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1.  Coding Geriatric syndromes: How good are we? 
High quality coding of hospital activity is important because the data is used for resource allocation and measuring performance. There is little information on the quality of coding of admissions of frail older people who have multiple diagnoses, co-morbidities and functional impairment. Presence or absence of four geriatric syndromes and eight medical conditions was noted on case note review (CNR). Discharge summaries (DS) and hospital coding (HC) were reviewed and compared with the CNR. Forty patients had at least one geriatric syndrome noted in the DS; 16 (40.0%) were captured by the HC. Of 57 patients with at least one medical condition noted in the DS, 52 (91.2%) were captured by the HC (p<0.0001 for difference in HC capture rates). We have demonstrated poor capture of information on geriatric syndromes compared to medical conditions in discharge summaries and hospital coding and propose a problem list bookmark approach to improve this.
PMCID: PMC3191527  PMID: 22003315
Coding; routine data; geriatric syndromes; frailty
3.  The developmental origins of sarcopenia: using peripheral quantitative computed tomography to assess muscle size in older people 
Background
A number of studies have shown strong graded positive relationships between size at birth and grip strength and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size.
Methods
We studied 313 men and 318 women born in Hertfordshire UK between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size.
Results
Birth weight was positively related to forearm muscle area in the men (r = 0.24 p < 0.0001) and women (r = 0.17 p =0.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r=0.13, p=0.03) and in the women (r=0.17, p=0.004). These relationships were all attenuated by adjustment for adult size.
Conclusion
We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the aetiology of sarcopenia and to developing effective interventions.
PMCID: PMC2652118  PMID: 18772471
4.  Falls, sarcopenia and growth in early life 
American journal of epidemiology  2006;164(7):665-671.
Recent studies have shown that people with poor early growth have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls but it is not known whether poor early growth is related to falls. We investigated this in the Hertfordshire Cohort Study where 2148 participants completed a falls history. Grip strength was used as a marker of sarcopenia. Birth weight, weight at one year and conditional infant growth were analysed in relation to falls history. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height and walking speed in men and women as well as to lower conditional infant growth in men (OR 1.27 [95% CI 1.04, 1.56] per SD decrease in conditional infant growth, p=0.02). This association was attenuated after adjustment for grip strength. Our findings support an association between poor early growth and falls in older men which appears to be mediated partly through sarcopenia. The lack of relationship with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important for risk of falls in later life.
doi:10.1093/aje/kwj255
PMCID: PMC2062502  PMID: 16905644
Falls accidental; muscle skeletal; muscle development; frail older adults; geriatrics; epidemiology; cohort studies
5.  Prevalence and correlates of frailty among community-dwelling older men and women: findings from the Hertfordshire Cohort Study 
Age and ageing  2009;39(2):197-203.
Background
frailty, a multi-dimensional geriatric syndrome, confers a high risk for falls, disability, hospitalisation and mortality. The prevalence and correlates of frailty in the UK are unknown.
Methods
frailty, defined by Fried, was examined among community-dwelling young-old (64-74 years) men (n = 320) and women (n = 318) who participated in the Hertfordshire Cohort Study, UK.
Results
the prevalence of frailty was 8.5% among women and 4.1% among men (P = 0.02). Among men, older age (P = 0.009), younger age of leaving education (P = 0.05), not owning/mortgaging one’s home (odds ratio [OR] for frailty 3.45 [95% confidence interval {CI} 1.01-11.81], P = 0.05, in comparison with owner/mortgage occupiers) and reduced car availability (OR for frailty 3.57 per unit decrease in number of cars available [95% CI 1.32, 10.0], P = 0.01) were associated with increased odds of frailty. Among women, not owning/mortgaging one’s home (P = 0.02) was associated with frailty. With the exception of car availability among men (P = 0.03), all associations were non-significant (P > 0.05) after adjustment for co-morbidity.
Conclusions
frailty is not uncommon even among community-dwelling young-old men and women in the UK. There are social inequalities in frailty which appear to be mediated by co-morbidity.
doi:10.1093/ageing/afp204
PMCID: PMC3546311  PMID: 20007127
frailty; prevalence; older people; social inequalities; co-morbidity; elderly
6.  New horizons in the pathogenesis, diagnosis and management of sarcopenia 
Age and Ageing  2013;42(2):145-150.
Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. One of the most important recent developments has been convergence in the operational definition of sarcopenia combining measures of muscle mass and strength or physical performance. This has been accompanied by considerable progress in understanding of pathogenesis from animal models of sarcopenia. Well-described risk factors include age, gender and levels of physical activity and this knowledge is now being translated into effective management strategies including resistance exercise with recent interest in the additional role of nutritional intervention. Sarcopenia is currently a major focus for drug discovery and development although there remains debate about the best primary outcome measure for trials, and various promising avenues to date have proved unsatisfactory. The concept of ‘new tricks for old drugs’ is, however, promising, for example, there is some evidence that the angiotensin-converting enzyme inhibitors may improve physical performance. Future directions will include a deeper understanding of the molecular and cellular mechanisms of sarcopenia and the application of a lifecourse approach to understanding aetiology as well as to informing the optimal timing of interventions.
doi:10.1093/ageing/afs191
PMCID: PMC3575121  PMID: 23315797
sarcopenia; skeletal muscle; ageing; pathogenesis; diagnosis; exercise; nutrition; drug treatment; life course; epidemiology; older people
7.  Southampton mealtime assistance study: design and methods 
BMC Geriatrics  2013;13:5.
Background
Malnutrition is common in older people in hospital and is associated with adverse clinical outcomes including increased mortality, morbidity and length of stay. This has raised concerns about the nutrition and diet of hospital in-patients. A number of factors may contribute to low dietary intakes in hospital, including acute illness and cognitive impairment among in-patients. The extent to which other factors influence intake such as a lack of help at mealtimes, for patients who require assistance with eating, is uncertain. This study aims to evaluate the effectiveness of using trained volunteer mealtime assistants to help patients on an acute medical ward for older people at mealtimes.
Methods/design
The study design is quasi-experimental with a before (year one) and after (year two) comparison of patients on the intervention ward and parallel comparison with patients on a control ward in the same department. The intervention in the second year was the provision of trained volunteer mealtime assistance to patients in the intervention ward. There were three components of data collection that were repeated in both years on both wards. The first (primary) outcome was patients’ dietary intake, collected as individual patient records and as ward-level balance data over 24 hour periods. The second was clinical outcome data assessed on admission and discharge from both wards, and 6 and 12 months after discharge. Finally qualitative data on the views and experience of patients, carers, staff and volunteers was collected through interviews and focus groups in both years to allow a mixed-method evaluation of the intervention.
Discussion
The study will describe the effect of provision of trained volunteer mealtime assistants on the dietary intake of older medical in-patients. The association between dietary intake and clinical outcomes including malnutrition risk, body composition, grip strength, length of hospital stay and mortality will also be determined. An important component of the study is the use of qualitative approaches to determine the views of patients, relatives, staff and volunteers on nutrition in hospital and the impact of mealtime assistance.
Trial registration
Trial registered with ClinicalTrials.gov NCTO1647204
doi:10.1186/1471-2318-13-5
PMCID: PMC3547699  PMID: 23294981
Nutrition; Older; Volunteer; Mealtime assistance; Dietary intake; Hospital
8.  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
9.  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
10.  ACTN3 genotype, athletic status and lifecourse physical capability: meta-analysis of the published literature and findings from nine studies 
Human mutation  2011;10.1002/humu.21526.
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
11.  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
12.  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
13.  How useful are the SF-36 sub-scales in older people? Mokken scaling of data from the HALCyon programme 
Quality of Life Research  2011;20(7):1005-1010.
Purpose
To evaluate two psychometric properties of SF-36, namely unidimensionality and reliability.
Methods
The data are from three cohorts in the HALCyon collaborative research programme into healthy ageing: Aberdeen Birth Cohort 1936 (n = 428), Hertfordshire Ageing Study (n = 358) and Hertfordshire Cohort Study (n = 3,216). The Mokken scaling model was applied to each sub-scale of SF-36 to evaluate unidimensionality as indicated by scalability. The lower bound for internal consistency reliability was determined by Cronbach’s alpha.
Results
All six sub-scales of SF-36, with the exception of general health (GH) and mental health (MH), demonstrated strong scalability (0.5 ≤ H < 1). The results were consistent across all 3 cohorts. Both GH and MH showed medium scalability (0.4 ≤ H <0.55), although individual items ‘sick easier..’, ‘as healthy as..’ and ‘expect to get worse’ of the GH sub-scale and ‘nervous’, ‘happy’ in the MH sub-scale had low scalability (H < 0.4) in the oldest cohort (aged 73–83). Cronbach’s alphas for all sub-scales were between 0.70 and 0.92.
Conclusions
The unidimensionality and reliability of the sub-scales of SF-36 are sufficient to make this a useful measure of health-related quality of life in older people. Caution is needed when interpreting the results for GH and MH in the oldest cohort due to the poor unidimensionality.
doi:10.1007/s11136-010-9838-7
PMCID: PMC3161183  PMID: 21225350
SF-36; Psychometric properties; Unidimensionality; Reliability; Cronbach’s alpha; Mokken scaling
14.  Hertfordshire sarcopenia study: design and methods 
BMC Geriatrics  2010;10:43.
Background
Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms.
Methods
One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study.
Discussion
The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.
doi:10.1186/1471-2318-10-43
PMCID: PMC2909243  PMID: 20587018
15.  The SF-36: a simple, effective measure of mobility-disability for epidemiological studies 
Background
Mobility disability is a major problem in older people. Numerous scales exist for the measurement of disability but often these do not permit comparisons between study groups. The physical functioning (PF) domain of the established and widely used Short Form-36 (SF-36) questionnaire asks about limitations on ten mobility activities.
Objectives
To describe prevalence of mobility disability in an elderly population, investigate the validity of the SF-36 PF score as a measure of mobility disability, and to establish age and sex specific norms for the PF score.
Methods
We explored relationships between the SF-36 PF score and objectively measured physical performance variables among 349 men and 280 women, 59-72 years of age, who participated in the Hertfordshire Cohort Study (HCS). Normative data were derived from the Health Survey for England (HSE) 1996.
Results
32% of men and 46% of women had at least some limitation in PF scale items. Poor SF-36 PF scores (lowest fifth of the gender-specific distribution) were related to: lower grip strength; longer timed-up-and-go, 3m walk, and chair rises test times in men and women; and lower quadriceps peak torque in women but not men. HSE normative data showed that median PF scores declined with increasing age in men and women.
Conclusion
Our results are consistent with the SF-36 PF score being a valid measure of mobility disability in epidemiological studies. This approach might be a first step towards enabling simple comparisons of prevalence of mobility disability between different studies of older people. The SF-36 PF score could usefully complement existing detailed schemes for classification of disability and it now requires validation against them.
PMCID: PMC2654814  PMID: 19151909
epidemiology; physical functioning; disability; ageing; mobility
16.  Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire Cohort Study 
OBJECTIVES
To examine relationships between diet and grip strength in older men and women, and to determine whether these relationships are modified by prenatal growth.
DESIGN
Cross-sectional and retrospective cohort study
SETTING
Hertfordshire, UK
PARTICIPANTS
Two thousand, nine hundred and eighty three men and women aged 59 to 73 years who were born and still live in Hertfordshire, UK
MEASUREMENTS
Weight at birth recorded in Health Visitor ledgers. Current food and nutrient intake assessed using an administered food frequency questionnaire, grip strength was measured with a hand-held dynamometer.
RESULTS
Grip strength was positively associated with height and weight at birth, and inversely related to age (all P<0.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43kg (95% CI 0.13 to 0.74) in men (P=0.005), and 0.48kg (95% CI 0.24 to 0.72) in women (P<0.001), was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength.
CONCLUSION
These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the anti-inflammatory actions of n-3 fatty acids may play a role in the prevention of sarcopenia.
doi:10.1111/j.1532-5415.2007.01478.x
PMCID: PMC2493054  PMID: 18005355
diet; sarcopenia; grip strength
17.  Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study 
Background
Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data are available relating bone density, lipid profile and anthropometric measures. We addressed these relationships in a large well-characterised cohort of men and women (The Hertfordshire Cohort Study, UK).
Methods
Four hundred and sixty five men and 448 women from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur.
Results
BMD at the lumbar spine (males r=0.15, p=0.001; females r=0.14 p=0.003) and total femoral region (males r=0.18, p=0.0001; females r==0.16, p=0.0008) was related to serum triglyceride level, even after adjustment for waist hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r=−0.15, p=0.001) and total femoral BMD (males r=−0.15, p=0.002; females r=−0.23, p<0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist hip ratio. No relationships were seen between total or LDL cholesterol with BMD.
Conclusions
We have demonstrated relationships between lipid profile and BMD that are robust to adjustment for one measure of central obesity (waist-hip ratio) but not total body fat.
doi:10.1093/qjmed/hcm023
PMCID: PMC2080690  PMID: 17449479
lipid; bone; cohort; anthropometry; obesity
18.  Growth in early life predicts bone strength in late adulthood 
Bone  2007;41(3):400-405.
Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.
We studied 313 men and 318 women born in Hertfordshire between 1931-39 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500).
Birthweight and conditional weight at one year were strongly related to radial and tibial length in both sexes (p<0.001), and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use and menopausal status in women. Among men, BMI was strongly positively associated with radial (r=0.46, p=0.001) and tibial (r=0.24, p=0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p=0.0002; tibia: p=0.08) and trabecular BMD (radius: p=0.08; tibia: p=0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p=0.0002; tibia: p=0.001) and trabecular (radius: p=0.008; tibia: p=0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p=0.006; fracture load x: p=0.005; fracture load y: p=0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p=0.0001), cortical (p<0.005) and trabecular (p=0.0002) BMD, poorer forearm bone strength [polar SSI (p=0.006), fracture load X & Y (p=0.02)], and lower tibial total (p<0.001), cortical (p=0.008) and trabecular (p=0.0001) BMD.
We have shown that growth in early life is associated with bone size and strength in a UK population aged 65-73 years. Lifestyle factors were associated with volumetric bone density in this population.
doi:10.1016/j.bone.2007.05.007
PMCID: PMC2080691  PMID: 17599849
Bone; Strength; Density; Programming; Epidemiology
19.  Growth in early life predicts bone strength in late adulthood: The Hertfordshire Cohort Study 
Bone  2007;41(3):400-405.
Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.
We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500).
Birthweight and conditional weight at 1 year were strongly related to radial and tibial length in both sexes (p < 0.001) and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use, and menopausal status in women. Among men, BMI was strongly positively associated with radial (r = 0.46, p = 0.001) and tibial (r = 0.24, p = 0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p = 0.0002; tibia: p = 0.08) and trabecular BMD (radius: p = 0.08; tibia: p = 0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p = 0.0002; tibia: p = 0.001) and trabecular (radius: p = 0.008; tibia: p = 0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p = 0.006; fracture load X: p = 0.005; fracture load Y: p = 0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p = 0.0001), cortical (p < 0.005) and trabecular (p = 0.0002) BMD, poorer forearm bone strength [polar SSI (p = 0.006), fracture load X and Y (p = 0.02)], and lower tibial total (p < 0.001), cortical (p = 0.008), and trabecular (p = 0.0001) BMD.
We have shown that growth in early life is associated with bone size and strength in a UK population aged 65–73 years. Lifestyle factors were associated with volumetric bone density in this population.
doi:10.1016/j.bone.2007.05.007
PMCID: PMC2080691  PMID: 17599849
Bone; Strength; Density; Programming; Epidemiology
20.  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
21.  A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme 
PLoS ONE  2012;7(1):e29883.
Background
Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four 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 evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.
Conclusion
Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
doi:10.1371/journal.pone.0029883
PMCID: PMC3254646  PMID: 22253814
22.  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
23.  Randomized controlled trial of the efficacy of aerobic exercise in reducing metabolic risk in healthy older people: The Hertfordshire Physical Activity Trial 
Background
While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group.
Methods/Design
We aim to recruit 100 participants born between 1931–1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing.
Discussion
Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group.
Trial Registration
Current Controlled Trials: ISRCTN60986572
doi:10.1186/1472-6823-9-15
PMCID: PMC2708167  PMID: 19545359

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