The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition

The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual\u27s overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This \u27epigenetic drift\u27 impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well"

Prediction of Mechanical Properties of Polymers With Various Force Fields

The effect of force field type on the predicted elastic properties of a polyimide is examined using a multiscale modeling technique. Molecular Dynamics simulations are used to predict the atomic structure and elastic properties of the polymer by subjecting a representative volume element of the material to bulk and shear finite deformations. The elastic properties of the polyimide are determined using three force fields: AMBER, OPLS-AA, and MM3. The predicted values of Young s modulus and shear modulus of the polyimide are compared with experimental values. The results indicate that the mechanical properties of the polyimide predicted with the OPLS-AA force field most closely matched those from experiment. The results also indicate that while the complexity of the force field does not have a significant effect on the accuracy of predicted properties, small differences in the force constants and the functional form of individual terms in the force fields determine the accuracy of the force field in predicting the elastic properties of the polyimide

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations

Functional polymorphisms associated with human muscle size and strength

Introduction: Skeletal muscle is critically important to human performance and health, but little is known of the genetic factors influencing muscle size, strength, and its response to exercise training. The Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength, or FAMuSS, Study is a multicenter, NIH-funded program to examine the influence of gene polymorphisms on skeletal muscle size and strength before and after resistance exercise training. Methods: One thousand men and women, age 18-40 yr, will train their nondominant arm for 12 wk. Skeletal muscle size (magnetic resonance imaging) and isometric and dynamic strength will be measured before and after training. Individuals whose baseline values or response to training deviate ≥ 1.5 SD will be defined as outliers and examined for genetic variants. Initially candidate genes previously associated with muscle performance will be examined, but the study will ultimately attempt to identify genes associated with muscle performance. Conclusion: FAMuSS should help identify genetic factors associated with muscle performance and the response to exercise training. Such insight should contribute to our ability to predict the individual response to exercise training but may also contribute to understanding better muscle physiology, to identifying individuals who are susceptible to muscle loss with environmental challenge, and to developing pharmacologic agents capable of preserving muscle size and function

Leptin Responses To Long-Term Cardiorespiratory Exercise Training Without Concomitant Weight Loss: A Prospective Study

Aim. The aims of the present study were to examine 1) whether changes in circulating leptin levels occur in response to six months of aerobic exercise training (ET) without concomitant weight loss; 2) whether there is a different response with respect to gender; and 3) the relationship between age and leptin and whether this relationship has any impact on the response to ET without weight-loss. Methods. Thirty-eight healthy, sedentary men and women (age 38.43±2.24, range 18-59 years) participated in 6 months of supervised, moderate intensity (ET) performed 4 days per week. Maintenance of usual dietary practices were encouraged to minimize weight-loss. Participants were evaluated for circulating fasting leptin, body mass, body fat percentage and maximal aerobic power (V̇O2max) prior to and after ET. Results. There was no decrease in body weight or leptin concentration (17.69±2.67 vs 16.85±3.12 ng dL-1). Gender did not affect the response to exercise training. The bivariate correlation between leptin and age was not significant, but the relationship reached significance after controlling for body fat percentage and V̇O2max (r=-0.358, P\u3c0.05). Age did not affect the response of leptin concentration to ET. Conclusion. It is probable that changes in leptin concentration reported previously with ET may be attributable to concomitant weight loss, but age does not play a role in how leptin responds to ET

Use of palmae wax hydrocarbon fractions as chemotaxonomical markers in Butia and Syagrus

The wax hydrocarbon fractions of native Butia and Syagrus species collected from Palms in different regions of the of Rio Grande do Sul state (Brazil) and in Rocha (Uruguay) were analyzed to evaluate their potential as chemotaxonomic markers. The wax was extracted with chloroform and the resulting wax was fractionated by preparative TLC. The hydrocarbon fractions were analyzed by GC-MS. Statistical analyses were completed with the Statistica 5.0 program. The total crude wax yields averaged 0.31% w.w-1 dried leaves for Butia samples and 0.28% for Syagrus samples. The linear hydrocarbons represented on average 15% of the total waxes in the case of Butia samples and 13.7% in Syagrus samples. Hentriacontane and triacontane were the main components of all samples. The comparison of the means showed significant differences among Butia and Syagrus samples, and amongst Butia samples collected in different localities. In the case of the Syagrus collections no consistent groupings could be made. In the case of Butia samples the formation of three groupings could be observed, which were consistent with the species described for their geographical distribution. These results are discussed in the paper