Search

XLS file - 240K, Spreadsheet of regulated genes, primers used, geneset enrichment analysis results and meta analysis with other datasets

Purpose: The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies.Experimental Design: Microarrays were used to examine the transcriptome in single biopsies from healthy controls (n = 6) and in paired biopsies [pre-resection baseline (weight-loss 7%) and 8 month post-resection follow-up (disease-free/weight-stable for previous 2 months)] from quadriceps muscle of patients with upper gastrointestinal cancer (UGIC; n = 12).Results: Before surgery, 1,868 genes were regulated compared with follow-up (false discovery rate, 6%). Ontology analysis showed that regulated genes belonged to both anabolic and catabolic biologic processes with overwhelming downregulation in baseline samples. No literature-derived genes from preclinical cancer cachexia models showed higher expression in baseline muscle. Comparison with healthy control muscle (n = 6) revealed that despite differences in the transcriptome at baseline (941 genes regulated), the muscle of patients at follow-up was similar to control muscle (2 genes regulated). Physical activity (step count per day) did not differ between the baseline and follow-up periods (P = 0.9), indicating that gene expression differences reflected the removal of the cancer rather than altered physical activity levels. Comparative gene expression analysis using exercise training signatures supported this interpretation.Conclusions: Metabolic and protein turnover–related pathways are suppressed in weight-losing patients with UGIC whereas removal of the cancer appears to facilitate a return to a healthy state, independent of changes in the level of physical activity. Clin Cancer Res; 18(10); 2817–27. ©2012 AACR.

Key summary points Aim To assess the feasibility of conducting acute sarcopenia research in complex populations of hospitalised older adults. Findings Recruitment rates were higher in elective surgery patients compared to emergency surgery or medical patients. Drop-out rates were not affected by age or frailty of participants. Completion rates of ultrasound quadriceps were higher than other procedures. Message Acute sarcopenia research represents unique challenges but is feasible provided protocol adaptations are incorporated. Assessment of muscle quantity and quality should be included in early-stage clinical research studies to provide mechanistic insights underpinning interventions, especially where physical performance testing may not be possible or reliable., Purpose To assess feasibility of conducting acute sarcopenia research in complex populations of hospitalised older adults. Methods Patients ≥ 70 years old were recruited to three cohorts: elective colorectal surgery, emergency (abdominal) surgery, medical patients with infections. Participants were recruited to the elective cohort in preoperative assessment clinic, and acutely admitted participants from surgical and medical wards at the Queen Elizabeth Hospital Birmingham. Serial measures of muscle quantity (ultrasound quadriceps, bioelectrical impedance analysis), muscle function (hand grip strength, physical performance), and questionnaires (mini-nutritional assessment, physical function) were performed at baseline, within 7 (± 2) days of admission/surgery, and 13 (± 1) weeks post-admission/surgery. Feasibility outcomes were assessed across timepoints including recruitment and drop-out rates, and procedure completion rates. Results Eighty-one participants were recruited (mean age 79, 38.3% females). Recruitment rates were higher in elective (75%, 24/32) compared to emergency surgery (37.2%, 16/43), and medical participants (45.1%, 41/91; p = 0.003). Drop-out rates varied from 8.3 to 19.5% at 7 days, and 12.5–43.9% at 13 weeks. Age and gender did not differ between patients assessed for eligibility, approached, or recruited. Completion rates were highest for ultrasound quadriceps (98.8%, 80/81 across all groups at baseline). Gait speed completion rates were lower in medical (70.7%, 29/41) compared to elective participants (100%, 24/24) at baseline. Conclusion Higher participation refusal and drop-out rates should be expected for research involving recruitment of participants from the acute setting. Assessment of muscle quantity/quality through ultrasound is recommended in early-stage trials in the acute setting, where completion rates of physical performance testing are expected to be lower.

Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.

Background To evaluate the acceptability of handgrip strength, gait speed, quadriceps ultrasound, and Bioelectrical Impedance Analysis (BIA) to older adults conducted during and following hospitalisation. Methods Questionnaire-based study conducted upon completion of prospective cohort study, with follow-up in either Queen Elizabeth Hospital Birmingham (QEHB), UK, or participant’s own home following recent admission to QEHB. Outcome measures were acceptability as defined by total multi-domain score for each test (maximum score 35), and by frailty status. Results Forty adults aged 70 years and older admitted for emergency abdominal surgery, elective colorectal surgery, or acute bacterial infections (general medicine) participated. Handgrip strength (median 33, IQR 30–35; p = 0.001), gait speed (median 32, IQR 30–35; p = 0.002), ultrasound quadriceps (median 33, IQR 31–35; p = 0.001), and BIA (median 33.5, IQR 31–35; p = 0.001) were considered highly acceptable. Participants responded positively that they enjoyed participating in these tests, and considered these tests of importance. There was no difference in scores between tests (p = 0.166). Individual total test scores did not differ between patients with and without frailty. Qualitative data are also presented on drivers for research participation. Conclusions Handgrip strength, gait speed, ultrasound quadriceps, and BIA are acceptable tests to older adults during and following hospitalisation. Our results may serve as standards when evaluating acceptability of other tests. Trial registration Prospectively registered February 2019: https://clinicaltrials.gov/ct2/show/NCT03858192

Objective Assimilate evidence for interventions to ameliorate negative changes in physical performance, muscle strength and muscle quantity in hospitalised older adults. Methods We searched for articles using MEDLINE, Embase, CINAHL and Cochrane library using terms for randomised controlled trials, older adults, hospitalisation and change in muscle quantity, strength or physical performance. Two independent reviewers extracted data and assessed risk of bias. We calculated standardised mean differences for changes in muscle function/quantity pre- and post-intervention. Results We identified 9,805 articles; 9,614 were excluded on title/abstract; 147 full texts were excluded. We included 44 studies including 4,522 participants; mean age 79.1. Twenty-seven studies (n = 3,417) involved physical activity interventions; a variety were trialled. Eleven studies involved nutritional interventions (n = 676). One trial involved testosterone (n = 39), two involved Growth Hormone (n = 53), one involved nandrolone (n = 29), and another involved erythropoietin (n = 141). Three studies (n = 206) tested Neuromuscular Electrical Stimulation. Evidence for effectiveness/efficacy was limited. Strongest evidence was for multi-component physical activity interventions. However, all studies exhibited at least some concerns for overall risk of bias, and considering inconsistencies of effect sizes across studies, certainty around true effect sizes is limited. Conclusion There is currently insufficient evidence for effective interventions to ameliorate changes in muscle function/quantity in hospitalised older adults. Multiple interventions have been safely trialled in heterogeneous populations across different settings. Treatment may need to be stratified to individual need. Larger scale studies testing combinations of interventions are warranted. Research aimed at understanding pathophysiology of acute sarcopenia will enable careful risk stratification and targeted interventions.

This study aims to investigate the effects of fish oil supplementation on the muscle adaptive response to resistance exercise training, physical performance and serum levels of inflammatory cytokines in sarcopenic older women. A randomised, double-blind, placebo-controlled trial is performed with thirty-four sarcopenic women (2010 European Consensus of Sarcopenia), aged ≥ 65 years. The participants are allocated into the following two groups: Exercise and Fish Oil (EFO) and Exercise and Placebo (EP). Both groups undertook a resistance exercise programme over 14 weeks. All participants are instructed to ingest 4 g/day of food supplements; the EP group received sunflower oil capsules, and the EFO group, fish oil capsules. The cross-sectional area (CSA) of the quadriceps muscle is calculated using magnetic resonance imaging (MRI). The strength of the lower limbs is measured using isokinetic dynamometry. Both groups show improvements in CSA and strength after the intervention. Changes in EFO are significantly greater compared with EP for muscle strength (peak torque, 19.46 Nm and 5.74 Nm, respectively, p < 0.001). CSA increased after the intervention in both groups (EFO; 6.11% and EP; 2.91%), although there is no significant difference between the groups (p = 0.23). There are no significant intra-group, inter-group or time differences in any of the cytokines measured. The use of fish oil supplementation potentiates the neuromuscular response to the anabolic stimulus from training, increasing muscle strength and physical performance in sarcopenic older women.

The world’s population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multi-dimensional and dynamic condition characterised by declines in reserve and function across multiple physiologic systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.

Background Frailty is a common and clinically significant condition among geriatric populations. Although well-evidenced pooled estimates of the prevalence of frailty exist within various settings and populations, presently there are none assessing the overall prevalence of frailty among geriatric hospital inpatients. The purpose of this review was to systematically search and analyse the prevalence of frailty among geriatric hospital inpatients within the literature and examine its associations with national economic indicators. Methods Systematic searches were conducted on Ovid, Web of Science, Scopus, CINAHL Plus, and the Cochrane Library, encompassing all literature published prior to 22 November 2018, supplemented with manual reference searches. Included studies utilised a validated operational definition of frailty, reported the prevalence of frailty, had a minimum age ≥ 65 years, attempted to assess the whole ward/clinical population, and occurred among hospital inpatients. Two reviewers independently extracted data and assessed study quality. Results Ninety-six studies with a pooled sample of 467,779 geriatric hospital inpatients were included. The median critical appraisal score was 8/9 (range 7–9). The pooled prevalence of frailty, and pre-frailty, among geriatric hospital inpatients was 47.4% (95% CI 43.7–51.1%), and 25.8% (95% CI 22.0–29.6%), respectively. Significant differences were observed in the prevalence of frailty stratified by age, prevalent morbidity, ward type, clinical population, and operational definition. No significant differences were observed in stratified analyses by sex or continent, or significant associations between the prevalence of frailty and economic indicators. Conclusions Frailty is highly prevalent among geriatric hospital inpatients. High heterogeneity exists within this setting based on various clinical and demographic characteristics. Pooled estimates reported in this review place the prevalence of frailty among geriatric hospital inpatients between that reported for community-dwelling older adults and older adults in nursing homes, outlining an increase in the relative prevalence of frailty with progression through the healthcare system.

Protein ingestion is a potent stimulator of skeletal muscle protein synthesis (MPS). However, older adults demonstrate resistance to anabolic stimuli. Some evidence has demonstrated that a larger acute protein dose is required in older compared to younger adults to elicit the same synthetic response, suggesting that older adults should be consuming higher habitual dietary protein to optimise muscle mass. However, limited research has explored dietary habits in different age groups or the relationship between habitual dietary intake and mechanistic physiological parameters associated with muscle mass and function. This work investigated the effect of habitual dietary intake in young (n = 10, 25.9 (3.2y)) and older (n = 16, 70.2 (3.2y)) community-dwelling adults (16:10 male: female) on physiological muscle parameters. Dietary intake was assessed using four-day diet diaries. Post-absorptive MPS and MPS responses to feeding (4.25x basal metabolic rate; 16% protein) were determined in muscle biopsies of the m. vastus lateralis via stable isotope tracer ([1, 2−13C2]-leucine) infusions with mass-spectrometric analyses. Body composition was measured by dual-energy x-ray absorptiometry. Whole body strength was assessed via 1-repetition maximum assessments. No significant differences in habitual dietary intake (protein, fat, carbohydrate and leucine as g.kgWBLM−1.day−1) were observed between age groups. Whole-body lean mass (61.8 ± 9.9 vs. 49.8 ± 11.9 kg, p = 0.01) and knee-extensor strength (87.7 ± 28.3 vs. 56.8 ± 16.4 kg, p = 0.002) were significantly higher in young adults. Habitual protein intake (g.kg−1.day−1) was not associated with whole-body lean mass, upper-leg lean mass, whole-body strength, knee-extensor strength, basal MPS or fed-state MPS across both age groups. These findings suggest that differences in muscle mass and strength parameters between youth and older age are not explained by differences in habitual dietary protein intake. Further research with a larger sample size is needed to fully explore these relationships and inform on interventions to mitigate sarcopenia development.

Background Osteoarthritis is a prevalent condition in older adults that causes many patients to require a hip or knee replacement. Reducing patients’ sedentariness prior to surgery may improve physical function and post-operative outcomes. Methods We conducted a pragmatic randomised-controlled feasibility study with 2:1 allocation into intervention or usual care groups. The intervention, based on Self-Determination Theory, involved techniques to reduce sedentary behaviour, including motivational interviewing, setting of behavioural goals, and more. The primary outcome was feasibility, assessed using mixed methods. We included exploratory measures to inform a future definitive trial, such as ActivPal3 accelerometry to measure movement, the Short Physical Performance Battery (SPPB), Basic Psychological Needs, and cardiometabolic biomarkers. Assessments were at baseline, 1-week pre-surgery, and 6-week post-surgery. Results We recruited 35 participants aged ≥ 60 years approximately 8 weeks before hip or knee arthroplasty. Participant uptake rate was 14.2%, and retention rate 85.7%. Participants were very satisfied with the study which was found to be feasible with some modifications. Exploratory within-group comparisons found that the intervention has potential to improve SPPB by 0.71 points from baseline to pre-surgery, a clinically significant increase, and reduce sedentary time by up to 66 min d−1. Conclusion In this older surgical population, it is feasible to use behavioural techniques to displace sedentary time to activity and to conduct a trial spanning the period of surgical intervention. This may improve physical function and surgical outcomes. The INTEREST intervention is now ready for evaluation in a full-scale randomised-controlled trial. Registration This trial was registered on Clinicaltrials.gov on 13/11/2018. ID: NCT03740412.

Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.

Background Lower-limb osteoarthritis (OA) causes high levels of pain and disability. Physiotherapists are the primary healthcare provider of non-pharmacological treatments, and incorporate strategies to optimise physical activity (PA) to aid patients with lower-limb OA to moderate their clinical symptoms. However, patients with lower-limb OA have low adherence to PA recommendations both during treatment and after discharge. This study aimed to use knowledge of identified barriers and facilitators to physiotherapy prescribed PA (during treatment and post-discharge) to develop a theoretically informed intervention to optimise adherence to PA for patients with lower-limb OA during treatment and post-discharge. Methods 1) A purposive sample of 13 patients with lower-limb OA participated in semi-structured interviews following physiotherapy treatment. Inductive analysis identified themes/subthemes reflecting barriers and facilitators to physiotherapist prescribed PA, which were organised deductively according to personal factors, treatment and post-discharge phases. 2) Themes/subthemes were mapped onto the theoretical domains framework (TDF). 3) Behaviour change techniques (BCTs) were coded from the key identified domains and a theoretically informed physiotherapy intervention addressing barriers and using facilitators, was developed. Results Themes of patient confidence, mind-set, motivation, OA symptoms and PA experiences were primary personal factors that influenced PA adherence; with the TDF domain ‘Beliefs about capabilities’ most important to target. During treatment, the theme of routine formation was the major driver of personal factors; and primarily influenced by developing a positive physiotherapist-patient relationship. Post-discharge, physical factors, psychosocial factors and ongoing access to resources were important themes influencing PA maintenance. ‘Environmental context and resources’ and ‘social influences’ emerged as the key TDF domains to target during treatment and post-discharge. The proposed theoretically informed intervention included 26 BCTs delivered across conceptual phases of adoption, routine formation, and maintenance. Conclusion A theoretically informed physiotherapy intervention was proposed to optimise PA adherence in patients with lower-limb OA. The included BCTs primarily target patients’ perceived beliefs about their capabilities, by developing a PA routine during treatment and facilitating appropriate psychosocial support and access to resources for PA maintenance post-discharge. The feasibility of delivering the intervention in clinical practice will now be evaluated.

Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and bone health (bone mineral density; BMD) in older adults. The purpose of this review is to examine associations of SB with BMD in older adults. Five electronic databases were searched: Web of Science (Core Collection); PubMed; EMBASE; Sports Medicine and Education and PsycInfo. Inclusion criteria were healthy older adults mean age ≥ 65 years; measured SB and measured BMD using dual-energy X-ray absorptiometry. Quality was assessed using National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After excluding duplicates 17813 papers were assessed; 17757 were excluded on title/abstract, 49 at full text, resulting in two prospective and five cross-sectional observational studies reviewed. Four were rated 'good' and three were rated 'fair' using the quality assessment criteria. Findings varied across the studies and differed by gender. In women, four studies reported significant positive associations of SB with BMD at different sites, and two found significant negative associations. Five studies which examined both men and women, men reported negative or no associations of SB with femoral neck, pelvic, whole body, spine or leg BMD. Whilst these findings suggest differences between men and women in the associations of SB with BMD, they may be due to the varying anatomical sections examined for BMD, the different methods used to measure SB, the varied quality of the studies included and the limited number of published findings.

NEW FINDINGS What is the central question of this study? How does peripheral nerve stimulation (PNS) compare with neuromuscular electrical stimulation (NMES) used clinically to reduce muscle atrophy? What is the main finding and its importance? NMES resulted in progressive increases in M-wave duration and delay of muscle relaxation throughout a single stimulation protocol, findings not observed with PNS. This suggests PNS recruits from a wider pool of muscle fibres/motor units, providing a more favourable alternative to NMES for rehabilitation intervention. ABSTRACT Neuromuscular electrical stimulation (NMES) is increasingly viewed as a central tenet to minimise muscle loss during periods of disuse/illness - typically applied directly over a muscle belly. Peripheral nerve stimulation (PNS) is afforded less attention, despite providing a more global contractile stimulus to muscles. We investigated NMES versus PNS in relation to performance fatigability and peripheral contributions to voluntary force capacity. Two fatigue protocols were assessed separately: (1) over-quadriceps NMES and (2) peripheral (femoral) nerve stimulation (PNS). Before and after each session, a maximal voluntary contraction (MVC) was performed to assess force loss. Knee-extensor force was measured throughout to assess contractile function in response to submaximal electrical stimulation, and M-wave features quantified myoelectrical activity. NMES and PNS induced similar voluntary (MVC, NMES: -12 ± 9%, PNS: -10 ± 8%, both P

The COVID-19 pandemic has had a devastating global impact, with older adults being most at risk of death from the disease. However, acute sarcopenia occurs in survivors of COVID-19; older adults and the most critically unwell patients are the most at risk. Acute sarcopenia is an under-recognised condition of acute muscle insufficiency, defined by declines in muscle function and/or quantity within six months, usually following a stressor event. This commentary reviews definition and mechanisms of acute sarcopenia in COVID-19 and suggests recommendations for research and clinical practice. Research should now focus on the longer-term consequences of acute sarcopenia in patients who have suffered from COVID-19. At the same time, clinicians need to be increasingly aware of the condition, and measurements of muscle strength, quantity, and physical performance should be embedded into clinical practice. Clinicians should consider the risks of acute sarcopenia when weighing up the risks and benefits of treatment (e.g. dexamethasone), and instigate multidisciplinary treatment including dietetics input.

The spread of novel SARS-CoV-2 virus, and the disease COVID-19 that is caused by SARS-CoV-2, continues apace. Saving lives and slowing the worldwide pandemic remain of utmost importance to everyone: the public, healthcare professionals, scientists, industry and governments. It is absolutely essential that advice given to the public is evidence-based, accurate and timely; anything less would mislead and has the potential to cause harm. Popular information channels, such as social media platforms, have been rife with misinformation that has been perpetuated by fear and uncertainty. This has been the case particularly for diet and lifestyle advice. There are recommendations for the prevention of the spread of COVID-19 from the WHO,1 the UK,2 Irish3 and USA4 governments and the European Commission,5 as well as public health and healthcare agencies, including key direction on self-isolation.6 This short original report aims to provide a balanced scientific view on vitamin D and SARS-CoV-2 virus/COVID-19 disease. It provides a succinct summary of the current scientific evidence of associations between vitamin D, influenza, upper respiratory tract infections (URTIs) and immune health. Importantly, the paper concludes with lifestyle strategies for avoiding vitamin D deficiency and ensuring a healthy balanced diet at any time, including during the current pandemic. The overarching messages are as follows: (1) Vitamin D is essential for good health. (2) Many people, particularly those living in northern latitudes (such as the UK, Ireland, Northern Europe, Canada and the northern parts of the USA, northern India and China), have poor vitamin D status, especially in winter or if confined indoors. (3) Low vitamin D status may be exacerbated during this COVID-19 crisis (eg, due to indoor living and hence reduced sun exposure), and anyone who is self-isolating with limited access to sunlight is advised to take a vitamin D supplement according to their government’s recommendations for the general population (ie, 400 IU/day for the UK7 and 600 IU/day for the USA (800 IU for >70 years))8 and the European Union (EU).9 (4) There is no strong scientific evidence to show that very high intakes (ie, mega supplements) of vitamin D will be beneficial in preventing or treating COVID-19. (5) There are evidenced health risks with excessive vitamin D intakes especially for those with other health issues such as a reduced kidney function.

Introduction The extent to which chronic exercise training preserves age-related decrements in physical function, muscle strength, mass and morphology is unclear. Our aim was to conduct a systematic review of the literature to determine to what extent chronically trained master athletes (strength/power and endurance) preserve levels of physical function, muscle strength, muscle mass and morphology in older age, compared with older and younger controls and young trained individuals. Methods The systematic data search included Medline, EMBASE, SPORTDiscus, CINAHL and Web of Science databases. Inclusion criteria i) master athletes mean exercise training duration ≥20 years ii) master athletes mean age of cohort >59 years) iii) at least one measurement of muscle mass/volume/fibre-type morphology and/or strength/physical function. Results Fifty-five eligible studies were identified. Meta-analyses were carried out on maximal aerobic capacity, maximal voluntary contraction and body composition. Master endurance athletes (42.0 ± 6.6 ml kg−1 min−1) exhibited VO2max values comparable with young healthy controls (43.1 ± 6.8 ml kg−1 min−1, P = .84), greater than older controls (27.1 ± 4.3 ml kg−1 min−1, P Conclusion Despite advancing age, this review suggests that chronic exercise training preserves physical function, muscular strength and body fat levels similar to that of young, healthy individuals in an exercise mode-specific manner.

First paragraph: Current demographic trends indicate that by the year 2020, almost one in five of the European population will be aged 65 years or over. Although life expectancy is increasing by 2 years per decade, the period of life spent in good health is not keeping pace and most Europeans spend their last decade in poor health. Consequently, there is an urgent need to understand how lifestyle factors can influence age-related changes from gene to society level and how they may be integrated into a net effect of healthy ageing. It is also crucial to develop and validate interventions and health policies to ensure that more of our older adults have a healthy and active later life. This is an urgent and cross-cutting research priority in Europe, and to achieve this, it is vital to increase research capacity in this area to push forward the frontiers of scientific understanding. The Horizon 2020 funded Marie Curie Sklodowska Innovative Training Network—PANINI is addressing this capacity issue by focusing on research and training in two major interacting lifestyle factors with impact at multiple levels, namely, physical activity and nutrition.

Objectives This article reviews the effects of physical activity (PA) interventions on social isolation, loneliness or low social support in older adults. Design Systematic review and meta-analysis of randomised controlled trials (RCTs). Method MEDLINE, EMBASE, PsycINFO, the Cochrane CENTRAL, CINAHL, were screened up to February 2017. RCTs comparing PA versus non-PA interventions or control (sedentary) condition were included. Risk of bias was assessed using the 12 criteria Cochrane Review Book Group risk of bias. The outcome measures were: social isolation, loneliness, social support, social networks, and social functioning. Standardised mean differences (SMDs) with associated 95% confidence intervals (CIs) were calculated for continuous outcomes. Meta-analysis was performed using a random effects model. Results The search strategy identified 38 RCTs, with a total of 5288 participants, of which 26 had a low risk of bias and 12 had a high risk of bias. Meta-analysis was performed on 23 RCTs. A small significant positive effect favouring the experimental condition was found for social functioning (SMD = 0.30; 95% CI, 0.12 to 0.49; P = 0.001) with strongest effects obtained for PA interventions, diseased populations, group exercise setting, and delivery by a medical healthcare provider. No effect of PA was found for loneliness, social support, or social networks. Conclusion This review shows, for social functioning, the specific aspects of PA interventions can successfully influence social health. PA did not appear to be effective for loneliness, social support and social networks.

Introduction Sarcopenia is a progressive loss in muscle mass, strength and function, the adverse consequences of which are severe, affecting quality of life and placing an increasing burden on social and healthcare systems. Vitamin D status is known to be associated with markers of sarcopenia, namely muscle mass, strength and function. Also, resistance exercise training (RET) is currently the only proven intervention to treat sarcopenia. However, very little data exist on the influence of combining the two interventions of vitamin D supplementation and resistance exercise training, although a recent systematic review provides tentative support for the current study’s hypothesis that the combined intervention may further improve musculoskeletal function above exercise training alone. The aim of the present study is to determine whether vitamin D3 supplementation is any more effective in improving musculoskeletal function when combined with RET compared with exercise training alone in older adults. Methods and analysis This double-blinded randomised placebo-controlled trial will recruit a target of 127 eligible men and women aged ≥65 years living independently or in sheltered housing within the Birmingham area to two groups: (1) 6 months RET and placebo or (2) 6 months RET and 800 IU/d vitamin D3. Measures of muscle power (Nottingham Power Rig), body composition (dual energy X-ray absorptiometry), muscle function (short physical performance battery, timed up and go), falls and fractures as events will be assessed. Assessments will take place at baseline and postintervention, with intermittent monitoring of bone turnover, calcium and vitamin D. The primary outcome will be lower limb extensor power output. Analyses of within-group changes and between-group differences in outcome measures are planned. Ethics and dissemination The EXVITD study has ethical approval granted by the Black Country National Health Service Research Ethics Committee (14/WM/1220). Results of this trial will be submitted for publication in peer-reviewed journals and presented at conferences. The study is being conducted according to the principles of the Declaration of Helsinki. Trial registration number NCT02467153; Post-results.

IntroductionSarcopenia is a progressive loss in muscle mass, strength and function, the adverse consequences of which are severe, affecting quality of life and placing an increasing burden on social and healthcare systems. Vitamin D status is known to be associated with markers of sarcopenia, namely muscle mass, strength and function. Also, resistance exercise training (RET) is currently the only proven intervention to treat sarcopenia. However, very little data exist on the influence of combining the two interventions of vitamin D supplementation and resistance exercise training, although a recent systematic review provides tentative support for the current study’s hypothesis that the combined intervention may further improve musculoskeletal function above exercise training alone. The aim of the present study is to determine whether vitamin D3supplementation is any more effective in improving musculoskeletal function when combined with RET compared with exercise training alone in older adults.Methods and analysisThis double-blinded randomised placebo-controlled trial will recruit a target of 127 eligible men and women aged ≥65 years living independently or in sheltered housing within the Birmingham area to two groups: (1) 6 months RET and placebo or (2) 6 months RET and 800 IU/d vitamin D3. Measures of muscle power (Nottingham Power Rig), body composition (dual energy X-ray absorptiometry), muscle function (short physical performance battery, timed up and go), falls and fractures as events will be assessed. Assessments will take place at baseline and postintervention, with intermittent monitoring of bone turnover, calcium and vitamin D. The primary outcome will be lower limb extensor power output. Analyses of within-group changes and between-group differences in outcome measures are planned.Ethics and disseminationThe EXVITD study has ethical approval granted by the Black Country National Health Service Research Ethics Committee (14/WM/1220). Results of this trial will be submitted for publication in peer-reviewed journals and presented at conferences. The study is being conducted according to the principles of the Declaration of Helsinki.Trial registration numberNCT02467153; Post-results.

Determining the effect of ageing on thigh muscle stiffness using magnetic resonance elastography (MRE) and investigate whether fat fraction and muscle cross-sectional area (CSA) are related to stiffness. Six healthy older adults in their eighth and ninth decade and eight healthy young men were recruited and underwent a 3 T MRI protocol including MRE and Dixon fat fraction imaging. Muscle stiffness, fat fraction and muscle CSA were calculated in ROIs corresponding to the four quadriceps muscles (i.e. vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), rectus femoris (RF)), combined quadriceps, combined hamstrings and adductors and whole thigh. Muscle stiffness was significantly reduced (p p = 0.573) and RF (p = 0.081). Similarly, mean fat fraction was significantly increased (p p = 0.059) and VL muscle groups (p = 0.142). Muscle CSA was significantly reduced in older participants in the VM (p = 0.003) and the combined quadriceps (p = 0.001), hamstrings and adductors (p = 0.008) and whole thigh (p = 0.003). Over the whole thigh, stiffness was significantly negatively correlated with fat fraction (r = − 0.560, p = 0.037) and positively correlated with CSA (r = 0.749, p = 0.002). Stepwise regression analysis revealed that age was the most significant predictor of muscle stiffness (p = 0.001). These results suggest that muscle stiffness is significantly decreased in healthy older adults. Muscle fat fraction and muscle CSA are also significantly changed in older adults; however, age is the most significant predictor of muscle stiffness.

Background There are limited longitudinal data regarding nutrient intake, nutritional status and physical function in community-dwelling ethnically diverse older adults. This study explored these variables and their relationship at baseline (n=100) and 8-months’ follow-up (n=81) among community-dwelling ethnically diverse older adults (≥60 years) in Birmingham, United Kingdom.Methods Multiple-pass 24-hour dietary recalls and the Mini Nutritional Assessment-Short Form assessed nutritional intake and status, respectively. Short Physical Performance Battery (SPPB) and handgrip strength measured physical function. Linear and multinomial regressions were used to predict relationships between physical function, nutritional status and nutrient intake.Results Participants at baseline (n=100) and 8-months’ follow-up (n=81). Mean (SD) age was 70 (8.1) years (60% male), with 62% being obese. Decreases in intakes of vitamin B6, vitamin B1, iron, folate, and magnesium occurred over time. Daily intake of all micronutrients except vitamin B12, phosphorus and manganese were below the Recommended Nutrient Intakes (RNI). SPPB (Z=-4.01, p

Ethnic minorities have a high prevalence of non-communicable diseases relating to unhealthy lifestyle practices. Several factors have been identified as influencing unhealthy lifestyle practices among this population, however, there is little evidence about how these factors differ among a heterogeneous sample living in a super-diverse city. This study aimed to: (1) identify and compare factors influencing eating behaviours and physical function among ethnic older minorities living in Birmingham, United Kingdom, and (2) understand how these factors and their association with healthy eating and physical function changed over 8-months. An in-depth interviewing approach was used at baseline (n = 92) and after 8-months (n = 81). Interviews were transcribed verbatim and analysed using directed content analysis. Healthy eating was viewed as more important than, and unrelated to, physical function. Personal, social and cultural/environmental factors were identified as the main factors influencing eating behaviours and physical function, which differed by ethnicity, age, and sex. At 8-month interviews, more men than women reported adverse changes. The study provides unique and useful insights regarding perceived eating behaviours and physical function in a relatively large and diverse sample of older adults that can be used to design new, and adapt existing, culturally-tailored community interventions to support healthy ageing.

Background Osteoarthritis is a highly prevalent condition in older adults, that causes many sufferers to require a hip or knee replacement in order to improve their quality of life and reduce pain. Individuals waiting for hip or knee replacements are often highly sedentary; thus, it is pertinent to assess whether reducing their sedentariness prior to surgery may aid in improving post-operative outcomes. Methods/design The study will be a randomised controlled feasibility trial design, with 2:1 randomisation into an intervention and usual care group respectively. A target of 45 patients aged 60 years or older waiting for elective hip and knee replacements will be recruited from Russells Hall Hospital, Dudley, UK, approximately 8–10 weeks before surgery. The intervention, informed by Self-Determination Theory (SDT), will be composed of multiple behaviour change techniques, namely, motivational interviewing, feedback on current objectively measured sedentary behaviour and activity, goal-setting, environmental modification, self-monitoring, and social support. Assessments will occur at baseline, 1 week pre-surgery, and 6 weeks post-surgery. The primary outcome will be the feasibility of intervention delivery and of the trial procedures, assessed quantitatively based on rates of recruitment, retention, measures-completion, and intervention fidelity assessment, and with mixed-methods assessment of acceptability, practicality, adaption, satisfaction, and safety. Exploratory outcomes will include physical function, cardiometabolic biomarkers, measurement of SDT constructs, and both objective and subjective measurement of physical activity and sedentariness. The study will last up to 18 weeks per participant. No formal between-group comparisons are planned, but the variance in within-group changes and differences between groups in outcome measures will be explored and reported with 95% confidence intervals. Discussion This is the first study assessing the feasibility of an intervention to reduce sedentary behaviour in older adults with mobility limitations, and the first to assess whether such a reduction could work in a prehabilitative context prior to surgery. The results of this study will help inform the design of a definitive randomised controlled trial. Trial registration This trial is registered on Clinicaltrials.gov. Registration number: NCT03740412. Date of registration: 13/11/2018. Electronic supplementary material The online version of this article (10.1186/s40814-019-0437-2) contains supplementary material, which is available to authorized users.

Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting.

IntroductionThe improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects.ObjectiveOur primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens.Methods and analysisA prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16–50 years with an injury severity score ≥16, will be recruited.Ethics and disseminationThis protocol was approved by the West Midlands – Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences.Trial registrationThis trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158).Trial progressionThe study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.

Background Cancer cachexia (cancer-induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age-related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early. Methods We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH-MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy. Results We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age-related muscle loss (aka age-related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration. Conclusions The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature.

The study aim was to comprehensively assess physiological function and muscle morphology in chronically trained older individuals against untrained young and older individuals. In a cross-sectional design, 15 young untrained controls (YC) (20 ± 2.7 years, 78.9 ± 13.3 kg), 12 untrained older controls (OC) (69.8 ± 4.1 years, 77.5 ± 14.2 kg), and 14 endurance-trained master athletes (MA) (67.1 ± 4.1 years, 68.7 ± 6.5 kg) underwent assessments of body composition, aerobic capacity, strength, muscle architecture, and fiber-type morphology. Skeletal muscle index was lower and body fat greater in OC versus MA. Estimated VO2max (mL·kg−1·minute−1) was similar between MA and YC, but lower in OC. Isometric leg strength normalized to fat-free mass was similar between groups, whereas normalized isometric arm strength was greater in YC than MA. Myosin heavy chain (MHC) I fiber area was greater in MA than OC, while MHC II fiber area was greater in YC than OC. MHC II fiber myonuclear domain size was greater in YC than OC and MA, whereas MA had greater MHC I and MHC II fiber capillarization than OC and YC. Satellite cell content was similar between groups. Chronic endurance training enhances indices of muscle morphology and improves body composition and aerobic capacity in older age, with potentially important implications for healthspan extension.

Background Low quality social relationships in older adults are strongly associated with feelings of loneliness. Physical activity interventions could reduce loneliness and improve psychological well-being, among other health benefits. The aim of this study was to examine the feasibility of a Physical Activity Intervention for Loneliness (PAIL) in community-dwelling older adults at risk of loneliness. Methods The PAIL feasibility study was a 12-week randomized controlled feasibility trial (RCT) conducted in Birmingham, United Kingdom, from February 2018 to August 2018, and ran in two waves of data collection. Eligible participants were community-dwelling adults aged 60 years and older, sedentary (less than 20 min of moderate-to-vigorous PA (MVPA) a week), and at risk of loneliness. The intervention included once-weekly group walk and health education workshop up to 90 min per session in total, with a wait-listed (WL) control group. The primary feasibility outcomes were to estimate recruitment, retention rates and adherence to the intervention. Secondary outcome measures (not blinded assessment) were body mass index, blood pressure, physical activity and psychosocial variables. Process and outcome evaluations were conducted using focus groups interviews. The recruitment and retention progression criteria for the definitive large-scale RCT was set a-priori. Results Forty-eight participants were recruited over 4 months with a recruitment rate of 25% (48/195); 52% (25/48) met the inclusion criteria and 100% (25/25) were randomised into the intervention (n = 12) and WL control groups (n = 13). Participants were 25 older adults (mean (SD) 68.5(8.05) years), 14 (56%) female, and 18 (72%) white. At 12 weeks, 10/12 (83.3%) intervention and 10/13 (76.9%) control participants completed the final assessments. The average attendance rate was 58.3% for the intervention group (range 33.0%-75.0%) and 42.3% (range 23.1%–69.2%) among controls. The a priori recruitment and retention criteria for progression were not met. No serious adverse events occurred. The focus group results identified three themes which showed overall positive experiences of participation in PAIL in terms of (1) study design and intervention; (2) walking sessions; and (3) health education workshops. Conclusions The findings suggest that community-dwelling older adults at risk of loneliness found the intervention and measures acceptable and could safely participate. However, a more extensive and robust strategy would be needed to support adequate recruitment of lonely older adults and adherence into a definitive RCT. Trial registration Clinicaltrials.gov, NCT03458793

Severe injuries are the major cause of death in those aged under 40, mainly due to road traffic collisions. Endocrine, metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing, repair and regeneration mechanisms. However, depending on age and sex, the response to injury and patient prognosis differ significantly. Glucocorticoids are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEAS). The balance of these steroids after injury appears to influence outcomes in injured humans, with high cortisol: DHEAS ratio associated with increased morbidity and mortality. Animal models of trauma, sepsis, wound healing, neuroprotection and burns have all shown a reduction in pro-inflammatory cytokines, improved survival and increased resistance to pathological challenges with DHEA supplementation. Human supplementation studies, which have focused on post-menopausal females, older adults, or adrenal insufficiency have shown that restoring the cortisol: DHEAS ratio improves wound healing, mood, bone remodelling and psychological well-being. Currently, there are no DHEA or DHEAS supplementation studies in trauma patients, but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.

Introduction Knee osteoarthritis (OA) is the most common chronic illness among older adults. Up to the submission date of this protocol, there are no published UK studies reporting the efficacy of a combined intervention programme of physical activity and dietary restriction on the musculoskeletal function of obese older adults with knee OA in spite of the clinical recommendation for exercise and diet for people with knee OA. The aim of this study is to assess the feasibility and acceptability of a combined dietary restriction and physical activity intervention programme and collect preliminary data. Method and analysis This single-arm intervention study is scheduled to begin in September 2017 and conclude in November 2018. It will take place at the Royal Orthopaedic Hospital (ROH), Birmingham and the School of Sport, Exercise and Rehabilitation Sciences (SportExR), University of Birmingham. Participants will receive a physiotherapy usual care programme for knee OA for 1 month, after which they will continue to exercise in their local gym/leisure facility for 3 months. Participants will also follow dietary restriction throughout the 4-month intervention. Mixed analysis techniques will be used to analyse the quantitative and qualitative outcome measures. Ethics and dissemination It is approved by ROH R&D Foundation Trust and the Health Research Authority. The Consort Guidelines and checklist will be reviewed prior to generating any publications for the trial to ensure they meet the standards required for submission to high-quality peer-reviewed journals. Trial registration number ISRCTN12906938.