Attitudes to ageing, biomarkers of ageing and mortality:The Lothian Birth Cohort 1936

Objective: To investigate whether people with more positive attitudes to ageing are biologically younger as defined by leucocyte telomere length, accelerated DNA methylation GrimAge (AgeAccelGrim) and brain-predicted age difference, and whether these biomarkers explain relationships between attitudes to ageing and mortality.Methods: We used linear regression to examine cross-sectionally attitudes to ageing (measured using the Attitudes to Ageing Questionnaire) and the three biomarkers in 758 adults, mean age 72.5 years, from the Lothian Birth Cohort 1936. We used Cox proportional hazards models to examine longitudinally attitudes to ageing and mortality and the role of the biomarkers.Results: More positive attitude to physical change was associated with younger biological age, as measured by AgeAccelGrim and brain-predicted age difference in age-adjusted and sex-adjusted models: for an SD higher score, AgeAccelGrim was lower by -0.73 (95% CI -1.03 to -0.42) of a year, and brain-predicted age difference was lower by -0.87 (1.51 to 0.23) of a year. Both associations were attenuated by adjustment for covariates and not significant after simultaneous adjustment for all covariates and correction for multiple testing. More positive attitudes to physical change were associated with lower mortality: for an SD higher score the age-adjusted and sex-adjusted HR (95% CI) was 0.66 (0.56 to 0.78). Adjustment for AgeAccelGrim or brain-predicted age difference attenuated this association slightly. It remained significant after adjustment for all covariates.Conclusion: We found partial evidence that attitudes to ageing are linked with ageing biomarkers but they accounted for only a little of the association between attitudes and mortality

Modelling and mapping how common guillemots balance their energy budgets over a full annual cycle

The ability of individual animals to balance their energy budgets throughout the annual cycle is important for their survival, reproduction and population dynamics. However, the annual cycles of many wild, mobile animals are difficult to observe and our understanding of how individuals balance their energy budgets throughout the year therefore remains poor. We developed a hierarchical Bayesian state-space model to investigate how key components of animal energy budgets (namely individual energy gain and storage) varied in space and time. Our model used biologger-derived estimates of time-activity budgets, locations and energy expenditure to infer year-round time series of energy income and reserves. The model accounted for seasonality in environmental drivers such as sea surface temperature and daylength, allowing us to identify times and locations of high energy gain. Our study system was a population of common guillemots Uria aalge breeding at a western North Sea colony. These seabirds manage their energy budgets by adjusting their behaviour and accumulating fat reserves. However, typically during severe weather conditions, birds can experience an energy deficit over a sustained period, leading to starvation and large-scale mortality events. We show that guillemot energy gain varied in both time and space. Estimates of guillemot body mass varied throughout the annual cycle and birds periodically experienced losses in mass. Mass losses were likely to have either been adaptive, or due to energetic bottlenecks, the latter leading to increased susceptibility to mortality. Guillemots tended to be lighter towards the edge of their spatial distribution. We describe a framework that combines biologging data, time-activity budget analysis and Bayesian state-space modelling to identify times and locations of high energetic reward or potential energetic bottlenecks in a wild animal population. Our approach can be extended to address ecological and conservation-driven questions that were previously unanswerable due to logistical complexities in collecting data on wild, mobile animals across full annual cycles

Sleep disturbance and the older worker:Findings from the Health and Employment After Fifty study

Objectives: The aim of this study was to characterize the descriptive epidemiology of insomnia in midlife and explore the relative importance of different occupational risk factors for insomnia among older workers.Methods: A questionnaire was mailed to all adults aged 50–64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past three months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated.Results: Analysis was based on 8067 respondents (5470 in paid work), 18.8% of whom reported insomnia. It was more common among women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent among the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticized). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work [population attributable fraction (PAF) 15–33%] than shift work and lack of autonomy or support (PAF 5–7%). It was strongly associated with seven measures of poorer self-assessed health.Conclusions: Employment policies aimed at tackling insomnia among older workers may benefit from focusing particularly on job–person fit, job security and relationships in the workplace.<br/

Sex-specific moderation by lifestyle and psychosocial factors on the genetic contributions to adiposity in 112,151 individuals from UK Biobank

Abstract Evidence suggests that lifestyle factors, e.g. physical activity, moderate the manifestation of genetic susceptibility to obesity. The present study uses UK Biobank data to investigate interaction between polygenic scores (PGS) for two obesity indicators, and lifestyle and psychosocial factors in the prediction of the two indicators, with attention to sex-specific effects. Analyses were of 112 151 participants (58 914 females; 40 to 73 years) whose genetic data passed quality control. Moderation effects were analysed in linear regression models predicting body mass index (BMI) and waist-to-hip ratio (WHR), including interaction terms for PGS and each exposure. Greater physical activity, more education, higher income, moderate vs low alcohol consumption, and low material deprivation were each associated with a relatively lower risk for manifestation of genetic susceptibility to obesity (p < 0.001); the moderating effects of physical activity and alcohol consumption were greater in women than men (three-way interaction: p = 0.009 and p = 0.008, respectively). More income and less neuroticism were related to reduced manifestation of genetic susceptibility to high WHR (p = 0.007; p = 0.003); the effect of income was greater in women (three-way interaction: p = 0.001). Lifestyle and psychosocial factors appear to offset genetic risk for adiposity in mid to late adulthood, with some sex-specific associations

Reaction time and onset of psychological distress:The UK Health and Lifestyle Survey

BACKGROUND: Cross-sectional studies have shown that depression is often accompanied by less efficient cognitive function, as indicated by slower speed of information processing. The direction of effect is unclear. We investigated prospectively whether slower processing speed, as indexed by longer simple or choice reaction time, is associated with an increased risk of psychological distress. METHODS: Participants were 3088 men and women aged 18 and over who had taken part in the UK Health and Lifestyle Survey. Simple and choice reaction time was measured in the baseline survey. Symptoms of psychological distress were assessed at baseline and at the 7-year follow-up survey with the 30-item General Health Questionnaire (GHQ). RESULTS: In unadjusted models, a SD slower simple or choice reaction time at baseline was associated with ORs for psychological distress (≥5 on GHQ) at follow-up of 1.14 (1.06 to 1.23; p<0.001) or 1.13 (1.04 to 1.22; p=0.002), respectively. Further adjustment for age, sex, social class, educational attainment, health behaviours, number of chronic physical illnesses present, neuroticism and GHQ score at baseline had only slight attenuating effects on these associations. In fully adjusted models, a SD slower simple or choice reaction time at baseline was associated with ORs for psychological distress of 1.11 (1.02 to 1.21; p=0.017) or 1.11 (1.00 to 1.24; p=0.048), respectively. CONCLUSIONS: Slower processing speed may be a risk factor for the development of psychological distress. Future studies should explore the extent to which slower processing speed explains previously demonstrated associations between lower intelligence and poorer mental health

Genetic contributions to trail making test performance in UK Biobank

The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B−part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg&gt;0.6), general cognitive function (rg&gt;0.6), processing speed (rg&gt;0.7) and memory (rg&gt;0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized β between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.</p

GWAS on family history of Alzheimer’s disease

Alzheimer’s disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer’s dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P &lt; 5 × 10−8) are identified. These contain genes relevant for AD and neurodegeneration: ADAM10, BCKDK/KAT8 and ACE. Novel gene-based loci include drug targets such as VKORC1 (warfarin dose). We report evidence that the association of SNPs in the TOMM40 gene with AD is potentially mediated by both gene expression and DNA methylation in the prefrontal cortex. However, it is likely that multiple variants are affecting the trait and gene methylation/expression. Our discovered loci may help to elucidate the biological mechanisms underlying AD and, as they contain genes that are drug targets for other diseases and disorders, warrant further exploration for potential precision medicine applications

Frailty, prefrailty and employment outcomes in Health and Employment After Fifty (HEAF) Study

Objectives Demographic changes are requiring people to work longer. No previous studies, however, have focused on whether the ‘frailty’ phenotype (which predicts adverse events in the elderly) is associated with employment difficulties. To provide information, we assessed associations in the Health and Employment After Fifty Study, a population-based cohort of 50–65-year olds.Methods Subjects, who were recruited from 24 English general practices, completed a baseline questionnaire on ‘prefrailty’ and ‘frailty’ (adapted Fried criteria) and several work outcomes, including health-related job loss (HRJL), prolonged sickness absence (&gt;20 days vs less, past 12 months), having to cut down substantially at work and difficulty coping with work's demands. Associations were assessed using logistic regression and population attributable fractions (PAFs) were calculated.Results In all, 3.9% of 8095 respondents were classed as ‘frail’ and 31.6% as ‘prefrail’. Three-quarters of the former were not in work, while 60% had left their last job on health grounds (OR for HRJL vs non-frail subjects, 30.0 (95% CI 23.0 to 39.2)). Among those in work, ORs for prolonged sickness absence, cutting down substantially at work and struggling with work's physical demands ranged from 10.7 to 17.2. The PAF for HRJL when any frailty marker was present was 51.8% and that for prolonged sickness absence was 32.5%. Associations were strongest with slow reported walking speed. Several associations were stronger in manual workers than in managers.Conclusions Fried frailty symptoms are not uncommon in mid-life and are strongly linked with economically important adverse employment outcomes. Frailty could represent an important target for prevention.</p

Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936

Background: Exposure to air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) offer potential mechanistic insights into human health differences, connecting disease pathogenesis and biological ageing. However, little is known about sensitive periods during the life course where air pollution might have a stronger impact on DNAm, or whether effects accumulate over time. We examined associations between air pollution exposure across the life course and DNAm-based markers of biological ageing. Methods: Data were derived from the Scotland-based Lothian Birth Cohort 1936. Participants’ residential history was linked to annual levels of fine particle (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) around 1935, 1950, 1970, 1980, 1990, and 2001; pollutant concentrations were estimated using the EMEP4UK atmospheric chemistry transport model. Blood samples were obtained between ages of 70 and 80 years, and Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, DNAmGrimAge, and DNAm telomere length (DNAmTL) were computed. We applied the structured life-course modelling approach: least angle regression identified best-fit life-course models for a composite measure of air pollution (air quality index [AQI]), and mixed-effects regression estimated selected models for AQI and single pollutants. Results: We included 525 individuals with 1782 observations. In the total sample, increased air pollution around 1970 was associated with higher epigenetic age (AQI: b=0.322 year, 95%CI: 0.088, 0.555) measured with Horvath DNAmAge in late adulthood. We found shorter DNAmTL among males with higher air pollution around 1980 (AQI: b=-0.015 kilobase, 95%CI: -0.027, -0.004) and among females with higher exposure around 1935 (AQI: b=-0.017 kilobase, 95%CI: -0.028, -0.006). Findings were more consistent for the pollutants PM2.5, SO2 and NO2. Discussion: We tested the life-course relationship between air pollution and DNAm-based biomarkers. Air pollution around birth and in young-to-middle adulthood is linked to accelerated epigenetic ageing and telomere-associated ageing in later life

Job dissatisfaction and the older worker:Baseline findings from the Health and Employment After Fifty study

Objectives: Demographic changes are requiring people to work longer. Labour force participation might be promoted by tackling sources of job dissatisfaction. We aimed to describe the epidemiology of job dissatisfaction in older British workers, to explore which perceptions of work contribute most importantly, and to assess possible impacts on health.Methods: Participants aged 50–64?years were recruited from 24 English general practices. At baseline, those currently in work (N=5437) reported on their demographic and employment circumstances, overall job satisfaction, perceptions of their work that might contribute to dissatisfaction, and their general health, mood and well-being. Associations of job dissatisfaction with risk factors and potential health outcomes were assessed cross-sectionally by logistic regression, and the potential contributions of different negative perceptions to overall dissatisfaction were summarised by population attributable fractions (PAFs).Results: Job dissatisfaction was more common among men, below age 60?years, those living in London and the South East, in the more educated and in those working for larger employers. The main contributors to job dissatisfaction among employees were feeling unappreciated and/or lacking a sense of achievement (PAF 55–56%), while in the self-employed, job insecurity was the leading contributor (PAF 79%). Job dissatisfaction was associated with all of the adverse health outcomes examined (ORs of 3–5), as were most of the negative perceptions of work that contributed to overall dissatisfaction.Conclusions: Employment policies aimed at improving job satisfaction in older workers may benefit from focussing particularly on relationships in the workplace, fairness, job security and instilling a sense of achievement.<br/