The Jackson Laboratory Nathan Shock Center: impact of genetic diversity on aging.

Healthspan is a complex trait, influenced by many genes and environmental factors that accelerate or delay aging, reduce or increase disease risk, and extend or reduce lifespan. Thus, assessing the role of genetic variation in aging requires an experimental strategy capable of modeling the genetic and biological complexity of human populations. The goal of the The Jackson Laboratory Nathan Shock Center (JAX NSC) is to provide research resources and training for geroscience investigators that seek to understand the role of genetics and genetic diversity on the fundamental process of aging and diseases of human aging using the laboratory mouse as a model system. The JAX NSC has available novel, deeply characterized populations of aged mice, performs state-of-the-art phenotyping of age-relevant traits, provides systems genetics analysis of complex data sets, and provides all of these resources to the geroscience community. The aged animal resources, phenotyping capacity, and genetic expertise available through the JAX NSC benefit the geroscience community by fostering cutting-edge, novel lines of research that otherwise would not be possible. Over the past 15 years, the JAX NSC has transformed aging research across the geroscience community, providing aging mouse resources and tissues to researchers. All JAX NSC data and tools are publicly disseminated on the Mouse Phenome Database and the JAX NSC website, thus ensuring that the resources generated and expertise acquired through the Center are readily available to the aging research community. The JAX NSC will continue to enhance its ability to perform innovative research using a mammalian model to illuminate novel genotype-phenotype relationships and provide a rational basis for designing effective risk assessments and therapeutic interventions to boost longevity and disease-free healthspan

The association of acylcarnitines and amino acids with age in Dutch and South-Asian Surinamese living in Amsterdam.

Type 2 diabetes and cardiovascular disease occur more frequently, and at a younger age in South-Asians than Europeans. This may be related to differences in regulation of the fatty acid metabolism during aging. We compared age-related acylcarnitine and amino acid concentrations. We measured types of acylcarnitine and amino acid concentrations in plasma (by tandem-MS) in a random subsample of 350 Dutch and 350 South-Asian Surinamese origin participants of the HELIUS study (Amsterdam, The Netherlands). We derived principal components (PCs) from the metabolites. Linear regression was used to assess differences in PCs and individual metabolite concentrations, and their age-trends between the groups by sex. We adjusted for BMI and intake of fat and total energy. Mean age was 44.8 (SD 13.3) years. Many metabolite concentrations were higher among South-Asian Surinamese participants compared to Dutch participants; amino acids in women, and both acylcarnitines and amino acids in men. Metabolite levels increased similarly with age in both ethnic groups. Results remained similar after adjustment. Ethnic differences in metabolite concentrations suggest that fatty acid and amino acid metabolism are more dysregulated among South-Asian Surinamese compared to Dutch from a young age. During adulthood metabolites increase similarly in both ethnic groups

Effects on cardiovascular disease risk of a web-based health risk assessment with tailored health advice: A follow-up study

Introduction: A large proportion of the cardiovascular disease (CVD) burden can potentially be prevented by primary prevention programs addressing major causal risk factors. A Web- based health risk assessment (HRA) with tailored feedback for individual health promotion is a promising strategy. We evaluated the effect on CVD risk of such a program among employees of a Dutch worksite. Methods: We conducted a prospective follow-up study among 368 employees who voluntarily participated in a Web-based HRA program at a single Dutch worksite in 2008. The program included a multicomponent HRA through a Web-based electronic questionnaire, biometrics, and laboratory evaluation. The results were combined with health behavior change theory to generate tailored motivational and educational health advice. On request, a health counseling session with the program physician was available. Follow-up data on CVD risk were collected 1 year after initial participation. The primary outcome was a change in Framingham CVD risk at 6 months relative to baseline. We checked for a possible background effect of an increased health consciousness as a consequence of program introduction at the worksite by comparing baseline measurements of early program participants with baseline measurements of participants who completed the program 6 months later. Results: A total of 176 employees completed follow-up measurements after a mean of 7 months. There was a graded relation between CVD risk changes and baseline risk, with a relative reduction of 17.9% (P = 0.001) in the high-risk category (baseline CVD risk ≥20%). Changes were not explained by additional health counseling, medication, or an increase in health consciousness within the company. Conclusions: Voluntary participation in a Web-based HRA with tailored feedback at the worksite reduced CVD risk by nearly 18% among participants at high CVD risk and by nearly 5% among all participants. Web-based HRA could improve CVD risk in similar populations. Future research should focus on the persistence of the effects underlying the CVD risk reduction

Ethnic differences in current smoking and former smoking in the Netherlands and the contribution of socioeconomic factors: a cross-sectional analysis of the HELIUS study.

OBJECTIVES: Data exploring how much of the ethnic differences in smoking prevalence and former smoking are explained by socioeconomic status (SES) are lacking. We therefore assessed ethnic differences in smoking prevalence and former smoking and the contribution of both educational level and occupational-related SES to the observed ethnic differences in smoking behaviour. METHODS: Data of 22 929 participants (aged 18-70 years) from the multiethnic cross-sectional Healthy Life in an Urban Setting study in the Netherlands were analysed. Poisson regression models with a robust variance were used to estimate prevalence ratios. RESULTS: Compared with the Dutch, after adjustment for age and marital status, smoking prevalence was higher in men of Turkish (prevalence ratio 1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women, smoking prevalence was higher in Turkish, similar in African Surinamese but lower in all other ethnic origin groups. All ethnic minority groups, except Ghanaians, had a significantly lower smoking cessation prevalence than the Dutch. Socioeconomic gradients in smoking (higher prevalence among those lower educated and with lower level employment) were observed in all groups except Ghanaian women (a higher prevalence was observed in the higher educated). Ethnic differences in smoking prevalence and former smoking are largely, but not completely, explained by socioeconomic factors. CONCLUSIONS: Our findings imply that antismoking policies designed to target smoking within the lower socioeconomic groups of ethnic minority populations may substantially reduce ethnic inequalities in smoking particularly among men and that certain groups may benefit from targeted smoking cessation interventions

Relationship between educational and occupational levels, and Chronic Kidney Disease in a multi-ethnic sample- The HELIUS study

Ethnic minority groups in high-income countries are disproportionately affected by Chronic Kidney Disease (CKD) for reasons that are unclear. We assessed the association of educational and occupational levels with CKD in a multi-ethnic population. Furthermore, we assessed to what extent ethnic inequalities in the prevalence of CKD were accounted for by educational and occupational levels.Cross-sectional analysis of baseline data from the Healthy Life in an Urban Setting (HELIUS) study of 21,433 adults (4,525 Dutch, 3,027 South-Asian Surinamese, 4,105 African Surinamese, 2,314 Ghanaians, 3,579 Turks, and 3,883 Moroccans) aged 18 to 70 years living in Amsterdam, the Netherlands. Three CKD outcomes were considered using the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) severity of CKD classification. Comparisons between educational and occupational levels were made using logistic regression analyses.After adjustment for sex and age, low-level and middle-level education were significantly associated with higher odds of high to very high-risk of CKD in Dutch (Odds Ratio (OR) 2.10, 95% C.I., 1.37-2.95; OR 1.55, 95% C.I., 1.03-2.34). Among ethnic minority groups, low-level education was significantly associated with higher odds of high to very-high-risk CKD but only in South-Asian Surinamese (OR 1.58, 95% C.I., 1.06-2.34). Similar results were found for the occupational level in relation to CKD risk.The lower educational and occupational levels of ethnic minority groups partly accounted for the observed ethnic inequalities in CKD. Reducing CKD risk in ethnic minority populations with low educational and occupational levels may help to reduce ethnic inequalities in CKD and its related complications

Ideal cardiovascular health and risk of cardiovascular events in the EPIC-Norfolk prospective population study.

BACKGROUND: The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study. DESIGN: Prospective cohort study. METHODS: An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events. RESULTS AND CONCLUSION: As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P < 0.001), for stroke of 0.16 (95% CI 0.02-1.37, P = 0.09) and for cardiovascular disease of 0.07 (95% CI 0.02-0.23, P < 0.001), compared to people in the lowest (i.e. unhealthiest) category (score 0-2). The overall cardiovascular health score was strongly and inversely associated with risk of coronary heart disease, stroke and cardiovascular disease. Our data suggest that even small improvements in modifiable risk factors may lead to substantial reductions in the risks of cardiovascular events.The EPIC-Norfolk Study is funded by Cancer Research UK grant number 14136 and the Medical Research Council grant number G1000143, SL is supported by a studentship from Unilever Corporate Research, UK.This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/204748731560201