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Background The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure. Methods We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach’s alpha. Responsiveness (Cohen’s d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability. Results We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach’s alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25–100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p r = − 0.45; p r = 0.48; p r = 0.48; p Conclusions SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.

Objectives: The aim of this study was to characterize the descriptive epidemiology of insomnia in midlife and explore the relative importance of different occupational risk factors for insomnia among older workers.Methods: A questionnaire was mailed to all adults aged 50–64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past three months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated.Results: Analysis was based on 8067 respondents (5470 in paid work), 18.8% of whom reported insomnia. It was more common among women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent among the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticized). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work [population attributable fraction (PAF) 15–33%] than shift work and lack of autonomy or support (PAF 5–7%). It was strongly associated with seven measures of poorer self-assessed health.Conclusions: Employment policies aimed at tackling insomnia among older workers may benefit from focusing particularly on job–person fit, job security and relationships in the workplace.

Background: Sarcopenia, the loss of muscle mass and strength, is associated adversely with disability, morbidity and mortality. Epidemiological findings suggest influences operating across the life course may be important. Our aim was to ascertain the feasibility and acceptability of obtaining muscle tissue from healthy older people in order to ultimately identify cellular mechanisms underlying life course influences on sarcopenia. Methods: 105 men with documented birth weight consented to detailed assessment of muscle mass and strength, and a biopsy of the vastus lateralis using the Weil-Blakesley conchotome. Acceptability was ascertained by questionnaire and a 100mm pain Visual Analogue Scale (VAS). 100mm indicated severe pain. Results: Muscle biopsy was successfully carried out in 102 out of 105 participants, mean yield 107mg (range 20-290mg). There were no serious wound complications. Ninety-three participants completed feedback questionnaires. The median pain VAS score during the procedure was 7mm (Interquartile range [IQR] 1-34), 4mm (IQR 0-16) one day after the procedure and 1mm (IQR 0-4) 7 days after the procedure. 60 (65%) participants were back to their normal levels of activity one day after the procedure. 85 (91%) found this procedure acceptable and would have the procedure again. Conclusion: Muscle biopsy using a Weil-Blakesley conchotome is both feasible and acceptable in community dwelling older men participating in epidemiological research. The excellent yield of biopsy tissue will allow morphological and molecular studies of muscle to be integrated into an epidemiological study facilitating investigation of the mechanisms underpinning sarcopenia that could potentially be altered by life course influences. © 2010 Serdi and Springer Verlag France.

Relationships between birthweight and grip strength throughout the life course suggest that early influences on the growth and development of muscle are important for long-term muscle function. However, little is known about parental influences on children's grip strength. We have explored this in the Southampton Women's Survey, a prospective general population cohort study from before conception through childhood. Grip strength was measured using a Jamar handgrip dynamometer in the mother at 19 weeks' gestation and her partner, and in the child at age 4 years. Pre-pregnancy heights and weights were measured in the mothers; reported weights and measured heights were available for the fathers. Complete data on parents and children were available for 444 trios. In univariable analyses, both parents' grip strengths were significantly associated with that of the child (r = 0.17, P < 0.001 for mothers; r = 0.15, P = 0.002 for fathers). These correlations were similar to that between the grip strength of the mothers and the fathers (r = 0.17, P < 0.001). In the multivariable model, after adjustment for child's height and physical activity, the correlations with the child's grip strength were attenuated, being 0.10 (P = 0.02) and 0.11 (P = 0.01) for mothers' and fathers' grip strength respectively. The findings show that grip strength of each parent is associated with that of the child, indicating that heritable influences and the shared family environment influence the development of muscle strength. This contributes to our understanding of the role of heritable and environmental factors on early muscle growth and development, which are important for muscle function across the life course.

Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147)) or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.

OBJECTIVES: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships. DESIGN: Cross-sectional and retrospective cohort study. SETTING: Hertfordshire, United Kingdom. PARTICIPANTS: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom. MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer. RESULTS: Grip strength was positively associated with height and weight at birth and inversely related to age (all P

BACKGROUND: Several recessive Mendelian disorders are common in Europeans, including cystic fibrosis (CFTR), medium-chain-acyl-Co-A-dehydrogenase deficiency (ACADM), phenylketonuria (PAH) and alpha 1-antitrypsin deficiency (SERPINA1).METHODS: In a multicohort study of >19 000 older individuals, we investigated the relevant phenotypes in heterozygotes for these genes: lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC)) for CFTR and SERPINA1; cognitive measures for ACADM and PAH; and physical capability for ACADM, PAH and SERPINA1.RESULTS: Findings were mostly negative but lung function in SERPINA1 (protease inhibitor (PI) Z allele, rs28929474) showed enhanced FEV1 and FVC (0.13 z-score increase in FEV1 (p=1.7×10(-5)) and 0.16 z-score increase in FVC (p=5.2×10(-8))) in PI-MZ individuals. Height adjustment (a known, strong correlate of FEV1 and FVC) revealed strong positive height associations of the Z allele (1.50 cm increase in height (p=3.6×10(-10))).CONCLUSIONS: The PI-MZ rare (2%) SNP effect is nearly four times greater than the 'top' common height SNP in HMGA2. However, height only partially attenuates the SERPINA1-FEV1 or FVC association (around 50%) and vice versa. Height SNP variants have recently been shown to be positively selected collectively in North versus South Europeans, while the Z allele high frequency is localised to North Europe. Although PI-ZZ is clinically disadvantageous to lung function, PI-MZ increases both height and respiratory function; potentially a balanced polymorphism. Partial blockade of PI could conceivably form part of a future poly-therapeutic approach in very short children. The notion that elastase inhibition should benefit patients with chronic obstructive pulmonary disease may also merit re-evaluation. PI is already a therapeutic target: our findings invite a reconsideration of the optimum level in respiratory care and novel pathway potential for development of agents for the management of growth disorders.

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

© 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting DisordersBackground: Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men. Methods: We identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence. Results: Imprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR-675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR-675 represses regeneration. Conclusions: The data suggest that increased expression of miR-675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.