Search

Introduction: Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85 years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants., Methods: We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores., Results: The first 80 participants (53.8 % female) covered the target ages, ranging from 48 to 84 years. They were regularly physically active, reported good physical function and had a prevalence of sarcopenia (including probable sarcopenia) of 11.3 % based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95 % CI: -1.64, 1.83) above that expected., Conclusions: The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment, and prevention of sarcopenia., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD)., Objectives: We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD., Methods: Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ 1/2 PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV., Results: Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ 1/2 PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0-89% of fibres with low porin). There was a small amount of Complex I (0.16-4.59%) and Complex IV (0-3.79%) deficiency., Conclusions: Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The loss of mitochondrial function and content have been implicated in sarcopenia although they have been little studied in the very old, the group in which sarcopenia is most common. In this pilot study, our aim was to determine if mitochondrial respiratory chain function and content are preserved among healthy 85-year-olds., Methods: We recruited 19 participants (11 female) through their general practitioner and assessed their medical history, functional status and self-reported physical activity. We identified sarcopenia using grip strength, Timed Up-and-Go and bioimpedance analysis. We assessed mitochondrial respiratory chain function using phosphorous magnetic resonance spectroscopy, estimating τ 1/2 PCr, the recovery half-time of phosphocreatine in the calf muscles following a bout of aerobic exercise. We performed a biopsy of the vastus lateralis muscle and assessed mitochondrial respiratory chain content by measuring levels of subunits of complex I and IV of the respiratory chain, expressed as Z-scores relative to that in young controls., Results: Participants had a median (IQR) of 2 (1,3) long-term conditions, reported regular aerobic physical activity, and one participant (5.3%) had sarcopenia. Sixteen participants completed the magnetic resonance protocol and the mean (SD) τ 1/2 PCr of 35.6 (11.3) seconds was in keeping with preserved mitochondrial function. Seven participants underwent muscle biopsy and the mean fibre Z-scores were -0.7 (0.7) and -0.2 (0.4) for complexes I and IV, respectively, suggesting preserved content of mitochondrial respiratory chain enzymes., Conclusion: Muscle mitochondrial respiratory chain function and content are preserved in a sample of active, well-functioning 85-year-olds, among whom sarcopenia was uncommon. The results from this study will help inform future work examining the association between muscle mitochondrial deficiency and sarcopenia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Poor performance in physical tests such as grip strength and walking speed is a risk factor for disability in old age, although whether such measures improve the discrimination of clinical prediction models when traditional clinical risk factors are already known is not clear. The prevalence of disability in mid-life is relatively low and hence screening in this age group may present an opportunity for early identification of those at increased future risk who may benefit most from preventative interventions., Methods: Data were drawn from two waves of the Medical Research Council National Survey of Health and Development. We examined whether several chronic conditions, poor health behaviours and lower scores on three measures of physical performance (grip strength, chair rise speed and standing balance time) at age 53 were associated with self-reported mobility and/or personal care disability at age 69. We used the area under the curve statistic (AUC) to assess model discrimination., Results: At age 69, 44% (826/1855) of participants reported mobility and/or personal care disability. Our final clinical prediction model included sex, knee osteoarthritis, taking 2+ medications, smoking, increased BMI and poor performance in all three physical tests, with an AUC of 0.740 compared with 0.708 for a model which did not include the performance measures., Conclusion: Measures of physical performance in midlife improve discrimination in clinical prediction models for disability over 16 years. Importantly, these and similar measures are also potential targets of future diet, exercise and pharmacological intervention in mid-life., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72-81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p<0.01), cortical thickness (p<0.05) and trabecular number (p<0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p<0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory., Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression., Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error., Conclusions: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required., (Copyright © 2013. Published by Elsevier Inc.)

The FRAX(tr) algorithm uses clinical risk factors (CRF) and bone mineral density (BMD) to predict fracture risk but does not include falls history in the calculation. Using results from the Hertfordshire Cohort Study, we examined the relative contributions of CRFs, BMD and falls history to fracture prediction. We studied 2299 participants at a baseline clinic that included completion of a health questionnaire and anthropometric data. A mean of 5.5years later (range 2.9-8.8years) subjects completed a postal questionnaire detailing fall and fracture history. In a subset of 368 men and 407 women, bone densitometry was performed using a Hologic QDR 4500 instrument. There was a significantly increased risk of fracture in men and women with a previous fracture. A one standard deviation drop in femoral neck BMD was associated with a hazards ratio (HR) of incident fracture (adjusted for CRFs) of 1.92 (1.04-3.54) and 1.77 (1.16-2.71) in men and women respectively. A history of any fall since the age of 45years resulted in an unadjusted HR of fracture of 7.31 (3.78-14.14) and 8.56 (4.85-15.13) in men and women respectively. In a ROC curve analysis, the predictive capacity progressively increased as BMD and previous falls were added into an initial model using CRFs alone. Falls history is a further independent risk factor for fracture. Falls risk should be taken into consideration when assessing whether or not to commence medication for osteoporosis and should also alert the physician to the opportunity to target falls risk directly., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability., Methods: As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90+ years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance., Results: Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p=0.05, n=11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures., Conclusion: Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength. We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500). Birthweight and conditional weight at 1 year were strongly related to radial and tibial length in both sexes (p<0.001) and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use, and menopausal status in women. Among men, BMI was strongly positively associated with radial (r=0.46, p=0.001) and tibial (r=0.24, p=0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p=0.0002; tibia: p=0.08) and trabecular BMD (radius: p=0.08; tibia: p=0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p=0.0002; tibia: p=0.001) and trabecular (radius: p=0.008; tibia: p=0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p=0.006; fracture load X: p=0.005; fracture load Y: p=0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p=0.0001), cortical (p<0.005) and trabecular (p=0.0002) BMD, poorer forearm bone strength [polar SSI (p=0.006), fracture load X and Y (p=0.02)], and lower tibial total (p<0.001), cortical (p=0.008), and trabecular (p=0.0001) BMD. We have shown that growth in early life is associated with bone size and strength in a UK population aged 65-73 years. Lifestyle factors were associated with volumetric bone density in this population.