Altered H19/miR‐675 expression in skeletal muscle is associated with low muscle mass in community‐dwelling older adults

Background: Despite increasing knowledge of the pathogenesis of muscle ageing, the molecular mechanisms are poorly understood. Based on an expression analysis of muscle biopsies from older Caucasian men, we undertook an in-depth analysis of the expression of the long non-coding RNA, H19, to identify molecular mechanisms that may contribute to the loss of muscle mass with age. Methods: We carried out transcriptome analysis of vastus lateralis muscle biopsies from 40 healthy Caucasian men aged 68–76 years from the Hertfordshire Sarcopenia Study (HSS) with respect to appendicular lean mass adjusted for height (ALMi). Validation and replication was carried out using qRT-PCR in 130 independent male and female participants aged 73–83 years recruited into an extension of the HSS (HSSe). DNA methylation was assessed using pyrosequencing. Results: Lower ALMi was associated with higher muscle H19 expression (r2 = 0.177, P < 0.001). The microRNAs, miR-675-5p/3p encoded by exon 1 of H19, were positively correlated with H19 expression (Pearson r = 0.192 and 0.182, respectively, P < 0.03), and miR-675-5p expression negatively associated with ALMi (r2 = 0.629, P = 0.005). The methylation of CpGs within the H19 imprinting control region (ICR) were negatively correlated with H19 expression (Pearson r = −0.211 to −0.245, P ≤ 0.05). Moreover, RNA and protein levels of SMAD1 and 5, targets of miR-675-3p, were negatively associated with miR-675-3p (r2 = 0.792 and 0.760, respectively) and miR-675-5p (r2 = 0.584 and 0.723, respectively) expression, and SMAD1 and 5 RNA levels positively associated with greater type II fibre size (r2 = 0.184 and 0.246, respectively, P < 0.05). Conclusions: Increased expression profiles of H19/miR-675-5p/3p and lower expression of the anabolic SMAD1/5 effectors of bone morphogenetic protein (BMP) signalling are associated with low muscle mass in older individuals

Risk factors for incident falls in older men and women:The English longitudinal study of ageing

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Musculoskeletal health and life-space mobility in older adults: findings from the Hertfordshire Cohort Study

This study explores the relationship between musculoskeletal conditions of ageing and life-space mobility (LSM) in 1110 community-dwelling older adults from the Hertfordshire Cohort Study. LSM is a novel measure which captures ability to mobilise within the home, locally and more widely. Among men, older age, care receipt, not driving a car, lower wellbeing, and reduced physical function were associated with lower LSM, while in women only driving status and physical function were associated with LSM. Osteoporosis, arthritis, and fractures had no significant associations with LSM in either gender. These findings provide support for sex-specificity in the determinants of LSM and inform novel approaches to improving mobility and health in older age.</p

Mortality, bone density and grip strength: lessons from the past and hope for the future?

Objectives: therapeutic advances in management of osteoporosis and sarcopenia have occurred at different rates over the last two decades; here we examined associations between grip strength and bone mineral density (BMD) with subsequent all-cause and cause-specific mortality in a UK community-dwelling cohort.Methods: data from 495 men and 414 women from the Hertfordshire Cohort Study were analysed. Grip strength was assessed by grip dynamometry; femoral neck BMD was ascertained using DXA; deaths were recorded from baseline (1998–2004) until 31st December 2018. Grip strength and BMD in relation to mortality outcomes (all-cause, cardiovascular-related, cancer-related, and mortality due to other causes) were examined using Cox regression with adjustment for age and sex.Results: mean (SD) baseline age of participants was 64.3 (2.5) and 65.9 (2.6) years in men and women respectively. Lower grip strength was associated with increased risk of all-cause mortality (hazard ratio (95% CI): 1.30 (1.06,1.58), p = 0.010) and cardiovascular-related mortality (1.75 (1.20,2.55), p = 0.004). In contrast, BMD was not associated with any of the mortality outcomes (p &gt; 0.1) for all associations.Conclusion: we report strong relationships between grip strength and mortality in comparison with BMD. We hypothesize that this may reflect better recognition and treatment of low BMD in this cohort

Hospital admissions and mortality over 20 years in community-dwelling older people: findings from the Hertfordshire Cohort Study

Background: demographic changes worldwide are leading to pressures on health services, with hospital admissions representing an important contributor. Here, we report admission types experienced by older people and examine baseline risk factors for subsequent admission/death, from the community-based Hertfordshire Cohort Study. Methods: 2997 participants (1418 women) completed a baseline questionnaire and clinic visit to characterize their health. Participants were followed up from baseline (1998–2004, aged 59–73 years) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Baseline characteristics in relation to the risk of admission/death during follow-up were examined using sex-stratified univariate logistic regression. Results: during follow-up, 36% of men and 26% of women died and 93% of men and 92% of women had at least one hospital admission; 6% of men and 7% of women had no admissions and were alive at end of follow-up. The most common types of admission during follow-up were cardiovascular (ever experienced: men 71%, women 68%) and respiratory (men 40%, women 34%). In both sexes, baseline risk factors that were associated (p &lt; 0.05) with admission/death during follow-up were older age, poorer SF-36 physical function, and poorer self-rated health. In men, manual social class and a history of smoking, and in women, higher BMI, not owning one’s home, and a minor trauma fracture since age 45, were also risk factors for admission/death. Conclusions: sociodemographic factors were related to increased risk of admission/death but a small proportion experienced no admissions during this period, suggesting that healthy ageing is achievable.</p

Is lifestyle change around retirement associated with better physical performance in older age?: insights from a longitudinal cohort

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

What impact does osteoarthritis have on ability to self-care and receipt of care in older adults? Findings from the Hertfordshire Cohort Study

Objectives: living independently remains the aim of older adults, but musculoskeletal conditions and frailty may hamper this. We examined relationships between osteoarthritis with ability to self-care and access to formal/informal care among community-dwelling older adults, comparing results to relationships between other musculoskeletal conditions of ageing (frailty, sarcopenia, osteoporosis) and these outcomes. Design: data from the Hertfordshire Cohort Study were used. Osteoarthritis (hand, hip or knee) was defined by clinical examination. Osteoporosis was assessed using dual-energy X-ray absorptiometry and medication use. Sarcopenia was assessed using EWSGOP2 criteria, frailty using Fried criteria. Ability to self-care and access to formal/informal care were self-reported.Results: 443 men and women aged approximately 75 years participated. Osteoarthritis was reported by 26.8% participants; 11.8% had low grip strength; 21.4% had osteoporosis; 8.6% had sarcopenia; 7.6% were identified as frail. Most participants (90.7%) reported no problems with self-care, but more than one-fifth (21.4%) reported having received formal or informal care at home in the previous year. Odds of reporting difficulties with self-care were significantly greater (p ​&lt; ​0.05) for participants with osteoarthritis and for those with frailty, but not for those with osteoporosis or sarcopenia. Odds of receiving care at home in the past year were significantly greater among participants with osteoarthritis and among those with frailty, but not among those with osteoporosis or sarcopenia. Conclusions: frailty and osteoarthritis were associated with both difficulties with self-care and receipt of care; osteoporosis and sarcopenia were not. These results highlight the contribution of clinical osteoarthritis to ability to live independently in later life, and the need to actively manage the condition in older adults