Accelerated epigenetic aging in Werner syndrome.

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown

Motor skills in children with primary headache: A pilot case-control study

Background: Headache is the most common painful manifestation in the developmental age, often accompanied by severe disability such as scholastic absenteeism, low quality of academic performance and compromised emotional functioning. The aim of the study is to evaluate praxic abilities in a population of children without aural migraine. Materials and methods: The test population consists of 10 subjects without migraine without aura (MwA), (8 Males) (mean age 8.40, SD ± 1.17) and 11 healthy children (7 Males) (mean age 8.27; SD ± 1.10; p = 0.800). All subjects underwent evaluation of motor coordination skills through the Battery for Children Movement Assessment (M-ABC). Results: The two groups (10 MwA vs 11 Controls) were similar for age (8.40 ± 1.17 vs 8.27 ± 1.10; p = 0.800), sex (p = 0.730), and BMI (p = 0.204). The migraine subjects show an average worse performance than the Movement ABC; specifically, migraineurs show significantly higher total score values (31.00 ± 23.65 vs 4.72 ± 2.61; p = 0.001), manual dexterity (12.10 ± 11.20 vs 2.04 ± 2.65; p = 0.009) and balance (14.85 ± 10.08 vs. 1.04 ± 1.05; p <0.001). The mean percentile of migraine performance is significantly reduced compared to controls (9.00 ± 3.82 vs 51.00 ± 24.34, p <0.001) (Table 1). Conclusion: Migraine can alter many cognitive and executive functions such as motor skills in developmental age

The influence of socioeconomic deprivation on multimorbidity at different ages: a cross-sectional study

<b>Background</b> Multimorbidity occurs at a younger age in individuals in areas of high socioeconomic deprivation but little is known about the 'typology' of multimorbidity in different age groups and its association with socioeconomic status.<p></p> <b>Aim</b> To characterise multimorbidity type and most common conditions in a large nationally representative primary care dataset in terms of age and deprivation.<p></p> <b>Design and setting</b> Cross-sectional analysis of 1 272 685 adults in Scotland.<p></p> <b>Method</b> Multimorbidity type of participants (physical-only, mental-only, mixed physical, and mental) and most common conditions were analysed according to age and deprivation.<p></p> <b>Results</b> Multimorbidity increased with age, ranging from 8.1% in those aged 25–34 to 76.1% for those aged ≥75 years. Physical-only (56% of all multimorbidity) was the most common type of multimorbidity in those aged ≥55 years, and did not vary substantially with deprivation. Mental-only was uncommon (4% of all multimorbidity), whereas mixed physical and mental (40% of all multimorbidity) was the most common type of multimorbidity in those aged <55 years and was two- to threefold more common in the most deprived compared with the least deprived in most age groups. Ten conditions (seven physical and three mental) accounted for the top five most common conditions in people with multimorbidity in all age groups. Depression and pain featured in the top five conditions across all age groups. Deprivation was associated with a higher prevalence of depression, drugs misuse, anxiety, dyspepsia, pain, coronary heart disease, and diabetes in multimorbid patients at different ages.<p></p> <b>Conclusion</b> Mixed physical and mental multimorbidity is common across the life-span and is exacerbated by deprivation from early adulthood onwards

Peroxisome Proliferator-activated receptor alpha gene variation influences age of onset and progression of type 2 diabetes

Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR) is a master regulator of fatty acid catabolism, and PPAR activators delay the onset of type 2 diabetes. We examined association between three PPAR gene polymorphisms (an AC variant in intron 1, the L162V variant, and the intron 7 GC variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPAR gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 AC (P < 0.001) and intron 7 GC (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPAR haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis 45 years) of 3.75 (95% CI 1.65–8.56, P = 0.002). Intron 1 C-allele carriers also progressed more rapidly to insulin monotherapy (AA 9.4 ± 1.5 and AC + CC 5.3 ± 1.1 years, P = 0.002). These data indicate that PPAR gene variation influences the onset and progression of type 2 diabetes

In utero DDT and DDE exposure and obesity status of 7-year-old Mexican-American children in the CHAMACOS cohort.

BackgroundIn utero exposure to endocrine disrupting compounds including dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) has been hypothesized to increase risk of obesity later in life.ObjectivesThe Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a longitudinal birth cohort of low-income Latinas living in a California agricultural community. We examined the relation of in utero DDT and DDE exposure to child obesity at 7 years of age. We also examined the trend with age (2, 3.5, 5, and 7 years) in the exposure-obesity relation.MethodsWe included 270 children with o,p´-DDT, p,p´-DDT, and p,p´-DDE concentrations measured in maternal serum during pregnancy (nanograms per gram lipid) and complete 7-year follow-up data including weight (kilograms) and height (centimeters). Body mass index (BMI; kilograms per meter squared) was calculated and obesity was defined as ≥ 95th percentile on the sex-specific BMI-for-age Centers for Disease Control and Prevention 2000 growth charts.ResultsAt 7 years, 96 (35.6%) children were obese. A 10-fold increase in o,p´-DDT, p,p´-DDT, or p,p´-DDE, was nonsignificantly associated with increased odds (OR) of obesity [o,p´-DDT adjusted (adj-) OR = 1.17, 95% CI: 0.75, 1.82; p,p´-DDT adj-OR = 1.19, 95% CI: 0.81, 1.74; p,p´-DDE adj-OR = 1.22, 95% CI: 0.72, 2.06]. With increasing age at follow-up, we observed a significant trend toward a positive association between DDT and DDE exposure and odds of obesity.ConclusionWe did not find a significant positive relation between in utero DDT and DDE exposure and obesity status of 7-year-old children. However, given the observed trend with age, continued follow-up will be informative

Biases in the relationship between dream threats and level of anxiety upon awakening

Objectives:\ud Controlling report length in dream content analysis comprises a significant methodological problem. Individual differences occur in report length which can influence category coding and rating scales. Differences are also found in dream content by sex and age. The aim of this study is to determine the bias of certain variables in dream content analysis when using rating scales, coding systems and questionnaires. As such, an evaluation was performed of the bias of these variables on the relationship between anxiety upon awakening, social threats (ST) and terrifying threats (TT) established in a previous study.\ud Methods: The sample consisted of 215 dreams collected in dreamers' homes (63 belonged to men and 152 to women). The dreamer's level of anxiety upon awakening was assessed with the CEAD. The level of social and terrifying threats in the content of the dreams was also assessed. Other variables entered into the analysis were sex, age, dream length, number of hours before answering the questionnaire, number of hours' sleep and the frequency with which the dreamer suffers nightmares.\ud Results:\ud Use of the Mann Whitney U found significant differences by sex in the dreamer's nightmare frequency (z=-2.53 p=.011), in terrifying threats in the dream (z=-2.03 p= .042) and by dream time (z=-2.51 p=.012). The Spearman Rho correlation coefficient indicated a positive relationship between anxiety upon awakening and nightmare frequency (Rho=.26 p<.001). Social and terrifying threats were also positively correlated with word count and the number of dream characters (Rho=.37 p<.001, Rho=.17 p=.010). Both anxiety upon awakening and social and terrifying threats were negatively correlated with the age of the dreamer (RhoCEAD-AGE=-.20 p=.006, RhoST-AGE=-.30 p<.001, RhoTT-AGE=-.37 p<.001). Possible biases due to sex, age, word count and the number of characters were statistically controlled by means of partial correlation. Through the use of partial correlations, the significance between anxiety upon awakening, social threats and terrifying threats in the dream was observed to be maintained (rCEAD-TS=.17 p=.025, rCEAD-TT=.19 p=.011).\ud Conclusion:\ud The sex, age of the dreamer, the report word count and the number of dream characters must be controlled in research into dream content. In addition, after eliminating these biases, a significant relationship was confirmed between threats which appear in the dream and the dreamer's level of anxiety upon awakening

Aging in Structural Changes of Amorphous Solids: A Study of First Passage Time and Persistence Time Distribution

The time distribution of relaxation events in an aging system is investigated via molecular dynamics simulations. The focus is on the distribution functions of the first passage time, $p_1(\Delta t)$, and the persistence time, $p(\tau)$. In contrast to previous reports, both $p_1$ and $p$ are found to evolve with time upon aging. The age dependence of the persistence time distribution is shown to be sensitive to the details of the algorithm used to extract it from particle trajectories. By updating the reference point in event detection algorithm and accounting for the event specific aging time, we uncover age dependence of $p(\tau)$, hidden to previous studies. Moreover, the apparent age-dependence of $p_1$ in continuous time random walk with an age independent $p(\tau)$ is shown to result from an implicit synchronization of all the random walkers at the starting time