Accelerated aging of skeletal muscle and the immune system in patients with chronic liver disease.

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at -3.0 ± 3.2 years, p = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) (p = 0.01) and nonalcoholic fatty liver disease (NAFLD) (p = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup (p = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge (p < 0.0001), DunedinPACE (p < 0.0001), or Hannum (p = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls (p < 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes.

Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.

NEW FINDINGS: What is the central question of this study? To what extent does musculoskeletal impairment occur (i.e., muscle mass, quality and function) in patients with end stage liver disease (ESLD) by comparison to a healthy age/sex-matched control group? What is the main finding and its importance? Muscle mass, quality and function are impaired in patients with ESLD (compared to age/sex matched controls). Importantly, greater impairments were seen in lower limb compared to arm and trunk muscle groups. These findings may suggest that there should be greater consideration of muscle health in functionally relevant lower limb muscle groups. ABSTRACT: Sarcopenia is associated with reduced quality of life and increased mortality in patients with end stage liver disease (ESLD). Historically, sarcopenia identification in ESLD utilised L3 skeletal muscle index (SMI). There are few data on muscle quality and function within lower limb muscle groups with high functional relevance. The aim of this prospective case-control study was to evaluate the quadriceps muscle in patients with ESLD. Muscle mass and quality were evaluated using MRI (quadriceps anatomical cross sectional area (ACSA), quadriceps volume index, L3 SMI, quadriceps intermuscular adipose tissue (IMAT)), mid-arm muscle circumference (MAMC) and ultrasonography (vastus lateralis (VL) thickness and quadriceps ACSA). Muscle strength/function was assessed by handgrip strength, peak quadriceps isokinetic torque and chair rise time. Thirty-nine patients with ESLD (55 years, 61% male, 48% alcoholic related liver disease (ArLD), 71% Child-Pugh B/C) and 18 age/sex-matched healthy control participants (HC) were studied. Quadriceps mass was significantly reduced in ESLD versus HC (-17%), but L3 SMI and MAMC were unchanged. Quadriceps IMAT percentage was increased in ESLD (+103%). Handgrip strength (-15%), peak isokinetic torque (-29%), and chair rise time (+56%) were impaired in ESLD. Ultrasound measures of VL thickness (r = 0.56, r = 0.57, r = 0.42) and quadriceps ACSA (r = 0.98, r = 0.86, r = 0.67) correlated to MRI quadriceps ACSA, quadriceps volume and L3 SMI, respectively. Quadriceps muscle mass, quality, and function were impaired in patients with ESLD, whereas conventional assessments of muscle (L3 SMI and MAMC) highlighted no differences between ESLD and HC. Full evaluation of lower limb muscle health is essential in ESLD in order to accurately assess sarcopenia and target future interventions.

Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World.

The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological 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.

The Impact of Slice Interval and Equation on the Accuracy of Magnetic Resonance Image Estimation of Quadriceps Muscle Volume in End Stage Liver Disease.

Introduction: End stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is essential to evaluate sarcopenia in ESLD. However, manual segmentation of muscle volume (MV) can be laborious on cross-sectional imaging, due to the number of slices that require analysis. This study aimed to investigate the impact of reducing the number of slices required for MV estimation. Further, we aimed to compare two equations utilized in estimating MV (cylindrical and truncated cone). Methods: Thirty eight ESLD patients (23 males; 54.8 ± 10.7 years) were recruited from the Queen Elizabeth University Hospital Birmingham. A 3T MRI scan was completed of the lower limbs. Quadriceps MV was estimated utilizing 1-, 2-, 3-, and 4 cm slice intervals with both cylindrical and truncated cone equations. Absolute and relative error (compared to 1 cm slice interval) was generated for 2-, 3-, and 4 cm slice intervals. L3 skeletal muscle index (SMI) was also calculated in 30 patients. Results: Relative error increased with slice interval using the cylindrical (0.45 vs. 1.06 vs. 1.72%) and truncated cone equation (0.27 vs. 0.58 vs. 0.74%) for 2, 3, and 4 cm, respectively. Significantly, the cylindrical equation produced approximately twice the error compared to truncated cone, with 3 cm (0.58 vs. 1.06%, P < 0.01) and 4 cm intervals (0.74 vs. 1.72%, P < 0.001). Finally, quadriceps MV was significantly correlated to L3 SMI (r 2 = 0.44, P < 0.0001). Conclusion: The use of the truncated equation with a 4 cm slice interval on MRI offers an efficient but accurate estimation of quadricep muscle volume in ESLD patients.

The prevalence of frailty and pre-frailty among geriatric hospital inpatients and its association with economic prosperity and healthcare expenditure: A systematic review and meta-analysis of 467,779 geriatric hospital inpatients.

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.

The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.

Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.

Lack of significant seasonal association between serum 25(OH)D concentration, muscle mass and strength in postmenopausal women from the D-FINES longitudinal study.

The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006-2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups: <65 years (n=80) and ≥65 years (n=22). Outcome measures included lean mass (DXA), muscle strength (handgrip dynamometry) and serum 25(OH)D concentration (enzymeimmunoassay). Derived outcomes included appendicular skeletal muscle mass (ASM) and relative appendicular skeletal muscle index (RASM). Sarcopenia status was assessed using the European Working Group on Sarcopenia in Older People 2018 criteria. Non-parametric partial correlation using BMI as a covariate was used to evaluate the study aims. There were no statistically significant associations between total lean mass, ASM or RASM and 25(OH)D in any group at any season. There was a trend for handgrip strength to be positively associated with serum 25(OH)D concentration. There was a trend showing a higher prevalence of sarcopenia in women ≥65 years. Sarcopenia status appeared transient for five women. In conclusion, the present study found no significant association between vitamin D status and functional indicators of musculoskeletal health, which were additionally not affected by season.

Determining the Influence of Habitual Dietary Protein Intake on Physiological Muscle Parameters in Youth and Older Age.

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.

Overcoming protein-energy malnutrition in older adults in the residential care setting: A narrative review of causes and interventions.

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.

A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its Profile in Trauma: ADaPT.

INTRODUCTION: The 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. OBJECTIVE: Our 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 ANALYSIS: A 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 DISSEMINATION: This 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 REGISTRATION: This 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 PROGRESSION: The 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.

Factors associated with electrical stimulation-induced performance fatigability are dependent upon stimulation location.

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 < 0.001) and stimulated (NMES: -45 ± 12%, PNS -27 ± 27%, both P < 0.001) force reductions. Although distinct between protocols, myoelectrical indicators of muscle recruitment (M-wave area and amplitude) and nerve conduction time did not change throughout either protocol. Myoelectrical propagation speed, represented as M-wave duration, and the delay before muscle relaxation began both progressively increased during NMES only (P < 0.05 and P < 0.001, respectively). NMES myoelectrical changes suggested performance fatigability, indicating activation of superficial fibres only, which was not observed with PNS. This suggests PNS recruits a wider pool of muscle fibres and motor units and is a favourable alternative for rehabilitation. Future work should focus on implementing PNS interventions in clinically relevant scenarios such as immobilisation, care homes and critical illness.

Feasibility, Efficacy, and Safety of Percutaneous Muscle Biopsies in Patients With Chronic Liver Disease.

INTRODUCTION: Sarcopenia is present in many chronic disease states including decompensated end stage liver disease (ESLD) and non-cirrhotic non-alcoholic fatty liver disease (NAFLD). Sarcopenia in ESLD can negatively impact quality of life and increase mortality. Despite this, very little is understood about the mechanisms of sarcopenia in these conditions. One key reason for this is the reluctance to undertake percutaneous muscle biopsies due to the perceived increased risks. ESLD can induce thrombocytopaenia and coagulopathy which significantly increases the risk of bleeding. In addition, patients with either NAFLD or ESLD often have co-morbidities that would require additional care and risk assessment. Thus, the aim of this study was to establish an effective and safe protocol for the implementation of percutaneous muscle biopsies in patients with NAFLD and ESLD. METHODS: A total of 47 patients with ESLD and 9 patients with non-cirrhotic NAFLD were recruited from the Liver Unit, Queen Elizabeth Hospital (Birmingham, United Kingdom). A total of 71 percutaneous vastus lateralis biopsies were attempted over two study visits. A vigorous safety screening occurred prior to and during each visit and a strict protocol was followed to mitigate against complications and risk. RESULTS: A total of 85% of patients consented to the muscle biopsy at either visit (48/56). A total of 9% of consented biopsies could not occur due to medical considerations, including high international normalised ratio (INR) (n = 3) and the use of aspirin (n = 4). Muscle tissue was obtained from 90% of attempts, with a mean average yield (wet weight tissue) of 98.1 ± 52.9 mg. CONCLUSION: Percutaneous muscle biopsies are both feasible and yield sufficient tissue in an ESLD population. The procedure is effective for obtaining muscle tissue whilst also safe, with only one adverse event. This study provides evidence for the successful use of muscle biopsies in this population, even in consideration of disease specific complications, medications, and comorbidities.

Sarcopenia in chronic liver disease: mechanisms and countermeasures.

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.

The association between nutrient intake, nutritional status and physical function of community-dwelling ethnically diverse older adults.

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-h 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: Complete data were collected 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. Statistically significant 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 < 0.001) and nutritional status (Z = -2.37, p = 0.018) declined over time. Higher SPPB scores at baseline (OR = 0.54 95% CI 0.35, 0.81) were associated with a slower decline in nutritional status. CONCLUSION: The observed declines and inadequate nutrient intakes in the absence of weight loss in just 8 months may pose serious challenges to healthy ageing, identifying an urgent need to re-evaluate and tailor appropriate dietary advice for this population. Additionally, the associations of nutrition and physical function observed in this study serves as an essential resource to design and implement community/faith-based interventions targeting early screening of nutritional status and physical function to ensure most older adults are assessed and treated accordingly.

Protocol for understanding acute sarcopenia: a cohort study to characterise changes in muscle quantity and physical function in older adults following hospitalisation.

BACKGROUND: Older adults are vulnerable to the effects of acute sarcopenia (acute muscle insufficiency) following hospitalisation. However, this condition remains poorly characterised to date. It is hypothesised that acute sarcopenia arises due to a combination of bed rest and inflammatory surge. This study aims to characterise changes in muscle quantity and function, determining which factors (clinical and biological) are most predictive, and how these relate to change in physical function at 13 weeks. METHODS: This study will include three groups of patients aged 70 years and older; patients undergoing elective colorectal surgery, patients admitted for emergency abdominal surgery, and patients admitted under general medicine with acute bacterial infections. Changes in muscle quantity (Bilateral Anterior Thigh Thickness with ultrasound and bioelectrical impedance analysis) and muscle function (muscle strength, physical performance) within 1 week of hospitalisation or surgery will be characterised, with follow-up of patients at 13 weeks. Physical function will be measured using the Patient Reported Outcome Measures Information System, and the Short Physical Performance Battery (or gait speed alone within 1 week of surgery). DISCUSSION: This study will fully characterise changes in muscle quantity and function in hospitalised older adults and enable risk stratification towards targeted interventions in clinical practice. The results of this study will inform further research involving interventions to ameliorate changes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03858192 ; Prospectively registered 28th February 2019.

Social networks and their influences on nutrient intake, nutritional status and physical function in community-dwelling ethnically diverse older adults: a mixed-methods longitudinal study.

BACKGROUND: The United Kingdom population is ageing and becoming increasingly diverse; thus, it is vital to develop and implement interventions supporting this population shift. Social networks (SN) significantly impact health outcomes in later life, however relatively little is known about SN of community-dwelling ethnically diverse older adults. This study aimed to: 1) profile SN and changes in SN in this population over 8 months; 2) examine associations between SN, dietary intake, nutritional status, and physical function. METHODS: SN were assessed using the Wenger Practitioner Assessment of Network Type. Energy and nutrient intakes were measured using multiple-pass 24-h recalls. The Mini Nutritional Assessment-Short Form (MNA-SF) assessed nutritional status. Physical function was measured using the Short Physical Performance Battery (SPPB) and handgrip strength. Data were collected at baseline and 8-months. Correlation and regression analyses examined relationships between SN, physical function, nutrient intake and nutritional status. Semi-structured interviews were conducted at baseline (n = 92) and follow-up (n = 81) to identify potential influences of SN. Interviews were transcribed verbatim and analysed using directed content analysis. RESULTS: Quantitative data were obtained from 100 participants at baseline and 81 at follow-up. Mean (SD) age was 70.8 (8.1) years (59% male), comprising African/Caribbean (60%), South Asian (34%), and other ethnicities (6%). Five SN typologies were identified under two broad areas: integrated-SN consisting of locally integrated (44%) and wider community (8%); and non-integrated-SN consisting of family dependent (25%), local self-contained (17%), and private restricted (6%). At follow-up, 37% remained in non-integrated networks, 19% transitioned to non-integrated networks, 11% transitioned to, and 33% remained in, integrated networks. Participants within integrated networks at baseline had higher SPPB scores at follow-up. Compared to the private restricted, local self-contained SN significantly predicted zinc, riboflavin and vitamin B6 intakes. Participants remaining in, or transitioning to, non-integrated networks had low MNA-SF scores. Qualitative findings indicate that participants with reductions in SN perceived it as causing poorer physical function and eating behaviours. CONCLUSION: In the present study, integrated SN were associated with higher physical function and nutritional status at 8-month's follow-up. These results can inform the design of interventions to improve social networks, physical function and healthy nutrition within this population.

Physical Activity Intervention for Loneliness (PAIL) in community-dwelling older adults: a randomised feasibility study.

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.

Amount, Source and Pattern of Dietary Protein Intake Across the Adult Lifespan: A Cross-Sectional Study.

Objectives: Sub-optimal dietary protein consumption may partially underlie the age-related loss of muscle mass and function (sarcopenia). Specifically, dose, timing, source and distribution of dietary protein across the day might influence muscle anabolism in individuals from across the lifespan. Design: The present study aimed to assess daily and meal-specific protein intake, protein source and protein intake pattern in 40 young (23.8 ± 4.3 years), 40 middle-aged (51.6 ± 4.1 years), and 40 old (77.4 ± 7.4 years) individuals using 3-day weighed food diaries. Results: Old individuals consumed on average 83.4 ± 24.6 g of daily protein, which was significantly lower compared with young but not middle-aged individuals who consumed, respectively, 105.1 ± 43.0 g and 97.0 ± 31.1 g of daily protein (P = 0.013). No significant difference in daily protein intake was found with middle-aged individuals. Dietary protein intake pattern was uneven across meals for all groups (P < 0.001 for all). Sources of protein consumption were similar between groups except at lunch where old individuals ingested lower quality proteins compared with middle aged and young individuals. Conclusion: Although total daily protein intake was sufficient in the majority of participants, per-meal protein intake and protein distribution contend the current knowledge regarding optimal protein intakes. Increasing protein intake, especially at breakfast and lunch, could mitigate age-related muscle loss.

Influence of combined vitamin D3 supplementation and resistance exercise training on musculoskeletal health in older men and women (EXVITD): protocol for a randomised controlled trial.

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 numberNCT02467153; Post-results.