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Key summary points: Aim: To propose a set of principles that can be used to select long-term conditions when studying multimorbidity in hospitalised patients and apply these principles to identify a list of conditions. Findings: We have outlined a list of principles and applied these to identify a list of 60 long-term conditions that can be utilised when conducting research on multimorbidity in hospitalised patients in the UK and other countries with similar population health profiles. We have mapped this list of 60 conditions to the International Classification of Diseases 10th revision (ICD-10) codes, drawing on clinical and coding expertise, to facilitate consistency in the operationalisation of this list. Message: Our work addresses the need for greater transparency and consistency in the approach to the definition of multimorbidity and provides clear recommendations for those conducting research on multimorbidity in the hospital context. Purpose: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of multimorbidity in hospitals; (2) apply these principles and identify a list of long-term conditions; (3) operationalise this list by mapping it to International Classification of Diseases 10th revision (ICD-10) codes. Methods: Review by independent assessors and ratification by an interdisciplinary programme management group. Results: Agreement was reached that when defining multimorbidity in hospitals for research purposes all conditions must meet the following four criteria: (1) medical diagnosis; (2) typically present for ≥ 12 months; (3) at least one of currently active; permanent in effect; requiring current treatment, care or therapy; requiring surveillance; remitting-relapsing and requiring ongoing treatment or care, and; (4) lead to at least one of: significantly increased risk of death; significantly reduced quality of life; frailty or physical disability; significantly worsened mental health; significantly increased treatment burden (indicated by an increased risk of hospital admission or increased length of hospital stay). Application of these principles to two existing lists of conditions led to the selection of 60 conditions that can be used when defining multimorbidity for research focused on hospitalised patients. ICD-10 codes were identified for each of these conditions to ensure consistency in their operationalisation. Conclusions: This work contributes to achieving the goal of greater transparency and consistency in the approach to the study of multimorbidity, with a specific focus on the UK hospital setting. [ABSTRACT FROM AUTHOR]

Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47–84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = − 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = − 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the impact of applying different SARC-F cut-points for the identification of muscle weakness in an older clinical population. Methods: We included 159 men and 311 women aged 56–98 years who had completed the SARC-F questionnaire and had their maximum grip strength measured at an Older People's Medicine Day Unit. We applied cut-points of ≥ 4, 3 and 2 to SARC-F and tested agreement with muscle weakness (grip strength < 27kg men, < 16kg women) in analyses stratified by sex and obesity status. Results: Prevalence of muscle weakness was 86.8% and 82.6% in men and women, respectively. Sensitivity of the SARC-F increased at lower cut-points (e.g. 81% for ≥ 4 vs 97% for ≥ 2 in women). There was typically greater sensitivity among women than men and among those classified as obese vs non-obese. Conclusions: These findings suggest that different cut-points may be required to optimise the utility of SARC-F for identifying muscle weakness in different patient sub-groups. [ABSTRACT FROM AUTHOR]

Background: The prevalence of sarcopenia (reduced skeletal muscle strength and mass), Parkinson's disease (PD) and Parkinson's related disorders (PRD) all increase with age. They also share risk factors and pathogenetic features. An increased prevalence of sarcopenia in PD and PRD than the general population was thus postulated. Methods: Four databases were searched using predefined literature search strategies. Studies conducted in participants with PD or PRD reporting the prevalence of sarcopenia and those providing data to compute the prevalence were included. Pre-sarcopenia, probable/possible sarcopenia and confirmed sarcopenia were defined according to the main sarcopenia working groups. Risk of bias was assessed using the AXIS tool. Results: 1978 studies were identified; 97 assessed in full; 14 met inclusion criteria. The median study quality score was 15/20. The range of probable sarcopenia was 23.9 to 66.7%, and it did not change after excluding PRD participants. The prevalence of confirmed sarcopenia in participants with any parkinsonian disorder ranged from 2 to 31.4%. Including just PD participants, the range was 10.9 to 31.4%. In studies with controls, sarcopenia was more prevalent in PD and PRD. There was a positive non-significant trend between severity of motor symptoms and prevalence of sarcopenia or components of sarcopenia. High heterogeneity precluded meta-analysis, therefore there was insufficient evidence to conclude whether sarcopenia is more prevalent in PD or PRD. Conclusions: Probable and confirmed sarcopenia are common in PD and PRD and they may be associated with disease severity. This co-occurrence supports the value of screening for sarcopenia in parkinsonian populations. [ABSTRACT FROM AUTHOR]

Sarcopenia, the age-related loss of muscle strength and mass or quality, is a common condition with major adverse consequences. Although the pathophysiology is incompletely understood, there are common mechanisms between sarcopenia and the phenomenon of accelerated ageing seen in diabetes mellitus. Drugs currently used to treat type 2 diabetes mellitus may have mechanisms of action that are relevant to the prevention and treatment of sarcopenia, for those with type 2 diabetes and those without diabetes. This review summarises shared pathophysiology between sarcopenia and diabetes mellitus, including the effects of advanced glycation end products, mitochondrial dysfunction, chronic inflammation and changes to the insulin signalling pathway. Cellular and animal models have generated intriguing, albeit mixed, evidence that supports possible beneficial effects on skeletal muscle function for some classes of drugs used to treat diabetes, including metformin and SGLT2 inhibitors. Most human observational and intervention evidence for the effects of these drugs has been derived from populations with type 2 diabetes mellitus, and there is a need for intervention studies for older people with, and at risk of, sarcopenia to further investigate the balance of benefit and risk in these target populations. Not all diabetes treatments will be safe to use in those without diabetes because of variable side effects across classes. However, some agents [including glucagon-like peptide (GLP)-1 receptor agonists and SGLT2 inhibitors] have already demonstrated benefits in populations without diabetes, and it is these agents, along with metformin, that hold out the most promise for further investigation in sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Resistance exercise is recommended for maintaining muscle mass and strength in older adults. However, little is known about exercise-induced muscle damage and recovery from resistance exercise in older adults. This may have implications for exercise prescription. This scoping review aimed to identify and provide a broad overview of the available literature, examine how this research has been conducted, and identify current knowledge gaps relating to exercise-induced muscle damage and recovery from resistance exercise in older adults. Methods: Studies were included if they included older adults aged 65 years and over, and reported any markers of exercise-induced muscle damage after performing a bout of resistance exercise. The following electronic databases were searched using a combination of MeSH terms and free text: MEDLINE, Scopus, Embase, SPORTDiscus and Web of Science. Additionally, reference lists of identified articles were screened for eligible studies. Data were extracted from eligible studies using a standardised form. Studies were collated and are reported by emergent theme or outcomes. Results: A total of 10,976 possible articles were identified and 27 original research articles were included. Findings are reported by theme; sex differences in recovery from resistance exercise, symptoms of exercise-induced muscle damage, and biological markers of muscle damage. Conclusions: Despite the volume of available data, there is considerable variability in study protocols and inconsistency in findings reported. Across all measures of exercise-induced muscle damage, data in women are lacking when compared to males, and rectifying this discrepancy should be a focus of future studies. Current available data make it challenging to provide clear recommendations to those prescribing resistance exercise for older people. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To study whether pre-fracture mobility be used to strengthen post-operative outcome prediction following hip fracture. Findings: Patients with better mobility had significantly improved outcomes and the mobility variable was able to independently predict outcomes while enhancing risk prediction when combined with the Nottingham Hip Fracture Score. Incorporating mobility assessment into risk scores may improve casemix adjustment, prognostication following hip fracture, and identify high-risk patient groups requiring enhanced post-operative care at admission. Message: Mobility information available at admission could facilitate prognostication, discharge planning, bed management and risk aversion, as well as informing discussions between clinical teams and patients about post-operative recovery. Purpose: Pre-operative scores based on patient characteristics are commonly used to predict hip fracture outcomes. Mobility, an indicator of pre-operative function, has been neglected as a potential predictor. We assessed the ability of pre-fracture mobility to predict post-operative outcomes following hip fracture. Methods: We analysed prospectively collected data from hip fracture surgery patients at a large-volume trauma unit. Mobility was classified into four groups. Post-operative outcomes studied were mortality and residence at 30 days, medical complications within 30- or 60-days post-operatively, and prolonged length of stay (LOS, ≥ 28 days). We performed multivariate regression analyses adjusting for age and sex to assess the discriminative ability of the Nottingham Hip Fracture Score (NHFS), with and without mobility, for predicting outcomes using the area under the receiver operating characteristic curve (AUROC). Results: 1919 patients were included, mean age 82.6 (SD 8.2); 1357 (70.7%) were women. Multivariate analysis demonstrated patients with worse mobility had a 1.7–5.5-fold higher 30-day mortality (p ≤ 0.001), and 1.9–3.2-fold higher likelihood of prolonged LOS (p ≤ 0.001). Worse mobility was associated with a 2.3–3.8-fold higher likelihood of living in a care home at 30-days post-operatively (p < 0.001) and a 1.3–2.0-fold higher likelihood of complications within 30 days (p ≤ 0.001). Addition of mobility improved NHFS discrimination for discharge location, AUROC NHFS 0.755 [0.733–0.777] to NHFS + mobility 0.808 [0.789–0.828], and LOS, AUROC NHFS 0.584 [0.557–0.611] to NHFS + mobility 0.616 [0.590–0.643]. Conclusion: Incorporating mobility assessment into risk scores may improve casemix adjustment, prognostication following hip fracture, and identify high-risk patient groups requiring enhanced post-operative care at admission. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. Findings: This paper provides definitions for commonly used terminology in sarcopenia in both clinical and research settings. As new methods and technologies are developed, this terminology may be expanded or refined over time. Message: We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition. Methods: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings. Results: Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size. Conclusion: As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition. [ABSTRACT FROM AUTHOR]

A growing evidence base links individual lifestyle factors to physical performance in older age, but much less is known about their combined effects, or the impact of lifestyle change. In a group of 937 participants from the MRC National Survey of Health and Development, we examined their number of lifestyle risk factors at 53 and 60–64 years in relation to their physical performance at 60–64, and the change in number of risk factors between these ages in relation to change in physical performance. At both assessments, information about lifestyle (physical activity, smoking, diet) was obtained via self-reports and height and weight were measured. Each participant's number of lifestyle risk factors out of: obesity (body mass index ≥ 30 kg/m2); inactivity (no leisure time physical activity over previous month); current smoking; poor diet (diet quality score in bottom quarter of distribution) was determined at both ages. Physical performance: measured grip strength, chair rise and standing balance times at both ages and conditional change (independent of baseline) in physical performance outcomes from 53 to 60–64 were assessed. There were some changes in the pattern of lifestyle risk factors between assessments: 227 (24%) participants had fewer risk factors by age 60–64; 249 (27%) had more. Reductions in risk factors were associated with better physical performance at 60–64 and smaller declines over time (all p < 0.05); these associations were robust to adjustment. Strategies to support reduction in number of lifestyle risk factors around typical retirement age may have beneficial effects on physical performance in early older age. [ABSTRACT FROM AUTHOR]

Objectives: To identify early nutritional risk in older populations, simple screening approaches are needed. This study aimed to compare nutrition risk scores, calculated from a short checklist, with diet quality and health outcomes, both at baseline and prospectively over a 2.5-year follow-up period; the association between baseline scores and risk of mortality over the follow-up period was assessed. Methods: The study included 86 community-dwelling older adults in Southampton, UK, recruited from outpatient clinics. At both assessments, hand grip strength was measured using a Jamar dynamometer. Diet was assessed using a short validated food frequency questionnaire; derived 'prudent' diet scores described diet quality. Body mass index (BMI) was calculated and weight loss was self-reported. Nutrition risk scores were calculated from a checklist adapted from the DETERMINE (range 0–17). Results: The mean age of participants at baseline (n = 86) was 78 (SD 8) years; half (53%) scored 'moderate' or 'high' nutritional risk, using the checklist adapted from DETERMINE. In cross-sectional analyses, after adjusting for age, sex and education, higher nutrition risk scores were associated with lower grip strength [difference in grip strength: − 0.09, 95% CI (− 0.17, − 0.02) SD per unit increase in nutrition risk score, p = 0.017] and poorer diet quality [prudent diet score: − 0.12, 95% CI (− 0.21, − 0.02) SD, p = 0.013]. The association with diet quality was robust to further adjustment for number of comorbidities, whereas the association with grip strength was attenuated. Nutrition risk scores were not related to reported weight loss or BMI at baseline. In longitudinal analyses there was an association between baseline nutrition risk score and lower grip strength at follow-up [fully-adjusted model: − 0.12, 95% CI (− 0.23, − 0.02) SD, p = 0.024]. Baseline nutrition risk score was also associated with greater risk of mortality [unadjusted hazard ratio per unit increase in score: 1.29 (1.01, 1.63), p = 0.039]; however, this association was attenuated after adjustment for sex and age. Conclusions: Cross-sectional associations between higher nutrition risk scores, assessed from a short checklist, and poorer diet quality suggest that this approach may hold promise as a simple way of screening older populations. Further larger prospective studies are needed to explore the predictive ability of this screening approach and its potential to detect nutritional risk in older adults. [ABSTRACT FROM AUTHOR]

Background: Comprehensive geriatric assessment (CGA) involves the multidimensional assessment and management of an older person. It is well described in hospital and home-based settings. A novel approach could be to perform CGA within primary healthcare, the initial community located healthcare setting for patients, improving accessibility to a co-located multidisciplinary team. Aim: To appraise the evidence on CGA implemented within the primary care practice. Methods: The review followed PRISMA recommendations. Eligible studies reported CGA on persons aged ≥ 65 in a primary care practice. Studies focusing on a single condition were excluded. Searches were run in five databases; reference lists and publications were screened. Two researchers independently screened for eligibility and assessed study quality. All study outcomes were reviewed. Results: The authors screened 9003 titles, 145 abstracts and 97 full texts. Four studies were included. Limited study bias was observed. Studies were heterogeneous in design and reported outcomes. CGAs were led by a geriatrician (n = 3) or nurse practitioner (n = 1), with varied length and extent of follow-up (12–48 months). Post-intervention hospital admission rates showed mixed results, with improved adherence to medication modifications. No improvement in survival or functional outcomes was observed. Interventions were widely accepted and potentially cost-effective. Discussion: The four studies demonstrated that CGA was acceptable and provided variable outcome benefit. Further research is needed to identify the most effective strategy for implementing CGA in primary care. Particular questions include identification of patients suitable for CGA within primary care CGA, a consensus list of outcome measures, and the role of different healthcare professionals in delivering CGA. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: Our aim was to investigate whether there has been a recent secular trend in the grip strength of older English adults, using data from the English Longitudinal Study of Ageing (ELSA). Findings: We found evidence of a slight decline in mean grip strength between 2004 and 2013. This decline is equivalent to 65-year-olds' mean strength declining to that previously seen in individuals at age 69, and did not appear to be explained by differences in lifestyle risk factors. Message: These findings are important since they raise the possibility that more recent cohorts of older people remain at similar, or possibly slightly greater, risk of the adverse consequences of weak muscle strength. Purpose: Weaker grip strength in older adults is associated with adverse health outcomes and is a key component of sarcopenia. The secular trend of grip strength is, therefore, relevant in the setting of ageing populations. A recent study suggested differences in this trend among countries in mainland Europe. We used data from the English Longitudinal Study of Ageing (ELSA) to investigate the recent secular trend of older English adults. Methods: We used data on participants aged 50–89 having their first measurement of grip strength in waves 2 (2002/2003), 4 (2008/2009) or 6 (2012/2013) of ELSA. Grip was measured using a Smedley dynamometer. We expressed grip values as Z-scores (number of standard deviations above the age and gender mean from normative data) for use in linear regression analyses examining the annual secular trend after adjustment for potential confounders. Results: We included a total of 11,476 participants from the three waves of ELSA. Grip strength declined across the three waves, with mean (SD) Z-scores of 0.01 (0.94), − 0.06 (0.97) and − 0.20 (0.98) in waves 2, 4 and 6, respectively. The annual Z-score decline after adjustments was 0.03 SDs (95% CI 0.02, 0.03) per year. Conclusion: We saw evidence of a recent slight decline in the grip strength of older English adults. Over the 9-year period of this study, the decline seen is equivalent to 65-year-olds' mean strength declining to that previously seen in individuals at age 69. Further monitoring of secular trends in grip strength and investigation of possible causes are warranted. [ABSTRACT FROM AUTHOR]

Regular physical activity (PA) is associated with reduced risk of the development and progression of musculoskeletal, metabolic and vascular disease. However, PA declines with age and this can contribute to multiple adverse outcomes. The aims of this study were to describe the relationship between accelerometer-determined PA, body composition and sarcopenia (the loss of muscle mass and function with age). Seven-day PA was measured using the GENEactiv accelerometer among 32 men and 99 women aged 74-84 years who participated in the Hertfordshire Sarcopenia Study. We measured mean daily acceleration and minutes/day spent in non-sedentary and moderate-to-vigorous physical activity (MVPA) levels. Body composition was measured by dual-energy X-ray absorptiometry, muscle strength by grip dynamometry and function by gait speed. Sarcopenia was defined according to the EWGSOP diagnostic algorithm. Men and women spent a median (inter-quartile range) of 138.8 (82, 217) and 186 (122, 240) minutes/day engaging in non-sedentary activity but only 14.3 (1.8, 30.2) and 9.5 (2.1, 18.6) min in MVPA, respectively. Higher levels of PA were associated with reduced adiposity, faster walking speed and decreased risk of sarcopenia. For example, a standard deviation (SD) increase in mean daily acceleration was associated with an increase in walking speed of 0.25 (95% CI 0.05, 0.45) SDs and a reduction in the risk of sarcopenia of 35% (95% CI 1, 57%) in fully adjusted analyses. PA was not associated with hand grip strength. Community-dwelling older adults in this study were largely sedentary but there was evidence that higher levels of activity were associated with reduced adiposity and improved function. PA at all intensity levels in later life may help maintain physical function and protect against sarcopenia. [ABSTRACT FROM AUTHOR]

Introduction: Various operational definitions have been proposed to assess the frailty condition among older individuals. Our objective was to assess how practitioners measure the geriatric syndrome of frailty in their daily routine. Methods: An online survey was sent to national geriatric societies affiliated to the European Union Geriatric Medicine Society (EUGMS) and to members of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Results: A total of 388 clinicians from 44 countries answered to the survey. Most of them were medical doctors (93%), and their primary field of practice was geriatrics (83%). Two hundred and five clinicians (52.8%) always assessed frailty in their daily practice, 38.1% reported to 'sometimes' measure it, and 9.1% never assess it. A substantial proportion of clinicians (64.9%) diagnose frailty using more than one instrument. The most widely used tool was the gait speed test, adopted by 43.8% of the clinicians, followed by clinical frailty scale (34.3%), the SPPB test (30.2%), the frailty phenotype (26.8%) and the frailty index (16.8%). Conclusion: A variety of tools is used to assess frailty of older patients in clinical practice highlighting the need for standardisation and guidelines. [ABSTRACT FROM AUTHOR]

Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcome measures to consider, have delayed research into possible therapeutic options. Most pharmacological agents investigated to date are hormonal, although new developments have seen the emergence of agents that target myostatin signalling to increase muscle mass. In this review we consider the current approaching for defining sarcopenia and discuss its epidemiology, pathogenesis, and potential therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Sarcopenia of age is prevalent and costly and proven pharmacological interventions are currently lacking. The pathophysiology of sarcopenia is incompletely understood but appears to involve multiple pathways, including inflammation, hormonal dysregulation, impaired regeneration, mitochondrial dysfunction and denervation. There are several ways in which we might select potential pharmacological interventions for testing in clinical trials. These include a 'bottom-up' approach using basic science to elucidate the molecular processes involved and identify potential targets from this knowledge-a strategy that has led to the development of myostatin inhibitors. A 'top-down' approach might use observational data to examine the association between physical function and use of certain medications, such as the association between angiotensin-converting enzyme inhibitors with slower decline in physical function. Once a pharmacological intervention has been proposed, efficacy must be demonstrated in this complex multi-morbid population. Both muscle mass and muscle function need to be measured as outcomes, but these outcomes require large sample sizes and sufficient follow-up to detect change. Biomarkers that can predict the response of sarcopenia to intervention after a short time would greatly assist our ability to select candidate interventions in short proof-of-concept trials. Further development of trial methods is required to accelerate progress in this important area of medicine for older people. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Clustering of factors linked with poor bone health is common in older adults and is associated with lower bone density and increased fracture risk in women. Purpose: Many factors are associated with bone mineral density, which in turn is strongly linked with risk of fragility fracture. We assessed how commonly clustering of risk factors occurs and related such clustering to bone mineral density in a population of older community-dwelling men and women. Method: This is a cross-sectional study with 498 men and 498 women aged 59 to 72 years, who were participants in the Hertfordshire Cohort Study, in whom incident fracture was recorded. Physical activity, diet quality, history of prior fracture, family history of fracture, cigarette and alcohol consumption and comorbidities were obtained through baseline questionnaire. Measurements of grip strength and bone mineral density of the lumbar spine and total femur were also taken. Results: Clustering of risk factors was common, with over 30 % having two or more. In women, a graded association between the number of risk factors and low bone density was seen, and strong relationships were also seen between the number of risk factors and incident fracture; women with three or more risk factors had an adjusted hazard ratio (HR) of incident fracture of 5.98 (1.67, 21.43; p = 0.006) compared to women with no risk factors; women with two risk factors had an adjusted HR of 2.97 (1.14, 7.74; p = 0.03) and those with one, 2.28 (0.90, 5.75; p = 0.08). Conclusion: Clustering of risk factors for poor bone health is common in community-dwelling older adults and is associated with increased risk of fracture and adverse bone health in women. [ABSTRACT FROM AUTHOR]

Sarcopenia is associated with adverse health outcomes. This study investigated whether skeletal muscle gene expression was associated with lean mass and grip strength in community-dwelling older men. Utilising a cross-sectional study design, lean muscle mass and grip strength were measured in 88 men aged 68-76 years. Expression profiles of 44 genes implicated in the cellular regulation of skeletal muscle were determined. Serum was analysed for circulating cytokines TNF (tumour necrosis factor), IL-6 (interleukin 6, IFNG (interferon gamma), IL1R1 (interleukin-1 receptor-1). Relationships between skeletal muscle gene expression, circulating cytokines, lean mass and grip strength were examined. Participant groups with higher and lower values of lean muscle mass ( n = 18) and strength ( n = 20) were used in the analysis of gene expression fold change. Expression of VDR (vitamin D receptor) [fold change (FC) 0.52, standard error for fold change (SE) ± 0.08, p = 0.01] and IFNG mRNA (FC 0.31; SE ± 0.19, p = 0.01) were lower in those with higher lean mass. Expression of IL-6 (FC 0.43; SE ± 0.13, p = 0.02), TNF (FC 0.52; SE ± 0.10, p = 0.02), IL1R1 (FC 0.63; SE ± 0.09, p = 0.04) and MSTN (myostatin) (FC 0.64; SE ± 0.11, p = 0.04) were lower in those with higher grip strength. No other significant changes were observed. Significant negative correlations between serum IL-6 ( R = −0.29, p = 0.005), TNF ( R = −0.24, p = 0.017) and grip strength were demonstrated. This novel skeletal muscle gene expression study carried out within a well-characterized epidemiological birth cohort has demonstrated that lower expression of VDR and IFNG is associated with higher lean mass, and lower expression of IL-6, TNF, IL1R1 and myostatin is associated with higher grip strength. These findings are consistent with a role of proinflammatory factors in mediating lower muscle strength in community-dwelling older men. [ABSTRACT FROM AUTHOR]

The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 ( APOB), rs2228671 ( LDLR) and rs629301 ( SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score = −0.02; 95 % CI = −0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits. [ABSTRACT FROM AUTHOR]

Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions. [ABSTRACT FROM AUTHOR]

Cross-sectional studies show that frailty is common in older people with cardiovascular disease. Whether older people at higher risk of developing cardiovascular disease are more likely to become frail is unclear. We used multinomial logistic regression to examine the prospective relation between Framingham cardiovascular disease risk scores and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 1,726 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing who had no history of cardiovascular disease at baseline. Men and women with higher Framingham cardiovascular risk scores were more likely to become frail over the 4-year follow-up period. For a standard deviation higher score at baseline, the relative risk ratio (95 % confidence interval) for incident frailty, adjusted for sex and baseline frailty status, was 2.76 (2.18, 3.49). There was a significant association between Framingham cardiovascular risk score and risk of pre-frailty: 1.69 (1.46, 1.95). After further adjustment for other potential confounding factors, the relative risk ratios for frailty and pre-frailty were 2.15 (1.68, 2.75) and 1.50 (1.29, 1.74), respectively. The associations were unchanged after excluding incident cases of cardiovascular disease. Separate adjustment for each component of the risk score suggested that no single component was driving the associations between cardiovascular risk score and incident pre-frailty or frailty. Framingham cardiovascular risk scores may be useful for predicting the development of physical frailty in older people. We now need to understand the biological mechanisms whereby cardiovascular risk increases the risk of frailty. [ABSTRACT FROM AUTHOR]

Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1 years). Participants completed a health questionnaire and had blood samples collected for immune-endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up ( β = 0.98, p = 0.035). This association was completely attenuated when adjusted for inflammaging burden ( p = 0.86) over the same period. Similarly, greater inflammaging burden was associated with lower grip strength at follow-up (e.g., interleukin [IL]-1 β: β = −2.18, p = 0.001). However, these associations were maintained when adjusted for telomere attrition (IL-1 β, p = 0.006). We present evidence that inflammaging may be driving telomere attrition and in part explains the associations that have previously been reported between TL and grip strength. Thus, biomarkers of physical aging, such as inflammaging, may require greater exploration. Further work is now indicated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people, but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein (CRP) and fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between CRP and fibrinogen and risk of incident frailty differed significantly by sex ( p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation (SD) increase in CRP or fibrinogen, odds ratios (95 % confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72), respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen, the fully-adjusted odds ratio (95 % confidence interval) for incident frailty in women was 1.27 (0.96, 1.69) and 1.31 (1.04, 1.67), respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers CRP and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference. [ABSTRACT FROM AUTHOR]

Suboptimal maternal nutrition and body composition are implicated in metabolic disease risk in adult offspring. We hypothesized that modest disruption of glucose homeostasis previously observed in young adult sheep offspring from ewes of a lower body condition score (BCS) would deteriorate with age, due to changes in skeletal muscle structure and insulin signaling mechanisms. Ewes were fed to achieve a lower (LBCS, n = 10) or higher (HBCS, n = 14) BCS before and during pregnancy. Baseline plasma glucose, glucose tolerance and basal glucose uptake into isolated muscle strips were similar in male offspring at 210 ± 4 weeks. Vastus total myofiber density (HBCS, 343 ± 15; LBCS, 294 ± 14 fibers/mm2, P < .05) and fast myofiber density (HBCS, 226 ± 10; LBCS 194 ± 10 fibers/mm2, P < .05), capillary to myofiber ratio (HBCS, 1.5 ± 0.1; LBCS 1.2 ± 0.1 capillary:myofiber, P < .05) were lower in LBCS offspring. Vastus protein levels of Akt1 were lower (83% ± 7% of HBCS, P < .05), and total glucose transporter 4 was increased (157% ± 6% of HBCS, P < .001) in LBCS offspring, Despite the reduction in total myofiber density in LBCS offspring, glucose tolerance was normal in mature adult life. However, such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment. [ABSTRACT FROM AUTHOR]

Summary: It is unknown whether osteoporosis is socially patterned. Using data from the Hertfordshire Cohort Study we found no consistent evidence for social inequalities in prevalent or incident fracture, bone mineral density or loss rates, or bone strength. Public health strategies for prevention of osteoporosis should focus on the whole population. Introduction: Osteoporosis and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. It is unclear whether osteoporosis and osteoporotic fracture are socially patterned. Objective: This study aims to analyse social inequalities in osteoporosis and osteoporotic fracture among the 3,225 community-dwelling men and women, aged 59-73 years, who participated in the Hertfordshire Cohort Study (HCS), UK. Methods: A panel of markers of bone health (fracture since 45 years of age; DXA bone mineral density and loss rate at the total femur; pQCT strength strain indices for the radius and tibia; and incident fracture) were analysed in relation to the social circumstances of the HCS participants (characterised at the individual level by: age left full time education; current social class; housing tenure and car availability). Results: We found little strong or consistent evidence among men, or women, for social inequalities in prevalent or incident fracture, DXA bone mineral density, bone loss rates, or pQCT bone strength, with or without adjustment for age, anthropometry, lifestyle and clinical characteristics. Reduced car availability at baseline was associated with lower pQCT radius and tibia strength strain indices at follow-up among men only ( p = 0.02 radius and p < 0.01 tibia unadjusted; p = 0.05 radius and p = 0.01 tibia, adjusted for age, anthropometry, lifestyle and clinical characteristics). Conclusions: Our results suggest that fracture and osteoporosis do not have a strong direct social gradient and that public health strategies for prevention and treatment of osteoporosis should continue to focus on the whole population. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to examine the prospective association between symptoms of anxiety and depression and risk of fracture in older people. Results showed that men, but not women, with probable anxiety at baseline had an increased risk of fracture. Introduction: The use of psychotropic drugs has been linked with an increased risk of fracture in older people, but there are indications that the conditions for which these drugs were prescribed may themselves influence fracture risk. The aim of this study was to investigate the relation between symptoms of anxiety and depression and risk of fracture in older people. The study design is a prospective cohort study. Methods: One thousand eighty-seven men and 1,050 women aged 59-73 years completed the Hospital Anxiety and Depression Scale (HADS). Data on incident fracture during an average follow-up period of 5.6 years were collected through interview and a postal questionnaire. Results: Compared to men with no or few symptoms of anxiety (score ≤7 on the HADS anxiety subscale), men with probable anxiety (score ≥11) had an increased risk of fracture: After adjustment for age and potential confounding factors, the odds ratio (OR) (95 % confidence interval) was 4.03 (1.55, 10.5). There were no associations between levels of anxiety and fracture risk in women. Few men or women had probable depression at baseline (score ≥11 on the HADS depression subscale). Amongst men with possible depression (score 8-10), there was an increased risk of fracture that was of borderline significance: multivariate-adjusted OR 3.57 (0.99, 12.9). There was no association between possible depression and fracture risk in women. Conclusions: High levels of anxiety in older men may increase their risk of fracture. Future research needs to replicate this finding in other populations and investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: There is increasing interest in physical performance as it relates to both the current and future health of older people. It is often characterised using the Short Physical Performance Battery including assessment of gait speed, chair rises and standing balance. However this battery of tests may not be feasible in all clinical settings and simpler measures may be required. As muscle strength is central to physical performance, we explored whether grip strength could be used as a marker of the Short Physical Performance Battery. Objective: To examine associations between grip strength and components of the Short Physical Performance Battery in older community dwelling men and women. Methods: Grip strength measurement and the Short Physical Performance Battery were completed in 349 men and 280 women aged 63-73 years taking part in the Hertfordshire Cohort Study (HCS). Relationships between grip strength and physical performance (6m timed-up-and-go [TUG], 3m walk, chair rises and standing balance times) were analysed using linear and logistic regression, without and with adjustment for age, anthropometry, lifestyle factors and co-morbidities. Results: Among men, a kilo increase in grip strength was associated with a 0.07s (second) decrease in 6m TUG, a 0.02s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001 for all). Among women, a kilo increase in grip strength was associated with a 0.13s decrease in 6m TUG, a 0.03s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001). Higher grip strength was associated with better balance among men (p=0.01) but not women (p=0.57). Adjustment for age, anthropometry, lifestyle and co-morbidities did not alter these results. Conclusions: Grip strength is a good marker of physical performance in this age group and may be more feasible than completing a short physical performance battery in some clinical settings. [ABSTRACT FROM AUTHOR]

Background and aims: Muscle strength mail decline with age differentially in the upper and lower limbs. This information is difficult to capture through a single measure. The present study therefore aimed to characterize the relative changes in handgrip and lower limb muscle strength with aging by expressing them as a ratio. Methods: Thirty-eight healthy volunteers aged 20-82 years performed maximal voluntary contractions (MVC) of quadriceps and handgrip using a custom- built transducer and a Jamar dynamometer respectively. Results: The grip-quadriceps ratios for young adults was similar in males and females (0.75); indicating knee extensor force exceeded grip force by approximately 25%. Ratios were increased in older adults (p=0.05), and strength of the two muscle groups was approximately equal (1.1). Pearson's correlation coefficients for grip against quadriceps strength were r=0.63 (young males), r=0.83 (young females), r=0.35 (older males) and r=0.05 (older females). Conclusions: The ratio used demonstrated clear differences between the age groups. The reduced muscle strength with increasing age was expected, but the higher grif/quadriceps strength ratios quantify a greater loss of quadriceps than grip strength with aging. It remains to be investigated whether the relatively greater rate of decline in quadriceps strength seen in healthy older people is more exaggerated in those who are frail, which would have implications for using grip strength as a physical marker of lower limb strength and function in those at risk of immobility and falls. (Aging Clin Exp Res 2012; 24: 245-250) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m² greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population. [ABSTRACT FROM AUTHOR]

Sarcopenia, a disorder that involves the generalized loss of skeletal muscle strength and mass, was formally recognized as a disease by its inclusion in the International Classification of Diseases in 2016. Sarcopenia typically affects older people, but younger individuals with chronic disease are also at risk. The risk of sarcopenia is high (with a prevalence of ≥25%) in individuals with rheumatoid arthritis (RA), and this rheumatoid sarcopenia is associated with increased likelihood of falls, fractures and physical disability, in addition to the burden of joint inflammation and damage. Chronic inflammation mediated by cytokines such as TNF, IL-6 and IFNγ contributes to aberrant muscle homeostasis (for instance, by exacerbating muscle protein breakdown), and results from transcriptomic studies have identified dysfunction of muscle stem cells and metabolism in RA. Progressive resistance exercise is an effective therapy for rheumatoid sarcopenia but it can be challenging or unsuitable for some individuals. The unmet need for anti-sarcopenia pharmacotherapies is great, both for people with RA and for otherwise healthy older adults. Sarcopenia, which involves the generalized loss of skeletal muscle strength and mass, is commonly associated with rheumatoid arthritis. In this Review, the authors discuss the epidemiology, pathophysiology and identification of rheumatoid sarcopenia and present evidence for the therapeutic roles of physical activity, nutrition and pharmacotherapy. Key points: Sarcopenia is a progressive and generalized skeletal muscle disorder that involves the accelerated loss of muscle strength and mass and affects approximately one in four people with rheumatoid arthritis (RA). Disease-specific risk factors for rheumatoid sarcopenia include high disease activity, raised inflammatory markers, long disease duration, rheumatoid factor positivity, glucocorticoid use and joint damage. Inflammatory cytokines can accelerate the development of sarcopenia through elevation of muscle proteolysis, disruption of muscle stem cell self-renewal and direct impairment of myofibre force. Muscle strength is the key marker of sarcopenia; handgrip strength can be measured in RA and specific devices are available for individuals with severe hand arthritis. Muscle mass in RA is most frequently measured with dual-energy X-ray absorptiometry, although newer techniques (ultrasonography, CT and MRI) are emerging, and panels of molecular biomarkers might prove useful in the future. Exercise is currently the most effective intervention for improving strength and muscle mass in people with RA. [ABSTRACT FROM AUTHOR]