Work participation and risk factors for health-related job loss among older workers in the Health and Employment after Fifty (HEAF) study: Evidence from a 2-year follow-up period.

INTRODUCTION: Rapidly increasing population old age dependency ratios create a growing economic imperative for people to work to older ages. However, rates of older worker employment are only increasing slowly. Amongst a cohort of contemporary older workers, we investigated risk factors for health-related job loss (HRJL) over 2 years of follow-up. METHODS: HEAF is a population based cohort study of adults in England (aged 50-64 years at baseline) who provided information about socio-demographic characteristics, lifestyle, and work at baseline and annual follow-ups. Exits from paid work were mapped and risk factors for HRJL explored in a multiple-record survival dataset by Cox proportional hazards models. RESULTS: 2475 (75%) men and 2668 (66%) women were employed; 115 (4.6%) men and 182 (6.8%) women reported HRJL. Employment as road transport drivers/in vehicle trades (men), or as teaching/education/nursing/midwifery professionals or in caring personal services (women), was more frequent among people exiting work for health-related versus non-health-related reasons. Principal socio-demographic and lifestyle risk factors for HRJL were: struggling financially (men and women); low physical activity (men); being overweight or obese, and current smoking (women). Mutually adjusted work-related risk factors for HRJL were job dissatisfaction, and not coping with the physical (hazard ratio [95% confidence interval]: men 5.34[3.40,8.39]; women 3.73[2.48,5.60]) or mental demands (women only, 2.02[1.38,2.96]) of work. CONCLUSIONS: Employment characteristics of contemporary older workers differ by sex. Job satisfaction and perceived ability to cope with the physical and mental demands of work are key determinants of HRJL which employers could potentially influence to enable work to older ages.

Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

Understanding poor health behaviours as predictors of different types of hospital admission in older people: findings from the Hertfordshire Cohort Study.

BACKGROUND: Rates of hospital admission are increasing, particularly among older people. Poor health behaviours cluster but their combined impact on risk of hospital admission among older people in the UK is unknown. METHODS: 2997 community-dwelling men and women (aged 59-73) participated in the Hertfordshire Cohort Study (HCS). We scored (from 0 to 4) number of poor health behaviours engaged in at baseline (1998-2004) out of: current smoking, high weekly alcohol, low customary physical activity and poor diet. We linked HCS with Hospital Episode Statistics and mortality data to 31/03/2010 and analysed associations between the score and risk of different types of hospital admission: any; elective; emergency; long stay (>7 days); 30-day readmission (any, or emergency). RESULTS: 32%, 40%, 20% and 7% of men engaged in 0, 1, 2 and 3/4 poor health behaviours; corresponding percentages for women 51%, 38%, 9%, 2%. 75% of men (69% women) experienced at least one hospital admission. Among men and women, increased number of poor health behaviours was strongly associated (p<0.01) with greater risk of long stay and emergency admissions, and 30-day emergency readmissions. Hazard ratios (HRs) for emergency admission for 3/4 poor health behaviours in comparison with none were: men, 1.37 (95% CI 1.11 to 1.69); women, 1.84 (95% CI 1.22 to 2.77). Associations were unaltered by adjustment for age, body mass index and comorbidity. CONCLUSIONS: Clustered poor health behaviours are associated with increased risk of hospital admission among older people in the UK. Lifecourse interventions to reduce number of poor health behaviours could have substantial beneficial impact on health and use of healthcare in later life.

Grip strength among community-dwelling older people predicts hospital admission during the following decade.

BACKGROUND: Lower grip strength on admission to hospital is known to be associated with longer stay, but the link between customary grip and risk of future admission is less clear. OBJECTIVE: To compare grip strength with subsequent risk of hospital admission among community-dwelling older people in a U.K. setting. DESIGN: Cohort study with linked administrative data. SETTING: Hertfordshire, U.K. SUBJECTS: A total of 2,997 community-dwelling men and women aged 59-73 years at baseline. METHODS: The Hertfordshire Cohort Study (HCS) participants completed a baseline assessment between 1998 and 2004, during which grip strength was measured. Hospital Episode Statistics and mortality data to March 2010 were linked with the HCS database. Statistical models were used to investigate the association of grip strength with subsequent elective, emergency and long-stay hospitalisation and readmission. RESULTS: There was a statistically significant negative association between grip strength and all classes of admission in women [unadjusted hazard ratio per standard deviation (SD) decrease in grip strength for: any admission/death 1.10 (95% CI: 1.06, 1.14), elective admission/death 1.09 (95% CI: 1.05, 1.13), emergency admission/death 1.21 (95% CI: 1.13, 1.31), long-stay admission/death 1.22 (95% CI: 1.13, 1.32) and unadjusted relative risk per SD decrease in grip strength for 30-day readmission/death 1.30 (95% CI: 1.19, 1.43)]. These associations remained significant after adjustment for potential confounding factors (age, height, weight for height, smoking, alcohol, social class). In men, unadjusted rates for emergency admission/death, long-stay admission/death and readmission/death were significantly associated with grip strength; associations that similarly withstood adjustment. CONCLUSION: This study provides the first evidence that grip strength among community-dwelling men and women in the U.K. is associated with risk of hospital admission over the following decade.

Processed meat consumption and lung function: modification by antioxidants and smoking.

Unhealthy dietary patterns are associated with poor lung function. It is not known whether this is due to low consumption of antioxidant-rich fruit and vegetables, or is a consequence of higher intakes of harmful dietary constituents, such as processed meat. We examined the individual and combined associations of processed meat, fruit and vegetable consumption and dietary total antioxidant capacity (TAC) with lung function among 1551 males and 1391 females in the UK in the Hertfordshire Cohort Study. Diet was assessed using a food frequency questionnaire. After controlling for confounders, processed meat consumption was negatively associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio in males and females, while fruit and vegetable consumption and dietary TAC were positively associated with FEV1 and FVC, but not FEV1/FVC ratio. In males, the negative association between processed meat consumption and FEV1 was more marked in those who had low fruit and vegetable consumption (p=0.035 for interaction), and low dietary TAC (p=0.025 for interaction). The deficit in FEV1/FVC associated with processed meat consumption was larger in males who smoked (p=0.022 for interaction). Higher processed meat consumption is associated with poorer lung function, especially in males who have lower fruit and vegetable consumption or dietary TAC, and among current smokers.

Clustering of lifestyle risk factors and poor physical function in older adults: the Hertfordshire cohort study.

OBJECTIVES: To examine the relationship between number of lifestyle risk factors (out of low physical activity, poor diet, obesity, smoking) and physical function in older community-dwelling men and women. DESIGN: Cross-sectional study, Hertfordshire, United Kingdom. PARTICIPANTS: Men (n = 1,682) and women (n = 1,540) aged 59 to 73. MEASUREMENTS: Physical activity was assessed using an administered questionnaire with a score from 0 to 100; low activity was defined as a score of 50 or less. Diet was assessed using a food frequency questionnaire; diet quality was assessed according to a score for a principal component analysis-defined "healthy" dietary pattern. Poor diet was categorized as a dietary pattern score in the lowest quarter of the distribution. Obesity was defined as a body mass index of 30.0 kg/m(2) or more. Physical function was assessed according to self-report (SF-36); poor function was defined as a score in lowest quarter of the distribution. A subgroup of participants had objective assessments of physical function (Timed Up-and-Go Test, timed 3-m walk, chair rises, one-legged standing balance). RESULTS: There was a graded increase in prevalence of poor self-reported physical function in men and women with increasing number of risk factors (men, adjusted odds ratio (AOR) for 3 or 4 risk factors vs none = 3.79, 95% confidence interval (CI) = 2.31-6.21; women, AOR = 5.37, 95% CI = 2.66-10.84). With the exception of balance, the objective assessments also showed graded relationships with number of risk factors, such that more risk factors was associated with poorer physical function. CONCLUSION: These modifiable lifestyle risk factors are linked to marked differences in risk of poorer physical function in older adults. Efforts to encourage healthy lifestyles have the potential to improve physical function and to promote healthier ageing.

Hertfordshire sarcopenia study: design and methods.

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.

A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study.

OBJECTIVE: We sought evidence of association of candidate single nucleotide polymorphisms (SNP) within the growth hormone-insulin-like growth factor 1 (IGF1) axis, largely selected on the basis of functional data available at the time of our study, with adult bone mass. METHODS: Four hundred ninety-eight men and 468 women aged 59-71 years were recruited. A lifestyle questionnaire was administered, and bone mineral content (BMC) and bone mineral density (BMD) were measured at the lumbar spine and femoral neck. Two hundred fifty-four men and 271 women had repeat bone densitometry 4 years later. DNA was obtained from whole blood samples using standard extraction techniques. Single nucleotide variants in the growth hormone releasing hormone gene (GHRH, G/A 223 Phe75Leu, rs4988492), growth hormone releasing hormone receptor gene (GHRHR, G/A 217, Ala57Thr, rs4988496), the growth hormone secretagogue receptor gene (GHSR, T/C, Gly57Gly, rs495225), and the growth hormone receptor gene (GHR, T/G, noncoding, rs2940944) were analyzed. RESULTS: In both sexes, allelic variation in the gene encoding GHRH was associated with BMC and BMD at the proximal femur and lumbar spine, with results generally stronger in women. In women, the mean BMC lumbar spine within the GHRH 11 genotype was 56.9 g, while that of the GHRH 12 genotype was 68.4 g [p < 0.001, fully adjusted for age, body mass index, cigarette and alcohol consumption, dietary calcium intake, physical activity, years since menopause, and hormone replacement therapy (HRT) use]; corresponding figures for BMD lumbar spine (GHRH 11 genotype) were 0.96 g/cm(2) versus 1.10 g/cm(2) (p < 0.001 fully adjusted). CONCLUSION: We have demonstrated a relationship between allelic variation in the gene encoding GHRH and bone density; we welcome attempts at replication in other populations.

Interaction between birthweight and polymorphism in the calcium-sensing receptor gene in determination of adult bone mass: the Hertfordshire cohort study.

OBJECTIVE: We sought evidence of interaction between single-nucleotide polymorphisms (SNP) in the calcium-sensing receptor (CASR) gene and early life in determination of bone mineral density (BMD) among individuals from the Hertfordshire Cohort Study. METHODS: Four hundred ninety-eight men and 468 women aged 59-71 years were recruited. A lifestyle questionnaire was administered and BMD at lumbar spine and femoral neck was measured. DNA was obtained from whole blood samples using standard extraction techniques. Five SNP of the CASR gene termed CASRV1 (rs1801725, G-->T, S986A), CASRV2 (rs7614486, T-->G, untranslated), CASRV3 (rs4300957, untranslated), CASRV4 (rs3804592 G-->A, intron), and CASRV5 (rs1393189, T-->C, intron) were analyzed. RESULTS: Among women the 11 genotype of the CASRV3 SNP was associated with higher lumbar spine BMD within the lowest birthweight tertile, while the opposite pattern was observed among individuals in the highest birthweight tertile (test for interaction on 1 df, p = 0.005, adjusted for age, body mass index, physical activity, dietary calcium intake, cigarette and alcohol consumption, social class, menopausal status, and hormone replacement therapy use). Similar relationships were seen at the total femur (p = 0.042, fully adjusted) with birthweight and at the total femur according to weight at 1 year tertile among women (p < 0.001, fully adjusted). One haplotype was associated with lumbar spine BMD in women (p = 0.008, fully adjusted); these findings were replicated in a second cohort. CONCLUSION: We have found evidence of an interaction between a SNP of the CASR gene and birthweight in determination of bone mass in a UK female population.

Specific associations of insulin resistance with impaired health-related quality of life in the Hertfordshire Cohort Study.

Insulin resistance is a metabolic abnormality that underlies Type 2 diabetes, the metabolic syndrome and cardiovascular disease, but it may also be associated with more global health deficits. This study assessed associations of insulin resistance with health-related quality of life (HRQoL) in different domains of physical and mental health in a large elderly population study. Cross-sectional data of 1212 participants from the Hertfordshire Cohort Study were analysed. Insulin resistance was assessed by the homeostatic model assessment (HOMA-IR), and HRQoL was measured using the SF-36 health survey. Poor HRQoL was defined by a score lower than the sex-specific 10th percentile of each scale, and logistic regressions yielded odds ratios in relation to the HOMA-IR scores. Subsequent analyses adjusted for the influence of age, smoking, alcohol consumption, social class, BMI, coronary heart disease and depression. Results showed an increase in poor HRQoL with an increase in HOMA-IR scores for physical functioning (OR = 2.29; CI: 1.67-3.13), vitality (OR = 1.45; CI: 1.05-2.00), and general health (OR = 1.62; CI: 1.19-2.21). In men, but not in women, associations with physical functioning were independent of confounding variables. The results indicate that insulin resistance is associated with poor HRQoL in domains of physical health, but not in domains of mental health.

A study of TH01 and IGF2-INS-TH haplotypes in relation to smoking initiation in three independent surveys.

OBJECTIVES: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. METHODS: A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. RESULTS: Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. CONCLUSION: This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.

Circulating cortisone levels are associated with biochemical markers of bone formation and lumbar spine BMD: the Hertfordshire Cohort Study.

OBJECTIVE: Cortisone is an endogenous corticosteroid that has negligible intrinsic glucocorticoid activity but can be converted to the active corticosteroid cortisol by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 is expressed in osteoblasts and may play a role in determining susceptibility to glucocorticoid-induced osteoporosis. In intact osteoblasts enzyme activity, and thus cortisol generation, is dependent on substrate concentration with an almost linear increase in activity across the physiological range. We have therefore attempted to measure the impact of 11beta-HSD1 activity on bone in vivo by examining the association of circulating cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort of women and men. DESIGN AND SUBJECTS: Baseline cross-sectional association study involving 135 women and 171 men aged 61-73 years from the Hertfordshire Cohort Study and a 4 year follow-up study examining changes in BMD. MEASUREMENTS: Serum cortisone, cortisol and osteocalcin, and urinary type I collagen cross-linked N-telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at baseline and 4 years later. RESULTS: In men serum cortisone levels were negatively correlated with serum osteocalcin (r = -0.20, P = 0.01); a similar relationship was seen in women (r = -0.16, P = 0.06). No correlation was seen between serum cortisone and urinary NTX (r = 0.03, P = 0.74 for women; r = -0.03, P = 0.72 for men). A negative correlation was observed between serum cortisone and spine BMD in women (r = -0.18, P = 0.04); a similar relationship was also seen in men (r =-0.14, P = 0.07). However, cortisone did not correlate with BMD at the femoral neck or total hip or changes in BMD at any site over time. In analyses adjusted for adiposity, osteoarthritis grade and a range of life-style variables, these relationships did not change substantially. All these relationships were independent of cortisol concentrations. CONCLUSIONS: The most plausible explanation for the association of circulating cortisone levels with osteocalcin is the presence of 11beta-HSD1 activity within osteoblasts. The measurement of serum cortisone may independently give insights into the action of glucocorticoids on bone.

Does sarcopenia originate in early life? Findings from the Hertfordshire cohort study.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia. METHODS: We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size. RESULTS: Grip strength was most strongly associated with birth weight in men (r = 0.19, p < .001) and women (r = 0.16, p < .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results. CONCLUSIONS: Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.