Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts

Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.

Divergent Trends of Lifespan Variation During Mortality Crises

Lifespan variation has been attracting increasingly greater attention as a measure of population health and mortality. Several studies have analysed periods of steady mortality decline, highlighting a strong inverse relationship between lifespan variation and life expectancy. Recent research has found that this association weakens, and even reverses, when mortality does not improve equally over age. However, to date no study has comprehensively explored the behaviour of lifespan variation when mortality increases significantly. Analysing three epidemics and two famines in Europe from the eighteenth to the twentieth centuries, we find that, during these events, relative lifespan variation increases, while absolute variation declines, and that subsequently both quickly revert to pre-crisis levels. Using decomposition techniques, we show that mortality at older ages leads to a temporary increase in absolute – but not relative – variation. Moreover, female lifespan variation is less affected by the crises than that of males, because of the higher impact of infant and child mortality on male lifespan variation. By underlining different trends of lifespan variation by sex and indicator, we offer new insight into the consequences of mortality crises. Contrary to what is often asserted, we also show that the choice of lifespan variation indicator is not always inconsequential.

A Stresipteran parasite extends the lifespan of workers in a social wasp

In social wasps, female lifespan depends on caste and colony tasks: workers usually live a few weeks while queens as long as 1 year. Polistes dominula paper wasps infected by the strepsipteran parasite Xenos vesparum avoid all colony tasks, cluster on vegetation where parasite dispersal and mating occur, hibernate and infect the next generation of wasp larvae. Here, we compared the survival rate of infected and uninfected wasp workers. Workers’ survival was significantly affected by parasite sex: two-third of workers parasitized by a X. vesparum female survived and overwintered like future queens did, while all workers infected by a X. vesparum male died during the summer, like uninfected workers that we used as controls. We measured a set of host and parasite traits possibly associated with the observed lifespan extension. Infected overwintering workers had larger fat bodies than infected workers that died in the summer, but they had similar body size and ovary development. Furthermore, we recorded a positive correlation between parasite and host body sizes. We hypothesize that the manipulation of worker’s longevity operated by X. vesparum enhances parasite’s fitness: if workers infected by a female overwinter, they can spread infective parasite larvae in the spring like parasitized gynes do, thus contributing to parasite transmission.

Stretched Exponential Survival Analysis for South Korean Females

South Korea has recently exhibited a remarkable rapid increase in female lifespan. Here, a mathematical analysis is suggested for a clear interpretation of current trends in female lifespan in South Korea. To mathematically analyze life tables, a modified stretched exponential function is employed and demonstrated to estimate current trends of female lifespan in South Korea based on reliable life tables from 1987 to 2016 taken from the Korean Statistical Information Service. This methodology enables us to perform quantitative and comparative analyses of female lifespan in South Korea with representative industrialized countries such as Japan, France, Australia, Switzerland, UK, Sweden, and USA. This analysis provides quantitative and comparative evidence that South Korea has the highest increase rate of female lifespan over the past three decades. Further application would be feasible for a better estimation of human aging statistics.

Ras inhibition by trametinib treatment in Drosophila attenuates gut pathology in females and extends lifespan in both sexes

Females of most species live longer than do males. Furthermore, lifespan-extending interventions in laboratory model organisms are often more effective in females (Regan and Partridge 2013). For instance, genetic and pharmacological suppression of activity of the insulin/insulin-like signalling - target of rapamycin (IIS-TOR) network generally extends female lifespan more than that of males in both Drosophila and mice (Clancy et al. 2001; Selman et al. 2009). We previously showed that attenuation of Ras-dependent IIS signalling by treatment with the FDA-approved MEK inhibitor, trametinib extends lifespan in females (Slack et al. 2015). Here, we demonstrate that trametinib treatment has beneficial effects on female-specific, age-related gut pathologies, similar to those obtained through dietary restriction (Regan et al. 2016). Importantly, we identify Ras inhibition as an effective lifespan-extending manipulation in males as well as females, pointing to parallel mechanisms of lifespan extension by trametinib in both sexes.

Trends in female lifespan in South Korea, 1987–2016

South Korea shows a remarkable rapid increase in lifespan in recent decades. Employing a mathematical model that is appropriate for human survival curves, we evaluate current trends in female lifespan for South Korea over three recent decades, 1987–2016, and predict coming trends in female lifespan until 2030. From comparative analyses with industrialized countries such as Japan, France, Australia, Switzerland, UK, Sweden, and USA, we confirm that South Korea has the highest increase rate of female lifespan in recent decades, and estimate that maximum lifespan would reach 125 years and characteristic life would surpass 95 years for South Korean female by 2030. South Korea would deserve much attention in study on human health and longevity as the longest-lived country in coming decades.