Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Mid-life social participation and physical performance at age 60-64: evidence from the 1946 British Birth Cohort Study.

BACKGROUND: Previous studies linking social activity and disability have been limited by focussing on self-reported physical performance in older adults (>65). We examined whether social participation in mid-life is associated with objective and subjective measures of physical performance in older age. METHODS: Participants of the Medical Research Council National Survey of Health and Development reported their involvement in social activities at ages 43 and 60-64 years; frequency of such involvement was classified into thirds. Physical performance was measured at age 60-64 using: grip strength; standing balance; chair rises; timed get-up-and-go; self-reported physical function from the Short Form-36. Multivariable regression was used to examine longitudinal associations between social participation and each physical performance measure. We also investigated whether change in social participation between 43 and 60-64 was associated with each outcome. RESULTS: In fully adjusted models, higher frequency of social participation at 43 was associated with faster chair rise (1.42 repetitions/min, 95% CI 0.45-2.39) and timed get-up-and-go speed (2.47 cm/s, 95% CI 0.27-4.67) and lower likelihood of self-report limitations (OR of low physical function 0.67, 95% CI 0.50-0.91) at 60-64 compared with low frequency. Better performance in objectively measured outcomes was observed only if higher social participation persisted over time whereas lower odds of self-reported limitations were found in all groups when compared to those with persistently low participation (ORs 0.43-0.56, all P≤0.02). CONCLUSION: Our findings suggest that associations between higher levels of social participation in mid-life and better physical performance exist only if this social participation persists through to older age.

Childhood adversity and DNA methylation in two population-based cohorts.

Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Sidák correction p-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.

A holistic approach to healthy ageing: how can people live longer, healthier lives?

BACKGROUND: Although lifespan is increasing, there is no evidence to suggest that older people are experiencing better health in their later years than previous generations. Nutrition, at all stages of life, plays an important role in determining health and wellbeing. METHODS: A roundtable meeting of UK experts on nutrition and ageing considered key aspects of the diet-ageing relationship and developed a consensus position on the main priorities for research and public health actions that are required to help people live healthier lives as they age. RESULTS: The group consensus highlighted the requirement for a life course approach, recognising the multifactorial nature of the impact of ageing. Environmental and lifestyle influences at any life stage are modified by genetic factors and early development. The response to the environment at each stage of life can determine the impact of lifestyle later on. There are no key factors that act in isolation to determine patterns of ageing and it is a combination of environmental and social factors that drives healthy or unhealthy ageing. Too little is known about how contemporary dietary patterns and sedentary lifestyles will impact upon healthy ageing in future generations and this is a priority for future research. CONCLUSIONS: There is good evidence to support change to lifestyle (i.e. diet, nutrition and physical) activity in relation to maintaining or improving body composition, cognitive health and emotional intelligence, immune function and vascular health. Lifestyle change at any stage of life may extend healthy lifespan, although the impact of early changes appears to be greatest.

Can measures of physical performance in mid-life improve the clinical prediction of disability in early old age? Findings from a British birth cohort study.

BACKGROUND: Poor performance in physical tests such as grip strength and walking speed is a risk factor for disability in old age, although whether such measures improve the discrimination of clinical prediction models when traditional clinical risk factors are already known is not clear. The prevalence of disability in mid-life is relatively low and hence screening in this age group may present an opportunity for early identification of those at increased future risk who may benefit most from preventative interventions. METHODS: Data were drawn from two waves of the Medical Research Council National Survey of Health and Development. We examined whether several chronic conditions, poor health behaviours and lower scores on three measures of physical performance (grip strength, chair rise speed and standing balance time) at age 53 were associated with self-reported mobility and/or personal care disability at age 69. We used the area under the curve statistic (AUC) to assess model discrimination. RESULTS: At age 69, 44% (826/1855) of participants reported mobility and/or personal care disability. Our final clinical prediction model included sex, knee osteoarthritis, taking 2+ medications, smoking, increased BMI and poor performance in all three physical tests, with an AUC of 0.740 compared with 0.708 for a model which did not include the performance measures. CONCLUSION: Measures of physical performance in midlife improve discrimination in clinical prediction models for disability over 16 years. Importantly, these and similar measures are also potential targets of future diet, exercise and pharmacological intervention in mid-life.

Socioeconomic inequalities in resilience and vulnerability among older adults: a population-based birth cohort analysis.

ABSTRACTBackground:Aging is associated with declines in physical capability; however, some individuals demonstrate high well-being despite this decline, i.e. they are "resilient." We examined socioeconomic position (SEP) and resilience and the influence of potentially modifiable behavioral resources, i.e. social support and leisure time physical activity (LTPA), on these relationships. METHODS: Data came from the Medical Research Council National Survey of Health and Development, a nationally-representative birth cohort study. Resilience-vulnerability at age 60-64 years (n = 1,756) was operationalized as the difference between observed and expected levels of well-being, captured by the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), given the level of performance-based physical capability. SEP was assessed by father's and own social class, parental education, and intergenerational social mobility. PA and structural/functional social support were reported at ages 53 years and 60-64 years. Path analysis was used to examine mediation of SEP and resilience-vulnerability through LTPA and social support. RESULTS: Participants in the highest social class had scores on the resilience to vulnerability continuum that were an average of 2.3 units (ß = 0.46, 95% CI 0.17, 0.75) higher than those in the lowest social class. Greater LTPA (ß = 0.58, 95% CI 0.31, 0.85) and social support (ß = 3.27, 95% CI 2.90, 3.63) were associated with greater resilience; LTPA partly mediated participant social class and resilience (23.4% of variance). CONCLUSIONS: Adult socioeconomic advantage was associated with greater resilience. Initiatives to increase LTPA may contribute to reducing socioeconomic inequalities in this form of resilience in later life.

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries.

BACKGROUND/OBJECTIVES: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. SUBJECTS/METHODS: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. RESULTS: There were no strong associations between prostate cancer risk and 37 dietary factors. CONCLUSIONS: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.

Work-family life courses and BMI trajectories in three British birth cohorts.

BACKGROUND/OBJECTIVES: Combining work and family responsibilities has previously been associated with improved health in mid-life, yet little is known about how these associations change over time (both biographical and historical) and whether this extends to body mass index (BMI) trajectories for British men and women. The purpose of this study was to investigate relationships between work-family life courses and BMI trajectories across adulthood (16-42 years) for men and women in three British birth cohorts. SUBJECTS/METHODS: Multiply imputed data from three nationally representative British birth cohorts were used-the MRC National Survey of Health and Development (NSHD; 1946 birth cohort, n=3012), the National Child Development Study (NCDS; 1958 birth cohort, n=9614) and the British Cohort Study (BCS; 1970 birth cohort, n=8140). A typology of work-family life course types was developed using multi-channel sequence analysis, linking annual information on work, partnerships and parenthood from 16 to 42 years. Work-family life courses were related to BMI trajectories using multi-level growth models. Analyses adjusted for indicators of prior health, birthweight, child BMI, educational attainment and socioeconomic position across the life course, and were stratified by gender and cohort. RESULTS: Work-family life courses characterised by earlier transitions to parenthood and weaker long-term links to employment were associated with greater increases in BMI across adulthood. Some of these differences, particularly for work-family groups, which are becoming increasingly non-normative, became more pronounced across cohorts (for example, increases in BMI between 16 and 42 years in long-term homemaking women: NSHD: 4.35 kg m-2, 95% confidence interval (CI): 3.44, 5.26; NCDS: 5.53 kg m-2, 95% CI: 5.18, 5.88; BCS: 6.69 kg m-2, 95% CI: 6.36, 7.02). CONCLUSIONS: Becoming a parent earlier and weaker long-term ties to employment are associated with greater increases in BMI across adulthood in British men and women.

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study.

This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. INTRODUCTION: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. METHODS: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0-16 g) worn at the waist for 7 days were classified as low (0.5-1.0 g), medium (1.0-1.5 g) or higher (≥1.5 g) impacts. RESULTS: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [-0.02, 0.08]). CONCLUSIONS: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA.

Operationalising resilience in longitudinal studies: a systematic review of methodological approaches.

Over the life course, we are invariably faced with some form of adversity. The process of positively adapting to adverse events is known as 'resilience'. Despite the acknowledgement of 2 common components of resilience, that is, adversity and positive adaptation, no consensus operational definition has been agreed. Resilience operationalisations have been reviewed in a cross-sectional context; however, a review of longitudinal methods of operationalising resilience has not been conducted. The present study conducts a systematic review across Scopus and Web of Science capturing studies of ageing that posited operational definitions of resilience in longitudinal studies of ageing. Thirty-six studies met inclusion criteria. Non-acute events, for example, cancer, were the most common form of adversity identified and psychological components, for example, the absence of depression, the most common forms of positive adaptation. Of the included studies, 4 used psychometrically driven methods, that is, repeated administration of established resilience metrics, 9 used definition-driven methods, that is, a priori establishment of resilience components and criteria, and 23 used data-driven methods, that is, techniques that identify resilient individuals using latent variable models. Acknowledging the strengths and limitations of each operationalisation is integral to the appropriate application of these methods to life course and longitudinal resilience research.

Menopause, Reproductive Life, Hormone Replacement Therapy, and Bone Phenotype at Age 60-64 Years: A British Birth Cohort.

CONTEXT: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment. OBJECTIVE: The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60-64 years. DESIGN: This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. SETTING: The study was conducted in England, Scotland, and Wales. PARTICIPANTS: Participants included 848 women with a known type of menopause and bone measures at 60-64 years. MAIN OUTCOME MEASURES: Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured. RESULTS: A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%-15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%-11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%-9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%-1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography. CONCLUSIONS: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI and aBMD.

Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development.

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.

Resilience measurement in later life: a systematic review and psychometric analysis.

OBJECTIVES: To systematically review and examine the psychometric properties of established resilience scales in older adults, i.e. ≥60 years. METHODS: A systematic review of Scopus and Web of Science databases was undertaken using the search strategy "resilience" AND (ageing OR aging)". Independent title/abstract and fulltext screening were undertaken, identifying original peer-reviewed English articles that conducted psychometric validation studies of resilience metrics in samples aged ≥60 years. Data on the reliability/validity of the included metrics were extracted from primary studies. RESULTS: Five thousand five hundred nine studies were identified by the database search, 426 used resilience psychometrics, and six psychometric analysis studies were included in the final analysis. These studies conducted analyses of the Connor Davidson Resilience Scale (CD-RISC) and its shortened 10-item version (CD-RISC10), the Resilience Scale (RS) and its shortened 5- (RS-5) and 11- (RS-11) item versions, and the Brief Resilient Coping Scale (BRCS). All scales demonstrated acceptable levels of internal consistency, convergent/discriminant validity and theoretical construct validity. Factor structures for the RS, RS-11 and CD-RISC diverged from the structures in the original studies. CONCLUSION: The RS, RS-5, RS-11, CD-RISC, CD-RISC10 and BRCS demonstrate psychometric robustness adequate for continued use in older populations. However, results from the current study and pre-existing theoretical construct validity studies most strongly support the use of the RS, with modest and preliminary support for the CD-RISC and BRCS, respectively. Future studies assessing the validity of these metrics in older populations, particularly with respect to factor structure, would further strengthen the case for the use of these scales.

Operational Definition of Active and Healthy Ageing (AHA): A Conceptual Framework.

Health is a multi-dimensional concept, capturing how people feel and function. The broad concept of Active and Healthy Ageing was proposed by the World Health Organisation (WHO) as the process of optimizing opportunities for health to enhance quality of life as people age. It applies to both individuals and population groups. A universal Active and Healthy Ageing definition is not available and it may differ depending on the purpose of the definition and/or the questions raised. While the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has had a major impact, a definition of Active and Healthy Ageing is urgently needed. A meeting was organised in Montpellier, France, October 20-21, 2014 as the annual conference of the EIP on AHA Reference Site MACVIA-LR (Contre les Maladies Chroniques pour un Vieillissement Actif en Languedoc Roussillon) to propose an operational definition of Active and Healthy Ageing including tools that may be used for this. The current paper describes the rationale and the process by which the aims of the meeting will be reached.

Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.

BACKGROUND/OBJECTIVES: There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age. SUBJECTS/METHODS: Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests. RESULTS: In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model. CONCLUSIONS: Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Trends in food consumption over 30 years: evidence from a British birth cohort.

BACKGROUND/OBJECTIVES: As populations are ageing, more emphasis is placed on healthy ageing. Over the past decades, food consumption patterns and food availability have also changed drastically, and therefore this study aimed to describe these changes in an ageing population. SUBJECTS/METHODS: Food consumption of participants from the Medical Research Council National Survey on Health and Development, a British birth cohort study, was assessed using a 5-day estimated food records at 60-64 years (2006-11), 53 years (1999), 43 years (1989) and 36 years (1982). Only those who recorded ⩾3 days at all four time points were included in the analyses, n=989 (n=438 men and n=551 women); trends were tested using the Friedman test. RESULTS: Consumption of white bread, whole milk, fats and oils, meat and meat products, alcoholic drinks, coffee, sugar, preserves and confectionery decreased (P<0.001), whereas consumption of wholemeal and granary bread, semi-skimmed milk, fish and fruit and vegetables increased (P<0.001) over time. These observed changes in food consumption reflect a healthier diet, for example, replacement of white bread by granary and wholemeal bread, lower consumption of red and processed meats, somewhat higher consumption of fish, higher consumption of vegetables and lower consumption of coffee. This could partly be because of ageing of the cohort or compliance with dietary recommendations, facilitated by greater availability of healthier foods, such as semi-skimmed milk and wholegrain bread, in the UK. CONCLUSIONS: The changes in food consumption in this British birth cohort over the past three decades are encouraging and reflect a healthier diet in the later years.