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1.  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
2.  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
3.  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
4.  The physical capability of community-based men and women from a British cohort: the European Prospective Investigation into Cancer (EPIC)-Norfolk study 
BMC Geriatrics  2013;13:93.
Background
The European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (≤0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study.
Methods
In the European Prospective Investigation into Cancer-Norfolk study, 8,623 community-based adults (48-92 years old) underwent assessment of grip strength, walking speed, timed chair stands and standing balance. The proportion of older men and women (≥65 years) fulfilling EWGSOP criteria for muscle mass measurement was estimated. Additionally, cross-sectional associations of physical capability with age and sex were explored using linear and logistic regression.
Results
Approximately 1 in 4 older participants (28.8%) fulfilled criteria for muscle mass measurement with a greater proportion of women than men falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7) weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem stand for 10 seconds than men, although usual walking speed was similar. Physical capability was inversely associated with age and per year, walking speed decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this, there was still variation within age-groups and not all older people had low physical capability.
Conclusions
Every effort to optimise functional health in later life should be made since poor function is not inevitable. However, if the EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older people could qualify for muscle mass measurement which is not commonly available. Considering population ageing, further discussion is needed over the utility of muscle mass measurement in clinical practice.
doi:10.1186/1471-2318-13-93
PMCID: PMC3846689  PMID: 24020915
Ag(e)ing; Sarcopenia; Hand strength; Physical capability; Sex factors
5.  Objectively measured physical capability levels and mortality: systematic review and meta-analysis 
Objective To do a quantitative systematic review, including published and unpublished data, examining the associations between individual objective measures of physical capability (grip strength, walking speed, chair rising, and standing balance times) and mortality in community dwelling populations.
Design Systematic review and meta-analysis.
Data sources Relevant studies published by May 2009 identified through literature searches using Embase (from 1980) and Medline (from 1950) and manual searching of reference lists; unpublished results were obtained from study investigators.
Study selection Eligible observational studies were those done in community dwelling people of any age that examined the association of at least one of the specified measures of physical capability (grip strength, walking speed, chair rises, or standing balance) with mortality.
Data synthesis Effect estimates obtained were pooled by using random effects meta-analysis models with heterogeneity between studies investigated.
Results Although heterogeneity was detected, consistent evidence was found of associations between all four measures of physical capability and mortality; those people who performed less well in these tests were found to be at higher risk of all cause mortality. For example, the summary hazard ratio for mortality comparing the weakest with the strongest quarter of grip strength (14 studies, 53 476 participants) was 1.67 (95% confidence interval 1.45 to 1.93) after adjustment for age, sex, and body size (I2=84.0%, 95% confidence interval 74% to 90%; P from Q statistic <0.001). The summary hazard ratio for mortality comparing the slowest with the fastest quarter of walking speed (five studies, 14 692 participants) was 2.87 (2.22 to 3.72) (I2=25.2%, 0% to 70%; P=0.25) after similar adjustments. Whereas studies of the associations of walking speed, chair rising, and standing balance with mortality have only been done in older populations (average age over 70 years), the association of grip strength with mortality was also found in younger populations (five studies had an average age under 60 years).
Conclusions Objective measures of physical capability are predictors of all cause mortality in older community dwelling populations. Such measures may therefore provide useful tools for identifying older people at higher risk of death.
doi:10.1136/bmj.c4467
PMCID: PMC2938886  PMID: 20829298
6.  Physical capability in mid-life and survival over 13 years of follow-up: British birth cohort study 
Objectives To examine associations between three commonly used objective measures of physical capability assessed at age 53 and a composite score of these measures and all cause mortality; to investigate whether being unable to perform these tests is associated with mortality.
Design Cohort study.
Setting MRC National Survey of Health and Development in England, Scotland, and Wales.
Participants 1355 men and 1411 women with data on physical capability at age 53 who were linked to the National Health Service (NHS) central register for death notification.
Main outcome measure All cause mortality between ages 53 (1999) and 66 (2012).
Results For each of the three measures of physical capability (grip strength, chair rise speed, and standing balance time) those participants unable to perform the test and those in the lowest performing fifth were found to have higher mortality rates than those in the highest fifth. Adjustment for baseline covariates partially attenuated associations but in fully adjusted models the main associations remained. For example, the fully adjusted hazard ratio of all cause mortality for the lowest compared with the highest fifth of a composite score of physical capability was 3.68 (95% confidence interval 2.03 to 6.68). Those people who could not perform any of the tests had considerably higher rates of death compared with those people able to perform all three tests (8.40, 4.35 to 16.23). When a series of models including different combinations of the measures were compared by using likelihood ratio tests, all three measures of physical capability were found to improve model fit, and a model including all three measures produced the highest estimate of predictive ability (Harrell’s C index 0.71, 95% confidence interval 0.65 to 0.77). There was some evidence that standing balance time was more strongly associated with mortality than the other two measures.
Conclusions Lower levels of physical capability at age 53 and inability to perform capability tests are associated with higher rates of mortality. Even at this relatively young age these measures identify groups of people who are less likely than others to achieve a long and healthy life.
doi:10.1136/bmj.g2219
PMCID: PMC4004787  PMID: 24787359
7.  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
8.  A life-course approach to healthy ageing: maintaining physical capability 
Research on healthy ageing lacks an agreed conceptual framework and has not adequately taken into account the growing evidence that social and biological factors from early life onwards affect later health. We conceptualise healthy ageing within a life-course framework, separating healthy biological ageing (in terms of optimal physical and cognitive functioning, delaying the onset of chronic diseases, and extending length of life for as long as possible) from changes in psychological and social wellbeing. We summarise the findings of a review of healthy ageing indicators, focusing on objective measures of physical capability, such as tests of grip strength, walking speed, chair rises and standing balance, which aim to capture physical functioning at the individual level, assessing the capacity to undertake the physical tasks of daily living. There is robust evidence that higher scores on these measures are associated with lower rates of mortality, and more limited evidence of lower risk of morbidity, and of age-related patterns of change. Drawing on a research collaboration of UK cohort studies, we summarise what is known about the influences on physical capability in terms of lifetime socioeconomic position, body size and lifestyle, and underlying physiology and genetics; the evidence to date supports a broad set of factors already identified as risk factors for chronic diseases. We identify a need for larger longitudinal studies to investigate age-related change and ethnic diversity in these objective measures, the dynamic relationships between them, and how they relate to other component measures of healthy ageing. Robust evidence across cohort studies, using standardised measures within a clear conceptual framework, will benefit policy and practice to promote healthy ageing.
doi:10.1017/S0029665113003923
PMCID: PMC3981474  PMID: 24456831
Life course; Epidemiology; Healthy ageing; Physical capability; Cohort studies
9.  Evaluation of Factors Influencing Grip Strength in Elderly Koreans 
Journal of Bone Metabolism  2012;19(2):103-110.
Objectives
Grip strength has been used as a measure of function in various health-related conditions. Although grip strength is known to be affected by both physical and psychological factors, few studies have looked at those factors comprehensively in a population-based cohort regarding elderly Koreans. The aim of this study was to evaluate potential factors influencing grip strength in elderly Koreans.
Methods
We evaluated dominant hand grip strengths in 143 men and 123 women older than 65 years who participated in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA). Individuals who had a history of surgery for musculoskeletal disease or trauma in the upper extremity were excluded. Factors assessed for potential association with grip strength were; 1) demographics such as age and gender, 2) body constructs such as height, body mass index (BMI), and bone mineral density (BMD), 3) upper extremity functional status using disabilities of the arm, shoulder and hand (DASH) scores, and 4) mental health status using a depression scale and the short form-36 (SF36) mental health score. Multivariate analyses were performed in order to identify factors independently associated with grip strength.
Results
Grip strengths of dominant hands in elderly Koreans were found to generally decrease with aging, and were significantly different between men and women, as expected. Multivariate analyses indicated that grip strength was independently associated with age, height and BMI in men (R2 = 21.3%), and age and height (R2 = 19.7%) in women. BMD, upper extremity functional status, or mental health status were not found to be associated with grip strength.
Conclusions
This study demonstrates that in elderly Koreans, grip strength is mainly influenced by age and height in both men and women, and additionally by BMI in men. BMD or self-reported physical or mental health status was not found to influence grip strength in elderly Koreans. This information may be helpful in future studies using grip strength as a measure of function in elderly Koreans.
doi:10.11005/jbm.2012.19.2.103
PMCID: PMC3780925  PMID: 24524040
Factors; Grip strength; Influence; Koreans
10.  ASSOCIATION OF TESTOSTERONE AND ESTRADIOL WITH AGE-RELATED DECLINES IN PHYSICAL FUNCTION IN A DIVERSE SAMPLE OF MEN 
Objectives
To examine the association between aging and physical function in men by testing a theoretically-based model of aging, hormones, body composition, strength, and physical function with data obtained from men enrolled in the Boston Area Community Health/Bone (BACH/Bone) Survey.
Design
Cross-sectional, observational survey.
Setting
Population-based
Participants
810 Black, Hispanic, and White Boston randomly-selected men ages of 30–79 y.
Measurements
Testosterone, estradiol, sex hormone-binding globulin, lean and fat mass, grip strength, and summated index of physical function (derived from walk and chair stand tests).
Results
Measures of grip strength and physical function declined strongly associated with age. For instance, 10 y of aging was associated with a 0.49-point difference (scale: 0–7) in physical function. Age differences in total testosterone and estradiol concentrations were smaller than age differences in their free fractions. Weak or non-significant age-adjusted correlations were observed between hormones and measures of physical function. Path analysis, however, revealed a positive association between testosterone and appendicular lean mass, and a strong negative association between testosterone and total fat mass. Lean and fat mass, in turn, were strongly associated with grip strength and physical function, indicating the possibility of testosterone influencing physical function via indirect associations with body composition.
Conclusions
The age-related decline in serum testosterone concentration in men has a relatively weak association with physical strength and functional outcomes via its associations with lean and fat mass.
doi:10.1111/j.1532-5415.2008.01965.x
PMCID: PMC2787197  PMID: 19016935
aging; androgens; body composition; estrogens; men; physical function; population studies
11.  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
12.  Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme 
Aging Cell  2011;10(3):520-532.
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 aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine 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. 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 to 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 to 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. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging.
doi:10.1111/j.1474-9726.2011.00687.x
PMCID: PMC3094481  PMID: 21332924
aging; cognition; middle-aged; physical; telomere
13.  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
14.  Area Deprivation Across the Life Course and Physical Capability in Midlife: Findings From the 1946 British Birth Cohort 
American Journal of Epidemiology  2013;178(3):441-450.
Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, −7.4% (95% confidence interval (CI): −12.8, −2.8); chair rise, 2.1% (95% CI: −0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (−5.1%, 95% CI: −8.7, −1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals—for standing balance, as early as childhood.
doi:10.1093/aje/kwt003
PMCID: PMC3727343  PMID: 23788665
geography; Great Britain; health status disparities; longitudinal studies; multilevel analysis; physical endurance; residence characteristics; socioeconomic factors
15.  Menopausal status and physical performance in midlife: findings from a British birth cohort study 
Menopause (New York, N.Y.)  2008;15(6):1079-1085.
Objective
To test the associations of menopausal status, timing of menopause and hysterectomy with physical performance at age 53y
Design
Using data on women participating in the MRC National Survey of Health and Development who have been followed up since birth in March 1946 (N=1386) associations of interest were examined. Menopausal status, grip strength, chair rises and standing balance time were assessed at age 53y and covariates were measured across life.
Results
Women who were post-menopausal and not using hormone replacement therapy (HT) at age 53y had lower mean grip strength than women who were still pre- or peri-menopausal at this age. However, this trend of decreasing grip strength across the three natural menopausal categories (from pre- to post-menopausal) was explained by current body size. Those women who had undergone hysterectomy before age 40y had significantly weaker grip strength than women who had undergone hysterectomy at later ages - in fully adjusted analyses those women who had a hysterectomy before age 40y had a mean grip strength 5.21kg (95% CI: 2.18, 8.25) lower than women who had a hysterectomy between ages 50 and 53y. There were no significant associations between menopausal status or age at hysterectomy and chair rise or standing balance time and also no significant associations between timing of menopause and any of the performance measures.
Conclusions
Women who have hysterectomies at young ages represent a group who may require more support than other women to achieve and maintain good physical performance, especially muscle strength, in mid-life.
doi:10.1097/gme.0b013e31816f63a3
PMCID: PMC3182533  PMID: 18520694
menopause; hysterectomy; grip strength; chair rises; standing balance; physical performance
16.  The association between dehydroepiandosterone and frailty in older men and women 
Age and Ageing  2009;38(4):401-406.
Objectives: to evaluate the association between dehydroepiandosterone (DHEA) and physical frailty in older adults.
Design: cross-sectional analysis of baseline information from three separate studies in healthy older men, women and residents of assisted living.
Setting: academic health centre in greater Hartford, CT, USA.
Participants: eight hundred and ninety-eight adults residing in the community or assisted living facility.
Measurements: participants had measurement of frailty (weight loss, grip strength, sense of exhaustion, walking speed and physical activity) and serum DHEAS levels.
Results: overall, 6% of the individuals in the study were classified as frail, 58% intermediate frail and 35% were not frail. In the bivariate analysis, there were differences between categories of frailty across age, gender and by DHEAS levels. In an ordinal logistic regression model, with frailty as a dependent measure, we found that age, DHEAS and interactions of age and BMI and DHEAS and BMI were predictive of more frailty characteristics.
Conclusion: we found an association between frailty and DHEAS levels. Whether the association is due to similar conditions resulting in lower DHEA levels and more susceptibility to frailty or whether lower DHEA levels have an impact on increasing frailty cannot be addressed by cross-sectional analysis. Gender did not impact the association between DHEAS and frailty, but obesity (BMI > 30 kg/m2) attenuated the association between higher DHEA levels and lower frailty status.
doi:10.1093/ageing/afp015
PMCID: PMC2720687  PMID: 19276095
dehydroepiandosterone; frailty; ageing; elderly
17.  Physical Activity Across Adulthood and Physical Performance in Midlife 
Background
Evidence, mainly from cross-sectional studies, suggests that physical activity is a potentially important modifiable factor associated with physical performance and strength in older age. It is unclear whether the benefits of physical activity accumulate across life or whether there are sensitive periods when physical activity is more influential.
Purpose
To examine the associations of leisure-time physical activity across adulthood with physical performance and strength in midlife, and to test whether there are cumulative benefits of physical activity.
Methods
Using data on approximately 2400 men and women from the UK Medical Research Council National Survey of Health and Development, followed up since birth in March 1946, the associations of physical activity levels during leisure time self-reported prospectively at ages 36, 43, and 53 years with grip strength, standing balance, and chair rise times, assessed by nurses at age 53 years (in 1999), were examined in 2010.
Results
There were independent positive effects of physical activity at all three ages on chair rise performance, and at ages 43 and 53 years on standing balance performance, even after adjusting for covariates. These results were supported by evidence of cumulative effects found when using structured life course models. Physical activity and grip strength were not associated in women and, in men, only physical activity at age 53 years was associated with grip strength.
Conclusions
There are cumulative benefits of physical activity across adulthood on physical performance in midlife. Increased activity should be promoted early in adulthood to ensure the maintenance of physical performance in later life.
doi:10.1016/j.amepre.2011.06.035
PMCID: PMC3185208  PMID: 21961464
18.  Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis 
PLoS ONE  2011;6(1):e15564.
Background
Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.
Methods and Findings
Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.
Conclusions
Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.
doi:10.1371/journal.pone.0015564
PMCID: PMC3027621  PMID: 21297868
19.  Hyperkyphotic Posture and Poor Physical Functional Ability in Older Community-Dwelling Men and Women: The Rancho Bernardo Study 
Background
Physical functional decline is often the determining factor that leads to loss of independence in older persons. Identifying risk factors for physical disability may lead to interventions that may prevent or delay the onset of functional decline. Our study objective was to determine the association between hyperkyphotic posture and physical functional limitations.
Methods
Participants were 1578 older men and women from the Rancho Bernardo Study who had kyphotic posture measured as the distance from the occiput to table (units = 1.7-cm blocks, placed under the participant’s head when lying supine on a radiology table). Self-reported difficulty in bending, walking, and climbing was assessed by standard questionnaires. Physical performance was assessed by measuring grip strength and ability to rise from a chair without the use of the arms.
Results
Men were more likely to be hyperkyphotic than were women (p < .0001). In multiply adjusted comparisons, there was a graded stepwise increase in difficulty in bending, walking and climbing, measured grip strength, and ability to rise from a chair. For example, the odds ratio (OR) of having to use the arms to stand up from a chair increased from 1.6 (95% confidence interval [CI]: 0.9–3.0) for individuals defined as hyperkyphotic by 1 block to 2.9 (95% CI: 1.7–5.1) for individuals defined as hyperkyphotic by 2 blocks to 3.7 (95% CI: 2.1–6.3) for individuals defined as hyperkyphotic by ≥ 3 blocks compared to those who were not hyperkyphotic (p for trend < .0001).
Conclusions
Older persons with hyperkyphotic posture are more likely to have physical functional difficulties.
PMCID: PMC1360196  PMID: 15972617
20.  Statins, Angiotensin-Converting Enzyme Inhibitors and Physical Performance in Older Women 
OBJECTIVES
Angiotensin-converting enzyme (ACE) inhibitor and statin medications may preserve skeletal muscle. We examined associations between each medication class and baseline and mean annual change in physical performance measures and muscle strength in older women.
DESIGN
Prospective cohort study
PARTICIPANTS
Participants from the Women’s Health Initiative Clinical Trials who were aged 65–79 at baseline and had physical performance measures, self-report of health insurance and no prior history of stroke or congestive heart failure were included (n=5777). Women were recruited between 1993 and 1998.
MEASUREMENTS
Medication use was ascertained through a baseline inventory. Physical performance measures (timed 6-meter walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up years 1, 3 and 6. Multivariable adjusted linear repeated- measures models adjusted for demographic and health characteristics.
RESULTS
ACE inhibitor use was negatively associated with mean grip strength at baseline (22.40 kg, 95% confidence interval [CI] 21.89, 22.91 versus 23.18 kg, 95% CI 23.02, 23.34; P = .005) and a greater mean annual change in number of chair stands (−.182, 95% CI −.217, −.147 versus −.145, 95% CI −.156, −.133; P = .05) compared to non-use. Statin use was not significantly associated with baseline or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands (P = .006) in the oldest women.
CONCLUSION
These results do not support an association of statin or ACE inhibitor use with slower decline in physical performance or muscle strength, and thus do not support the use of these medications for preserving functional status in older adults.
doi:10.1111/jgs.12029
PMCID: PMC3521070  PMID: 23176078
ACE inhibitors; statins; physical performance; grip strength
21.  Education-related differences in physical performance after age 60: a cross-sectional study assessing variation by age, gender and occupation 
BMC Public Health  2013;13:641.
Background
Having a low level of education has been associated with worse physical performance. However, it is unclear whether this association varies by age, gender or the occupational categories of manual and non-manual work. This study examined whether there are education-related differences across four dimensions of physical performance by age, gender or occupational class and to what extent chronic diseases and lifestyle-related factors may explain such differences.
Methods
Participants were a random sample of 3212 people, 60 years and older, both living in their own homes and in institutions, from the Swedish National Study on Aging and Care, in Kungsholmen, Stockholm. Trained nurses assessed physical performance in grip strength, walking speed, balance and chair stands, and gathered data on education, occupation and lifestyle-related factors, such as physical exercise, body mass index, smoking and alcohol consumption. Diagnoses of chronic diseases were made by the examining physician.
Results
Censored normal regression analyses showed that persons with university education had better grip strength, balance, chair stand time and walking speed than people with elementary school education. The differences in balance and walking speed remained statistically significant (p < 0.05) after adjustment for chronic diseases and lifestyle. However, age-stratified analyses revealed that the differences were no longer statistically significant in advanced age (80+ years). Gender-stratified analyses revealed that women with university education had significantly better grip strength, balance and walking speed compared to women with elementary school education and men with university education had significantly better chair stands and walking speed compared to men with elementary school education in multivariate adjusted models. Further analyses stratified by gender and occupational class suggested that the education-related difference in grip strength was only evident among female manual workers, while the difference in balance and walking speed was only evident among female and male non-manual workers, respectively.
Conclusions
Higher education was associated with better lower extremity performance in people aged 60 to 80, but not in advanced age (80+ years). Our results indicate that higher education is associated with better grip strength among female manual workers and with better balance and walking speed among female and male non-manual workers, respectively.
doi:10.1186/1471-2458-13-641
PMCID: PMC3733740  PMID: 23842209
Educational status; Aging; Chronic diseases; Muscle strength; Walking; Postural balance
22.  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
23.  Smoking History and Physical Performance in Midlife: Results From the British 1946 Birth Cohort 
Background.
The adverse effects of smoking on individual medical conditions are well known; however, the cumulative effect of smoking on physical performance is not well characterized, particularly in midlife.
Methods.
In the British 1946 Birth Cohort Study, cigarette pack-years were examined with standing balance, chair rising, grip strength, and an overall composite index. Pack-years were calculated from data collected at ages 20, 25, 31, 36, 43, and 53 years, whereas physical performance, cognitive function, anthropometry, and spirometry were assessed at age 53 years in 2,394 men and women. Regression and cubic splines were used to assess the relationship between pack-years and physical performance.
Results.
Greater pack-years smoked were associated with lower overall physical performance and lower performance in standing balance and chair rising; however, there was no association with grip strength. For every 10 pack-years smoked, the overall physical performance index decreased by 0.11 SD (95% confidence interval: 0.07–0.15, p < .001), standing balance time decreased by 0.09 SD (0.05–0.13), and the reciprocal of chair rise time decreased by 0.11 SD (0.07–0.16). Adjustment for education, social class, lung function, cognitive function, and medical conditions attenuated the effect, but pack-years remained significantly associated with standing balance and chair rising time.
Conclusions.
Lifetime cigarette pack-years are strongly related to physical performance in the fifth decade of life, suggesting that smokers will enter older adulthood with decreased physiological reserve. As smoking prevalence remains high in many developed countries and is rapidly growing in developing countries, these findings underscore the need for effective smoking cessation and prevention programs.
doi:10.1093/gerona/glq199
PMCID: PMC3011956  PMID: 21071620
Physical performance; Aging; Smoking; Cigarette pack-years
24.  Chronic Inflammation Is Associated With Low Physical Function in Older Adults Across Multiple Comorbidities 
Background
Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status.
Methods
We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and anthropometric measures.
Results
Higher levels of CRP and IL-6, but not TNF-α, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results.
Conclusions
Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.
doi:10.1093/gerona/gln038
PMCID: PMC2657165  PMID: 19196644
Inflammation; Physical function; Aging; Comorbidities
25.  Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community 
Background
Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people.
Aim
To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older.
Methods
Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4‐metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non‐manual work.
Results
Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non‐manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non‐manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non‐manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non‐manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2).
Conclusions
A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.
doi:10.1136/oem.2005.023549
PMCID: PMC2092516  PMID: 16782827
lifetime occupation; physical performance; aging;  ilSIRENTE study

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