Diabetes mellitus type 2 (T2D) is associated with accelerated biological aging and the increased risk of onset of other age-related diseases. Epigenetic changes in DNA methylation levels have been found to serve as reliable biomarkers for biological aging. This study explores the relationship between various epigenetic biomarkers of aging and diabetes risk using longitudinal data.
View Article and Find Full Text PDFThe suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of VipNms SCN neurons at night.
View Article and Find Full Text PDFAging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging.
View Article and Find Full Text PDFPrimary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at high risk of severe COVID-19 and protection against SARS-CoV-2 is therefore important. We studied facemask usage and problems reported in relation with their use among people with PCD.
View Article and Find Full Text PDFBackground: Biomarker-disease relationships are extensively investigated. However, associations between common clinical biomarkers and healthspan, the disease-free lifespan, are largely unknown. We aimed to explore the predictive values of ten biomarkers on healthspan and lifespan, and to identify putative causal mechanisms.
View Article and Find Full Text PDFIntroduction: Tonsillectomy is one of the most common procedures in the field of ear, nose and throat procedures. In 2012, the annual incidence in Denmark was 129.4 per 100,000 inhabitants.
View Article and Find Full Text PDFBackground: The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.
View Article and Find Full Text PDFIntroduction: Eicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available.
View Article and Find Full Text PDFIntroduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.
View Article and Find Full Text PDFThe unique properties of graphene, transition-metal dichalcogenides and other two-dimensional (2D) materials have boosted interest in layered coordination solids. In particular, 2D materials that behave as both conductors and magnets could find applications in quantum magnetoelectronics and spintronics. Here, we report the synthesis of CrCl(pyrazine), an air-stable layered solid, by reaction of CrCl with pyrazine (pyz).
View Article and Find Full Text PDFSeveral studies have linked DNA methylation at individual CpG sites to aging and various diseases. Recent studies have also identified single CpGs whose methylation levels are associated with all-cause mortality. In this study, we perform an epigenome-wide study of the association between CpG methylation and mortality in a population of 435 monozygotic twin pairs from three Danish twin studies.
View Article and Find Full Text PDFRationale: Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention.
View Article and Find Full Text PDFPurpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction.
View Article and Find Full Text PDFThe search for reliable indicators of biological age, rather than chronological age, has been ongoing for over three decades, and until recently, largely without success. Advances in the fields of molecular biology have increased the variety of potential candidate biomarkers that may be considered as biological age predictors. In this review, we summarize current state-of-the-art findings considering six potential types of biological age predictors: epigenetic clocks, telomere length, transcriptomic predictors, proteomic predictors, metabolomics-based predictors, and composite biomarker predictors.
View Article and Find Full Text PDFThe prevalence of obesity and related conditions like non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and therapeutic options are limited. Alternative treatment options are therefore intensively sought after. An interesting candidate is the natural polyphenol resveratrol (RSV) that activates adenosinmonophosphate-activated protein kinase (AMPK) and silent information regulation-2 homolog 1 (SIRT1).
View Article and Find Full Text PDFThe classical view that endocytosis serves only for growth factor receptor degradation and signaling termination has recently been challenged by an increasing number of reports showing that various growth factor receptors such as epidermal growth factor receptor (EGFR) continue to activate downstream signaling molecules en route to lysosomes prior to their degradation. Moreover, the trafficking route that the ligand-receptor complexes follow to enter the cell is mutually interconnected with the final signaling output. Endosomal resident effector proteins are compartmentalized and regulate the signaling and trafficking of the ligand-bound receptor complexes.
View Article and Find Full Text PDFSmad anchor for receptor activation (SARA) is highly enriched on endocytic membranes via binding to phosphatidylinositol 3-phosphates through its FYVE (Fab1p-YOTB-Vps27p-EEA1) domain. SARA was originally identified as a protein that recruits non-phosphorylated SMAD2/3 to the activated TGFβ receptors for phosphorylation, but later reports suggested a regulatory role in endocytic trafficking. Here we demonstrate that the ubiquitin ligase RNF11 is a SARA-interacting protein residing on early and late endosomes, as well as the fast recycling compartment.
View Article and Find Full Text PDFSix cores were drilled and retrieved from 186-m depth in the Äspö Hard Rock Laboratory (HRL) tunnel to investigate whether indigenous biofilms develop on fracture surfaces in groundwater-conducting aquifers in granitic rock. A clone library was constructed from fracture surface material (FSM), for community composition analysis. Quantitative polymerase chain reaction (qPCR) was applied to quantify gene copies using the 16S rRNA gene for domain Bacteria and the adenosine-phosphosulfate reductase gene (apsA) for sulfate-reducing bacteria (SRB).
View Article and Find Full Text PDFFicolins are soluble molecules that bind carbohydrate present on the surface of microorganisms and function as recognition molecules in the lectin complement pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and ficolin-3. Ficolin-1 is synthesized in monocytes and type II alveolar epithelial cells.
View Article and Find Full Text PDFThis study used a sample of 551 children surveyed yearly from ages 6 to 13 to examine the longitudinal associations among early behavior, middle-childhood peer rejection and friendedness, and early-adolescent depressive symptoms, loneliness, and delinquency. The study tested a sequential mediation hypothesis in which (a) behavior problems in the early school years are associated with middle-childhood peer rejection and (b) rejection, in turn, leads to lower friendedness and subsequently higher adolescent internalizing--but not externalizing--problems. Results supported this sequential mediation model for internalizing outcomes and revealed an additional path from early disruptiveness to loneliness via peer rejection alone.
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