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, 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, United Kingdom 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 &lt; .0001) and women (r = 0.17, p = .003). There were similar but weaker associations between birth weight and calf muscle area in the men (r = 0.13, p = .03) and in the women (r = 0.17, p = .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 etiology of sarcopenia and to developing effective interventions<br/

Morbidities Among Older Workers And Work Exit : The Heaf Cohort

Funding: The HEAF study is funded by grant awards from Versus Arthritis (formerly Arthritis Research UK) (19817 and 20665) and the Medical Research Council programme grant (MC_UU_12011/5); and the Economic and Social Research Council and Medical Research Council jointly (ES/L002663/1); the study is coordinated by the MRC Lifecourse Epidemiology Unit, Southampton. GN and CHL receive financial support from the MRC Versus Arthritis Centre for Musculoskeletal Health and Work. Acknowledgements: We wish to thank Professor Keith Palmer for his work incepting the HEAF cohort and Dr Stephen Duffield for his contribution to the coding of the CPRD data. Also, we are grateful to the Clinical Practice Research Datalink and the 24 general practices that supported data collection, the staff of the MRC Lifecourse Epidemiology Unit who provided data entry and computing support (notably Vanessa Cox). Finally, we thank the HEAF participants for giving their time so generously to participate in the study.Peer reviewedPostprin

Global variation in grip strength: a systematic review and meta-analysis of normative data.

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut 209 Global variation in grip strength points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard. Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region. Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of −0.85 SDs (95% CI: −0.94, −0.76). Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing region

Frailty, prefrailty and employment outcomes in Health and Employment After Fifty (HEAF) Study

Objectives Demographic changes are requiring people to work longer. No previous studies, however, have focused on whether the ‘frailty’ phenotype (which predicts adverse events in the elderly) is associated with employment difficulties. To provide information, we assessed associations in the Health and Employment After Fifty Study, a population-based cohort of 50–65-year olds.Methods Subjects, who were recruited from 24 English general practices, completed a baseline questionnaire on ‘prefrailty’ and ‘frailty’ (adapted Fried criteria) and several work outcomes, including health-related job loss (HRJL), prolonged sickness absence (&gt;20 days vs less, past 12 months), having to cut down substantially at work and difficulty coping with work's demands. Associations were assessed using logistic regression and population attributable fractions (PAFs) were calculated.Results In all, 3.9% of 8095 respondents were classed as ‘frail’ and 31.6% as ‘prefrail’. Three-quarters of the former were not in work, while 60% had left their last job on health grounds (OR for HRJL vs non-frail subjects, 30.0 (95% CI 23.0 to 39.2)). Among those in work, ORs for prolonged sickness absence, cutting down substantially at work and struggling with work's physical demands ranged from 10.7 to 17.2. The PAF for HRJL when any frailty marker was present was 51.8% and that for prolonged sickness absence was 32.5%. Associations were strongest with slow reported walking speed. Several associations were stronger in manual workers than in managers.Conclusions Fried frailty symptoms are not uncommon in mid-life and are strongly linked with economically important adverse employment outcomes. Frailty could represent an important target for prevention.</p

Influences on diet quality in older age:The importance of social factors

Background: poor diet quality is common among older people, but little is known about influences on food choice, including the role of psychosocial factors at this age.Objective: to identify psychosocial correlates of diet quality in a community-dwelling population of men and women aged 59–73 years; to describe relationships with change in diet quality over 10 years.Design: Longitudinal cohort, Hertfordshire Cohort Study (HCS).Subjects: HCS participants assessed at baseline (1998–2003: 1,048 men, 862 women); 183 men and 189 women re-assessed in 2011.Methods: diet was assessed by administered food frequency questionnaire; diet scores were calculated to describe diet quality at baseline and follow-up. A range of psychosocial factors (social support, social network, participation in leisure activities, depression and anxiety, sense of control) were assessed by questionnaire.Results: at baseline, better diet quality was related to a range of social factors, including increased confiding/emotional social support (men and women), practical support (men) and a larger social network (women) (all P &lt; 0.05). For both men and women, greater participation in social and cognitive leisure activities was related to better diet quality (P &lt; 0.005). There were few associations between measured psychosocial factors at baseline and change in diet score over 10 years, in the follow-up sub-group. However, greater participation in leisure activities, especially cognitive activities, at baseline was associated with smaller declines in diet quality over the 10-year follow-up period for both men (P = 0.017) and women (P = 0.014).Conclusions: in community-dwelling older adults, a range of social factors, that includes greater participation in leisure activities, were associated with diets of better quality

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; 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.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; 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.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt

Body mass index, muscle strength and physical performance in older adults from eight cohort studies: the HALCyon programme.

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

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Smoking does not accelerate leucocyte telomere attrition:A meta-analysis of 18 longitudinal cohorts

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr−1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr−1. Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks