Menopause accelerates biological aging

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further

Using Recruiting Rankings And Returning Team Measurements To Predict College Football Team Success

This paper proposes and compares a set of models of college football team performance for teams in major conferences during the years of 2006 – 2018. The outcome measure of team performance is the team’s standardized Sagarin Ranking at the end of the season after the postseason bowl games and, in recent years, playoff games are complete. Potential predictor variables include several variables taken from the team recruiting rankings at the website www.rivals.com, and other attributes of the team compiled from an annual college football prediction magazine. Models considered include models screened via traditional forward, backward, and stepwise model selection methods, as well as a regression tree model. These candidate models are first compared using a cross-validation technique where each individual season is used successively as a test data set, and the predictive accuracy of the candidate models are compared after these successive comparisons. We find that the model chosen via stepwise selection performs the best in this cross-validation comparison but that other models have comparable error rates. We further consider refinements of the forward selection model when quadratic terms and a piecewise approach is taken for two predictors, and compare the prediction error rates for these models using the same cross-validation technique. Our findings from these analyses suggest that teams with higher recruiting rankings are predicted to perform better in a given season, but that other factors about the team are also significant predictors of performance

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

A new perspective of the climatological features of upper-level cut-off lows in the Southern Hemisphere

This study presents a detailed view of the seasonal variability of upper-level cut-off lows (COLs) in the Southern Hemisphere. The COLs are identified and tracked using data from a 36-year period of the European Centre for Medium Range Weather Forecast reanalysis (ERA-Interim). The objective identification of the COLs uses a new approach, which is based on 300 hPa relative vorticity minima, and three restrictive criteria of the presence of a cold-core, stratospheric potential vorticity intrusion, and cut-off cyclonic circulation. The highest COL activity is in agreement with previous studies, located near three main continental areas (Australia, South America, and Africa), with maximum frequencies usually observed in the austral autumn. The COL mean intensity values show a marked seasonal and spatial variation, with maximum (minimum) values during the austral winter (summer), a unique feature that has not been observed previously in studies based on the geopotential. The link between intensity and lysis is examined, and finds that weaker systems are more susceptible to lysis in the vicinity of the Andes Cordillera, associated with the topographic Rossby wave. Lysis and genesis regions are close to each other, confirming that COLs are quasi-stationary systems. Also, COLs tend to move eastward and are faster over the higher latitudes. The mean growth/decay rates coincide with the major genesis and lysis density regions, such as the significant decay values across the Andes all year. As a consequence of using vorticity for the tracking method a longer lifetime of COLs is detected than in other studies, but this does not affect the total frequency of occurrence. Comparisons with other studies suggest that the differences in seasonality are due to uncertainties in the reanalyses and the methods used to identify COLs

Madagascar corals track sea surface temperature variability in the Agulhas Current core region over the past 334 years

The Agulhas Current (AC) is the strongest western boundary current in the Southern Hemisphere and is key for weather and climate patterns, both regionally and globally. Its heat transfer into both the midlatitude South Indian Ocean and South Atlantic is of global significance. A new composite coral record (Ifaty and Tulear massive Porites corals), is linked to historical AC sea surface temperature (SST) instrumental data, showing robust correlations. The composite coral SST data start in 1660 and comprise 200 years more than the AC instrumental record. Numerical modelling exhibits that this new coral derived SST record is representative for the wider core region of the AC. AC SSTs variabilities show distinct cooling through the Little Ice Age and warming during the late 18th, 19th and 20th century, with significant decadal variability superimposed. Furthermore, the AC SSTs are teleconnected with the broad southern Indian and Atlantic Oceans, showing that the AC system is pivotal for inter-ocean heat exchange south of Africa

Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio

Frequency of extreme Sahelian storms tripled since 1982 in satellite observations

The hydrological cycle is expected to intensify under global warming, with studies reporting more frequent extreme rain events in many regions of the world, and predicting increases in future flood frequency. Such early, predominantly mid-latitude observations are essential because of shortcomings within climate models in their depiction of convective rainfall. A globally important group of intense storms—mesoscale convective systems (MCSs)—poses a particular challenge, because they organize dynamically on spatial scales that cannot be resolved by conventional climate models. Here, we use 35 years of satellite observations from the West African Sahel to reveal a persistent increase in the frequency of the most intense MCSs. Sahelian storms are some of the most powerful on the planet, and rain gauges in this region have recorded a rise in ‘extreme’ daily rainfall totals. We find that intense MCS frequency is only weakly related to the multidecadal recovery of Sahel annual rainfall, but is highly correlated with global land temperatures. Analysis of trends across Africa reveals that MCS intensification is limited to a narrow band south of the Sahara desert. During this period, wet-season Sahelian temperatures have not risen, ruling out the possibility that rainfall has intensified in response to locally warmer conditions. On the other hand, the meridional temperature gradient spanning the Sahel has increased in recent decades, consistent with anthropogenic forcing driving enhanced Saharan warming. We argue that Saharan warming intensifies convection within Sahelian MCSs through increased wind shear and changes to the Saharan air layer. The meridional gradient is projected to strengthen throughout the twenty-first century, suggesting that the Sahel will experience particularly marked increases in extreme rain. The remarkably rapid intensification of Sahelian MCSs since the 1980s sheds new light on the response of organized tropical convection to global warming, and challenges conventional projections made by general circulation models