Living long and ageing well: is epigenomics the missing link between nature and nurture?

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50 % of the variability in human lifespan with another 25 % explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.

Exodus? The training paths and plans of postgraduate medical trainees, under the Royal College of Physicians of Ireland

Background: In 2006, the Buttimer report highlighted the paucity of demographic data on those applying for and entering postgraduate medical education and training (PGMET) in Ireland. Today, concerns that there is an "exodus" of graduates of Irish medical schools are at the forefront of national discussion, however, published data on PGMET remains inadequate.

Aims: The objectives of this study were to collate existing data relating to trainees and training programmes at three stages of training and to examine the career plans of junior trainees.

Methods: Data from application forms for training programmes, commencing July 2012, under the Royal College of Physicians of Ireland (n = 870), were integrated with data from other existing sources. Candidates entering basic specialist training were surveyed with regard to career plans. Descriptive and comparative analysis was performed in SPSS version 18.

Results: Graduates of Irish medical schools made up over 70 % of appointees. Over 80 % of BST trainees aspired to work as consultants in Ireland, but 92.5 % planned to spend time working abroad (response rate 77 %). Decisions to leave the Irish system were linked to lifestyle, but also to failure to be appointed to higher specialist training. Significant numbers of trainees return to Ireland after a period abroad.

Conclusions: The trainee "exodus" is more complex than is often portrayed. The desire to spend time working outside Ireland must be accounted for in workforce planning and configuration of training programmes. Expansion of HST is a potential solution to reduce the numbers of graduates leaving Ireland post-BST.

Unsettling modernity: Shifting values and changing housing styles in the Kathmandu Valley

Abstract

Culture has always been important for the character of the cities, as have the civic and public institutions that sustain a lifestyle and provide an identity. Substantial evidence of the unique historical, urban civilisation remains within the traditional settlements in the Kathmandu Valley in Nepal; manifested in houses, palaces, temples, rest houses, open spaces, festivals, rituals, customs and cultural institutions. Indigenous knowledge and practices prescribed the arrangement of houses, roads and urban spaces giving the city a distinctive physical form, character and a unique oriental nativeness. In technical sense, these societies did not have written rules for guiding development. In recent decades, the urban culture of the city has been changing with the forces of urbanisation and globalisation and the demand for new buildings and spaces. New residential design is increasingly dominated by distinctive patterns of Western suburban ideal comprising detached or semi-detached homes and high rise tower blocks. This architectural iconoclasm can be construed as a rather crude response to the indigenous culture and built form. The paper attempts to dismantle the current tension between traditional and contemporary ‘culture’ (and hence society) and housing (or built form) in the Kathmandu Valley by engaging in a discussion that cuts across space, time and meaning of architecture as we know it.

Ophthalmic epidemiology in Europe: the “European Eye Epidemiology” (E3) consortium

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

Risk factors (excluding hormone therapy) for endometrial hyperplasia: a systematic review.

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH).

Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015.

Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories.

Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk.

Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Willingness to pay for personalised nutrition across Europe

BACKGROUND: Personalised nutrition (PN) may promote public health. PN involves dietary advice based on individual characteristics of end users and can for example be based on lifestyle, blood and/or DNA profiling. Currently, PN is not refunded by most health insurance or health care plans. Improved public health is contingent on individual consumers being willing to pay for the service.

METHODS: A survey with a representative sample from the general population was conducted in eight European countries (N= 8233). Participants reported their willingness to pay (WTP) for PN based on lifestyle information, lifestyle and blood information, and lifestyle and DNA information. WTP was elicited by contingent valuation with the price of a standard, non-PN advice used as reference.

RESULTS: About 30% of participants reported being willing to pay more for PN than for non-PN advice. They were on average prepared to pay about 150% of the reference price of a standard, non-personalised advice, with some differences related to socio-demographic factors.

CONCLUSION: There is a potential market for PN compared to non-PN advice, particularly among men on higher incomes. These findings raise questions to what extent personalized nutrition can be left to the market or should be incorporated into public health programs.