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1.  Childhood and Maternal Effects on Physical Health Related Quality of Life Five Decades Later: The British 1946 Birth Cohort 
PLoS ONE  2014;9(3):e88524.
Limited research has been done on the relationships between childhood factors and adult physical health related quality of life, with the underlying pathways not fully elucidated. Data from 2292 participants of the British 1946 birth cohort were used to examine the relationship of childhood characteristics and family environment with principal component summary (PCS) scores and the physical functioning (PF) subscale of the SF-36 at age 60–64 years. Impaired physical functioning was defined as the lowest quartile scores in the PF subscale. Childhood factors (father in manual social class versus non-manual (β =  −2.34; 95%CI: −3.39, −1.28) and poor maternal health versus good/excellent maternal health (β =  −6.18; −8.78, −3.57)) were associated with lower PCS scores at 60–64 years. Adult health behaviours (increasing BMI, lifelong smoking, and lower physical activity) at 53 years were identified as strong risk factors for lower PCS scores. After adjusting for these factors and education level (N = 1463), only poor maternal health remained unattenuated (β =  −5.07; −7.62, −2.51). Similarly poor maternal health doubled the risk of reporting impaired PF (Odds ratio =  2.45; 95%CI: 1.39, 4.30); serious illness in childhood (OR = 1.44; 1.01, 2.06) and lower educational level attained were also risk factors for impaired PF (N = 1526). While findings suggest the influence of father's social class on physical health related quality of life are mediated by modifiable adult social factors and health behaviours; health professionals should also be mindful of the inter-generational risk posed by poor maternal health on the physical health related quality of life of her offspring almost five decades later.
doi:10.1371/journal.pone.0088524
PMCID: PMC3966737  PMID: 24670776
2.  Comparison of the EPIC Physical Activity Questionnaire with Combined Heart Rate and Movement Sensing in a Nationally Representative Sample of Older British Adults 
PLoS ONE  2014;9(2):e87085.
Objectives
To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults.
Methods
Participants aged 60–64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women).
Results
EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (−61.5 to 122.6) and 29.0 (−39.2 to 94.6) kJ/kg/day for PAEE; −4.6 (−10.6 to 1.3) and −6.0 (−10.9 to −1.0) h/day for sedentary time; −171.8 (−454.5 to 110.8) and −60.4 (−367.5 to 246.6) min/day for LPA; 91.1 (−159.5 to 341.8) and 55.4 (−117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho  = 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women).
Conclusion
EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population.
doi:10.1371/journal.pone.0087085
PMCID: PMC3916297  PMID: 24516543
3.  Physical activity levels across adult life and grip strength in early old age: updating findings from a British birth cohort 
Age and Ageing  2013;42(6):794-798.
Introduction: observational studies do not always find positive associations between physical activity and muscle strength despite intervention studies consistently showing that exercise improves strength in older adults. In previous analyses of the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, there was no evidence of an association between leisure time physical activity (LTPA) across adulthood and grip strength at age 53. This study tested the hypothesis that cumulative benefits of LTPA across mid-life on grip strength will have emerged by age 60–64.
Methods: data from the MRC NSHD were used to investigate the associations between LTPA at ages 36, 43, 53 and 60–64 and grip strength at 60–64. Linear regression models were constructed to examine the effect of activity at each age separately and as a cumulative score, including adjustment for potential confounders and testing of life course hypotheses.
Results: there were complete longitudinal data available for 1,645 participants. There was evidence of a cumulative effect of LTPA across mid-life on grip strength at 60–64. Compared with the third of participants who reported the least LTPA participation across the four time points, those in the top third had on average 2.11 kg (95% CI: 0.88, 3.35) stronger grip after adjustments.
Conclusions: increased levels of LTPA across mid-life were associated with stronger grip at age 60–64, in both men and women. As these associations have emerged since age 53, it suggests that LTPA across adulthood may prevent decline in grip strength in early old age.
doi:10.1093/ageing/aft124
PMCID: PMC3809720  PMID: 23981980
physical activity; longitudinal study; grip strength; life course models; older people
4.  How to get started with a systematic review in epidemiology: an introductory guide for early career researchers 
Archives of Public Health  2013;71(1):21.
Background
Systematic review is a powerful research tool which aims to identify and synthesize all evidence relevant to a research question. The approach taken is much like that used in a scientific experiment, with high priority given to the transparency and reproducibility of the methods used and to handling all evidence in a consistent manner.
Early career researchers may find themselves in a position where they decide to undertake a systematic review, for example it may form part or all of a PhD thesis. Those with no prior experience of systematic review may need considerable support and direction getting started with such a project. Here we set out in simple terms how to get started with a systematic review.
Discussion
Advice is given on matters such as developing a review protocol, searching using databases and other methods, data extraction, risk of bias assessment and data synthesis including meta-analysis. Signposts to further information and useful resources are also given.
Conclusion
A well-conducted systematic review benefits the scientific field by providing a summary of existing evidence and highlighting unanswered questions. For the individual, undertaking a systematic review is also a great opportunity to improve skills in critical appraisal and in synthesising evidence.
doi:10.1186/0778-7367-71-21
PMCID: PMC3844862  PMID: 23919540
Systematic review; Systematic review methods; Meta-analysis; Early career researchers; Evidence synthesis; Observational studies
5.  Telomere Length and Physical Performance at Older Ages: An Individual Participant Meta-Analysis 
PLoS ONE  2013;8(7):e69526.
Background
Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.
Methods
Using data from four UK adult cohorts (ages 53–80 years at baseline), we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured using walking and chair rise speed, standing balance time and grip strength. Telomere length was measured by quantitative real-time polymerase chain reaction (PCR) in whole blood at baseline and follow-up (time 1, time 2).
Results
Total sample sizes in meta-analyses ranged from 1,217 to 3,707. There was little evidence that telomere length was associated with walking speed, balance or grip strength, though weak associations were seen with chair rise speed and grip strength at baseline (p = 0.02 and 0.01 respectively). Faster chair rise speed at follow-up, was associated with a smaller decline in telomere length between time 1 and time 2 (standardised coefficient per SD increase 0.061, 95% CI 0.006, 0.115, p = 0.03) but this was consistent with chance (p = 0.08) after further adjustment.
Conclusions
Whereas shortening of leukocyte telomeres might be an important measure of cellular ageing, there is little evidence that it is a strong biomarker for physical performance.
doi:10.1371/journal.pone.0069526
PMCID: PMC3724915  PMID: 23922731
6.  Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme 
PLoS ONE  2013;8(7):e70045.
Background
The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability.
Results
We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score = −0.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.
Conclusion
Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
doi:10.1371/journal.pone.0070045
PMCID: PMC3720952  PMID: 23894584
7.  The Bidirectional Association between Depressive Symptoms and Gait Speed: Evidence from the English Longitudinal Study of Ageing (ELSA) 
PLoS ONE  2013;8(7):e68632.
Background
Depressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.
Methods
We used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002–03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ≥4 on the eight-item Center for Epidemiological Studies-Depression scale).
Results
Slower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (β regression coefficient [β] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (β -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.011, 95% CI, -0.021 to -0.001).
Conclusions
The inverse association between gait speed and depressive symptoms appears to be bidirectional.
doi:10.1371/journal.pone.0068632
PMCID: PMC3706406  PMID: 23874698
8.  Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts 
Age  2013;36(1):445-456.
Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS) 5 to 10 years later. Data were drawn from five British cohorts participating in the Healthy Ageing across the Life Course research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10 % of a standard deviation (three studies, N = 3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-013-9553-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-013-9553-8
PMCID: PMC3818137  PMID: 23818103
Physical capability; Positive mental wellbeing; Grip strength; Walking speed; Chair rise time
9.  Genetic Variants Influencing Biomarkers of Nutrition Are Not Associated with Cognitive Capability in Middle-Aged and Older Adults123 
The Journal of Nutrition  2013;143(5):606-612.
Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
doi:10.3945/jn.112.171520
PMCID: PMC3738233  PMID: 23468552
10.  Menopausal Characteristics and Physical Functioning in Older Adulthood in the NHANES III 
Menopause (New York, N.y.)  2012;19(3):283-289.
Objective
We hypothesized that natural menopause would be related to better physical functioning compared to surgical menopause and that later age at menopause would be related to better physical functioning.
Methods
Our sample comprised 1765 women aged ≥ 60 years who participated in the National Health and Nutrition Examination Survey III, a cross-sectional study representative of the United States population. Women recalled age at final menstrual period and age at removal of the uterus and ovaries and reported age, race and ethnicity, height, weight, educational attainment, smoking status, number of children, and use of estrogen therapy. Respondents completed a walk trial and chair rises and reported functional limitations.
Results
Women with a surgical menopause had chair rise times that were an average of 4.4% slower than those of women with natural menopause (95% CI 0.56, 8.27). Women with natural menopause at age ≥ 55 years had an average walking speed 0.05 meters/second (95% CI 0.01, 0.10) faster than women with natural menopause at age < 45 years. Later ages at natural and surgical menopause were also related to lower self-reported functional limitation. Women with surgical menopause at age ≥ 55 years had odds of functional limitation 0.52 times (95% CI 0.29, 0.95) those of women with surgical menopause at age < 40 years, with similar patterns for natural menopause.
Conclusions
Women with surgical menopause and earlier age at menopause had worse physical function in older adulthood. These groups of women may benefit from interventions to prevent functional decline.
doi:10.1097/gme.0b013e3182292b06
PMCID: PMC3258455  PMID: 21993081
menopause; physical functioning; women’s health
11.  Body Mass Index, Muscle Strength and Physical Performance in Older Adults from Eight Cohort Studies: The HALCyon Programme 
PLoS ONE  2013;8(2):e56483.
Objective
To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Methods
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Results
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Conclusion
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
doi:10.1371/journal.pone.0056483
PMCID: PMC3577921  PMID: 23437142
12.  The Dynamic Relationship Between Physical Function and Cognition in Longitudinal Aging Cohorts 
Epidemiologic Reviews  2013;35(1):33-50.
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.
doi:10.1093/epirev/mxs004
PMCID: PMC3578448  PMID: 23349427
aging; cognition; correlated change; longitudinal analysis; meta-analysis; physical functioning; systematic review
13.  Type and Timing of Menopause and Later Life Mortality Among Women in the Iowa Established Populations for the Epidemiological Study of the Elderly Cohort 
Journal of Women's Health  2012;21(1):10-16.
Abstract
Background
The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause.
Methods
Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality.
Results
A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause ≥55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables.
Conclusions
Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times.
doi:10.1089/jwh.2011.2745
PMCID: PMC3256559  PMID: 21970557
14.  Genetic markers of bone and joint health and physical capability in older adults: the HALCyon programme 
Bone  2013;52(1):278-285.
Background
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Results
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
Conclusion
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
Highlights
► We examined associations between bone-related genotypes and physical capability. ► We conducted a meta-analysis on 12,836 middle-age adults. ► We found CASR may be associated with grip strength. ► No substantial support for specific bone mineral density variants and physical capability.
doi:10.1016/j.bone.2012.10.004
PMCID: PMC3526776  PMID: 23072920
BMD, bone mineral density; OA, osteoarthritis; BMI, body mass index; SNP, single nucleotide polymorphism; CaPS, Caerphilly Prospective Study; ELSA, English Longitudinal Study of Ageing; HAS, Hertfordshire Ageing Study; HCS, Hertfordshire Cohort Study; LBC1921, The Lothian Birth Cohort 1921; NSHD, National Survey of Health and Development; HWE, Hardy–Weinberg equilibrium; WHR, waist–hip ratio; GWAS, genome-wide association studies; Aging; Grip strength; Calcium; Bone mineral density; Osteoarthritis
15.  Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis 
Psychoneuroendocrinology  2013;38(1):40-49.
Summary
The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
doi:10.1016/j.psyneuen.2012.04.016
PMCID: PMC3533133  PMID: 22658392
HPA axis; Physical capability; Healthy ageing
16.  Gender and Life Course Occupational Social Class Differences in Trajectories of Functional Limitations in Midlife: Findings From the 1946 British Birth Cohort 
Background.
Older women and those of lower socioeconomic position (SEP) consistently constitute a larger portion of the disabled population than older men or those of higher SEP, yet no studies have examined when in the life course these differences emerge.
Methods.
Prevalence of self-reported limitations in the upper body (gripping or reaching) and lower body (walking or stair climbing) at 43 and 53 years were utilized from 1,530 men and 1,518 women from the British 1946 birth cohort. Generalized linear models with a binomial distribution were used to examine the effects of gender, childhood and adult SEP, and the differences in the SEP effects by gender on the prevalence of limitations at age 43 years and changes in prevalence from 43 to 53 years.
Results.
For both genders, the prevalence of upper and lower body limitations were reported at 3%–5% at age 43 years. However, by age 53 years, women’s upper body limitations had increased to 28% and lower body limitations to 21%, whereas men’s limitations had only increased to 12% and 11%, respectively. Men and women whose father’s occupation was manual or whose adult head of household occupation was manual had higher prevalence of both limitations compared with those with non-manual backgrounds. These differences widened with age, especially in women. The effect of adult SEP on the prevalence of limitations was stronger than that of childhood SEP and was partly mediated by educational attainment.
Conclusion.
Our findings provide the first evidence that prevention of disability in old age should begin early in midlife, especially for women from manual occupation households.
doi:10.1093/gerona/glr139
PMCID: PMC3210957  PMID: 21860018
Gender; Social class; Functional limitations; Longitudinal studies; Middle aged
17.  ACTN3 genotype, athletic status and lifecourse physical capability: meta-analysis of the published literature and findings from nine studies 
Human mutation  2011;32(9):1008-1018.
The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, though not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For lifecourse physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (p-value=0.09, n=7672 in males; p-value=0.90, n=7839 in females), standing balance, timed get up and go or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population.
doi:10.1002/humu.21526
PMCID: PMC3174315  PMID: 21542061
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
18.  ACTN3 Genotype, Athletic Status, and Life Course Physical Capability: Meta-Analysis of the Published Literature and Findings from Nine Studies 
Human Mutation  2011;32(9):1008-1018.
The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population. Hum Mutat 32:1–11, 2011. © 2011 Wiley-Liss, Inc.
doi:10.1002/humu.21526
PMCID: PMC3174315  PMID: 21542061
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
19.  Cognitive Function in Childhood and Lifetime Cognitive Change in Relation to Mental Wellbeing in Four Cohorts of Older People 
PLoS ONE  2012;7(9):e44860.
Background
Poorer cognitive ability in youth is a risk factor for later mental health problems but it is largely unknown whether cognitive ability, in youth or in later life, is predictive of mental wellbeing. The purpose of this study was to investigate whether cognitive ability at age 11 years, cognitive ability in later life, or lifetime cognitive change are associated with mental wellbeing in older people.
Methods
We used data on 8191 men and women aged 50 to 87 years from four cohorts in the HALCyon collaborative research programme into healthy ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the National Child Development Survey, and the MRC National Survey for Health and Development. We used linear regression to examine associations between cognitive ability at age 11, cognitive ability in later life, and lifetime change in cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale and meta-analysis to obtain an overall estimate of the effect of each.
Results
People whose cognitive ability at age 11 was a standard deviation above the mean scored 0.53 points higher on the mental wellbeing scale (95% confidence interval 0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89 points (0.72, 1.07). A standard deviation improvement in cognitive ability in later life relative to childhood ability was associated with 0.66 points (0.39, 0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a standard deviation in mental wellbeing score. Adjustment for potential confounding and mediating variables, primarily the personality trait neuroticism, substantially attenuated these associations.
Conclusion
Associations between cognitive ability in childhood or lifetime cognitive change and mental wellbeing in older people are slight and may be confounded by personality trait differences.
doi:10.1371/journal.pone.0044860
PMCID: PMC3438162  PMID: 22970320
20.  Adult macronutrient intake and physical capability in the MRC National Survey of Health and Development 
Age and Ageing  2012;42(1):81-87.
Background: poor physical capability is associated with higher subsequent risk of disability and mortality in older people. Energy and macronutrient intakes may play a role in the maintenance of physical capability. This analysis aimed to examine the role of intakes of energy and the macronutrients, protein, carbohydrate and fat in early and mid-adulthood on objective measures of physical capability in later adulthood in the MRC National Survey of Health and Development (1946 British birth cohort).
Methods: adult diet assessed by a 5-day diary at 36 years (1982) and 43 years (1989). Physical capability was assessed at 53 years. Objective measures were height, weight and three measures of physical capability: grip strength, standing balance time and chair rises.
Results: using multiple linear regression analysis, modest positive associations were found between energy intake at 36 and 43 years and grip strength at 53 years. Results for macronutrients were mixed although there was some indication of relationships of protein intake with grip strength and standing balance time.
Conclusions: higher energy intake in midlife may play a role in the prevention of muscle weakness in later life. Higher protein intakes may also be related to physical capability but further research is needed.
doi:10.1093/ageing/afs101
PMCID: PMC3518903  PMID: 22923606
physical capability; diet; energy; macronutrients; longitudinal
21.  Lifetime Occupational Physical Activity and Musculoskeletal Aging in Middle-Aged Men and Women in Denmark: Retrospective Cohort Study Protocol and Methods 
JMIR Research Protocols  2012;1(2):e7.
Background
Physical function is essential for performing most aspects of daily life and musculoskeletal aging leads to a decline in physical function. The onset and rate of this process vary and are influenced by environmental, genetic, and hormonal factors. Although everyone eventually experiences musculoskeletal aging, it is beneficial to study the factors that influence the aging process in order to prevent disability. The role of occupational physical activity in the musculoskeletal aging process is unclear. In the past, hard physical work was thought to strengthen the worker, but current studies in this field fail to find a training effect in jobs with a high level of occupational physical activity.
Objective
The aim of this study is to examine the influence of lifetime occupational physical activity on physical function in midlife. The study follows the “occupational life-course perspective,” emphasizing the importance of occupational exposures accumulated throughout life on the musculoskeletal aging process taking socioeconomic and lifestyle factors into consideration.
Methods
This study is a retrospective cohort study including a cross-sectional measurement of physical function in 5000 middle-aged Danes. Data was obtained from the Copenhagen Aging and Midlife Biobank (CAMB) which is based on three existing Danish cohorts. Using questionnaire information about the five longest-held occupations, the job history was coded from the Danish version of the International Standard Classification of Occupations (D-ISCO 88) and a job exposure matrix containing information about occupational physical activity in Danish jobs was applied to the dataset. The primary outcomes are three tests of physical function: handgrip strength, balance, and chair rise. In the analyses, we will compare physical function in midlife according to accumulated exposure to high levels of occupational physical activity.
Conclusions
We have a unique opportunity to study the influence of work on early musculoskeletal aging taking other factors into account. In this study, the “healthy worker effect” is reduced due to inclusion of people from the working population and people who are already retired or have been excluded from the labor market. However, low participation in the physical tests can lead to selection bias.
doi:10.2196/resprot.2191
PMCID: PMC3626163  PMID: 23611836
Occupational exposure; work load; physical fitness; musculoskeletal system; aging
22.  Absence of association of a SNP in the TERT-CLPTM1L locus with age-related phenotypes in a large multi-cohort study: the HALCyon program 
Aging cell  2011;10(3):520-532.
Summary
Background
Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other ageing traits such as physical capability have not been reported.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from 9 UK cohorts were genotyped for the single nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses.
Results
No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score=0.02, 95% CI: -0.01- 0.04, p-value=0.12, n=18,737), physical performance tests (e.g. pooled beta for grip strength=-0.02, 95% CI:-0.045- 0.006, p-value=0.14, n=11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment.
Conclusion
The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multi-cohort study suggests that whilst this SNP may be associated with cancer, it is not an important contributor to other markers of ageing.
doi:10.1111/j.1474-9726.2011.00687.x
PMCID: PMC3094481  PMID: 21332924
Aging; ageing; middle-aged; telomere; cognition; physical
23.  Population heterogeneity in trajectories of midlife blood pressure 
Epidemiology (Cambridge, Mass.)  2012;23(2):203-211.
Background
We investigated whether there are subgroups with different underlying (latent) trajectories of midlife systolic blood pressure (BP), diastolic BP and pulse pressure in a UK cohort.
Methods
Data are from 1840 men and 1819 women with BP measured at age 36, 43 and 53years. We used unconditional growth mixture models to test for the presence of latent trajectory classes. Extracted classes were described in terms of a number of known lifetime risk factors, and linked to the risk of undiagnosed angina (Rose questionnaire) at age 53 years.
Results
In both sexes for systolic BP, diastolic BP and pulse pressure, there was a large “normative” class (>90% of the sample) characterized by gentle annual increases (eg an increase in male systolic BP of 0.9mmHg/year [95% confidence interval = 0.9 to1.0]), with a smaller class for whom the rate of increase was high (e.g. an increase in male systolic BP of 3.1mmHg/year [2.8 to3.4]). In women there was an additional class for whom BP was high at age 36 and remained high. Persons in the “normative” classes were, on average, heavier at birth and taller at age 7 years, had a lower midlife body mass index, and were less likely to be on antihypertensive medication compared with those in other classes. Among those with no diagnosed cardiovascular disease, those in the classes with more strongly increasing systolic BP and pulse pressure were at greatest risk of angina.
Conclusion
Our study suggests that in midlife the majority of the population have a gentle underlying increase in BP, but that there also exists an important subgroup in whom BP increases much more markedly. These classes may be useful for identifying those most at risk of cardiovascular disease.
doi:10.1097/EDE.0b013e3182456567
PMCID: PMC3355297  PMID: 22249241
24.  Early life circumstances and their impact on menarche and menopause 
Women's health (London, England)  2009;5(2):175-190.
Ages at menarche and menopause have been shown to be associated with adverse health outcomes in later life. For example, earlier menarche and later menopause have been independently linked to higher risk of breast cancer. Earlier menarche may also be associated with an increased risk of endometrial cancer, menstrual problems and adult obesity. Given the associations of ages at menarche and menopause with future health outcomes, it is important to establish what factors across life, and generations, may influence these. This article examines the associations of early life factors, namely birthweight, bodyweight and growth during childhood, childhood socioeconomic circumstances and psychosocial factors with ages at menarche and menopause. It examines possible explanations of the associations found, including life history theory, and discusses areas for future research.
doi:10.2217/17455057.5.2.175
PMCID: PMC3287288  PMID: 19245355
early life; life course; life history theory; menarche; menopause; reproductive health
25.  Is chair rise performance a useful measure of leg power? 
Background and Aims
Chair rise performance, which is simple to assess in a home or clinic setting, has been used as a method of predicting leg power deficit in older adults. More recently chair rise performance has been assessed in younger populations as a baseline for assessment of subsequent age-related declines in function and power. However, as rising from a chair repeatedly not only requires lower limb strength and power but also good balance and coordination, it may not be purely a measure of leg power especially among these younger, well functioning groups who are yet to experience age-related declines and deficits in function. The aim of this study was to assess whether chair rise performance can be considered as a predictor of leg power, and hence of deficits in this, in men and women in mid-life. We assessed the relationship of chair rise performance with leg extensor power (LEP) measured using the Nottingham Power Rig (NPR), and with standing balance performance.
Methods
LEP was measured in a clinic setting in a sub-sample of 81 men and 93 women from the MRC National Survey of Health and Development, a nationally representative cohort born in Britain in 1946. The time taken to rise from a chair 10 times and standing balance time were assessed during home visits at the same age.
Results
Increasing LEP was associated with better chair rise performance among those who completed 10 chair rises in ≥15 seconds, after adjustment for body size (p=0.008). Better standing balance performance was associated with better chair rise performance in men, but not women.
Conclusions
That LEP and standing balance are both related to chair rise time in men suggests that chair rise time should not be thought of purely as a proxy measure of leg power in middle-aged populations. This has implications for longitudinal studies which want to study age-related decline in chair rise performance.
PMCID: PMC3260651  PMID: 21422795
physical performance; standing balance; leg extensor power; chair rises

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