regulator of health and disease in men and women. To study the impacts of T and SHBG levels in datasets where these measurements are not directly available, we next constructed sex-specific genetic predictors, PGSs, for each trait applying the LDpred algorithm39 to the sex-specific GWASs.
