Harnish P. Patel

Prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) definition: findings from the Hertfordshire Cohort Study (HCS)

Introduction: sarcopenia is associated with adverse health outcomes. The aim of this study was to describe the prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus definition. Methods: we applied the EWGSOP definition to 103 community-dwelling men participating in the Hertfordshire Sarcopenia Study (HSS) using both the lowest third of dual-energy X-ray absorptiometry (DXA) lean mass (LM) and the lowest third of skin-fold-based fat-free mass (FFM) as markers of low muscle mass. We also used the FFM approach among 765 male and 1,022 female participants in the Hertfordshire Cohort Study (HCS). Body size, physical performance and self-reported health were compared in participants with and without sarcopenia. Results: the prevalence of sarcopenia in HSS men (mean age 73 years) was 6.8% and 7.8% when using the lowest third of DXA LM and FFM, respectively. DXA LM and FFM were highly correlated (0.91, P < 0.001). The prevalence of sarcopenia among the HCS men and women (mean age 67 years) was 4.6% and 7.9%, respectively. HSS and HCS participants with sarcopenia were shorter, weighed less and had worse physical performance. HCS men and women with sarcopenia had poorer self-reported general health and physical functioning scores. Conclusions: this is one of the first studies to describe the prevalence of sarcopenia in UK community-dwelling older people. The EWGSOP consensus definition was of practical use for sarcopenia case finding. The next step is to use this consensus definition in other ageing cohorts and among older people in a range of health-care settings.

New horizons in the pathogenesis, diagnosis and management of sarcopenia

Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. One of the most important recent developments has been convergence in the operational definition of sarcopenia combining measures of muscle mass and strength or physical performance. This has been accompanied by considerable progress in understanding of pathogenesis from animal models of sarcopenia. Well-described risk factors include age, gender and levels of physical activity and this knowledge is now being translated into effective management strategies including resistance exercise with recent interest in the additional role of nutritional intervention. Sarcopenia is currently a major focus for drug discovery and development although there remains debate about the best primary outcome measure for trials, and various promising avenues to date have proved unsatisfactory. The concept of ‘new tricks for old drugs’ is, however, promising, for example, there is some evidence that the angiotensin-converting enzyme inhibitors may improve physical performance. Future directions will include a deeper understanding of the molecular and cellular mechanisms of sarcopenia and the application of a lifecourse approach to understanding aetiology as well as to informing the optimal timing of interventions.

Understanding how we age: insights into inflammaging

Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory.Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production.Complex interrelated genetic, environmental and age-related factors determine an individual’s vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions.

The developmental origins of sarcopenia.

Sarcopenia is defined as the loss of skeletal muscle mass and strength with age1. There is increasing recognition of the serious health consequences of sarcopenia both in terms of disability2, morbidity3 and mortality4, and in terms of significant healthcare costs5. Adult determinants of sarcopenia including age, gender, size, levels of physical activity and heritability have been well described1;6-8. In particular the place of physical activity and resistance exercise training as the most effective intervention to slow loss is widely accepted9;10.

MUSCLE SIZE, STRENGTH AND PHYSICAL PERFORMANCE AND THEIR ASSOCIATIONS WITH BONE STRUCTURE IN THE HERTFORDSHIRE COHORT STUDY

Sarcopenia is associated with a greater fracture risk. This relationship was originally thought to be explained by an increased risk of falls in sarcopenic individuals. However, in addition, there is growing evidence of a functional muscle‐bone unit in which bone health may be directly influenced by muscle function. Because a definition of sarcopenia encompasses muscle size, strength, and physical performance, we investigated relationships for each of these with bone size, bone density, and bone strength to interrogate these hypotheses further in participants from the Hertfordshire Cohort Study. A total of 313 men and 318 women underwent baseline assessment of health and detailed anthropometric measurements. Muscle strength was measured by grip strength, and physical performance was determined by gait speed. Peripheral quantitative computed tomography (pQCT) examination of the calf and forearm was performed to assess muscle cross‐sectional area (mCSA) at the 66% level and bone structure (radius 4% and 66% levels; tibia 4% and 38% levels). Muscle size was positively associated with bone size (distal radius total bone area β = 17.5 mm2/SD [12.0, 22.9]) and strength (strength strain index (β = 23.3 mm3/SD [18.2, 28.4]) amongst women (p < 0.001). These associations were also seen in men and were maintained after adjustment for age, height, weight‐adjusted‐for‐height, limb‐length‐adjusted‐for‐height, social class, smoking status, alcohol consumption, calcium intake, physical activity, diabetes mellitus, and in women, years since menopause and estrogen replacement therapy. Although grip strength showed similar associations with bone size and strength in both sexes, these were substantially attenuated after similar adjustment. Consistent relationships between gait speed and bone structure were not seen. We conclude that although muscle size and grip strength are associated with bone size and strength, relationships between gait speed and bone structure and strength were not apparent in this cohort, supporting a role for the muscle‐bone unit.

Is grip strength a good marker of physical performance among community-dwelling older people?

IntroductionThere is increasing interest in physical performance as it relates to both the current and future health of older people. It is often characterised using the Short Physical Performance Battery including assessment of gait speed, chair rises and standing balance. However this battery of tests may not be feasible in all clinical settings and simpler measures may be required. As muscle strength is central to physical performance, we explored whether grip strength could be used as a marker of the Short Physical Performance Battery.ObjectiveTo examine associations between grip strength and components of the Short Physical Performance Battery in older community dwelling men and women.MethodsGrip strength measurement and the Short Physical Performance Battery were completed in 349 men and 280 women aged 63–73 years taking part in the Hertfordshire Cohort Study (HCS). Relationships between grip strength and physical performance (6m timed-up-and-go [TUG], 3m walk, chair rises and standing balance times) were analysed using linear and logistic regression, without and with adjustment for age, anthropometry, lifestyle factors and co-morbidities.ResultsAmong men, a kilo increase in grip strength was associated with a 0.07s (second) decrease in 6m TUG, a 0.02s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001 for all). Among women, a kilo increase in grip strength was associated with a 0.13s decrease in 6m TUG, a 0.03s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001). Higher grip strength was associated with better balance among men (p=0.01) but not women (p=0.57). Adjustment for age, anthropometry, lifestyle and co-morbidities did not alter these results.ConclusionsGrip strength is a good marker of physical performance in this age group and may be more feasible than completing a short physical performance battery in some clinical settings.

Hertfordshire sarcopenia study: design and methods

BackgroundSarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms.MethodsOne hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study.DiscussionThe novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

Increased expression of H19/miR-675 is associated with a low fat-free mass index in patients with COPD

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.

The developmental origins of sarcopenia: from epidemiological evidence to underlying mechanisms

Sarcopenia is defined as the loss of skeletal muscle mass and strength with age. There is increasing recognition of the serious health consequences in terms of disability, morbidity and mortality as well as major healthcare costs. Adult determinants of sarcopenia including age, gender, size, levels of physical activity and heritability have been well described. Nevertheless, there remains considerable unexplained variation in muscle mass and strength between older adults that may reflect not only the current rate of loss but the peak attained earlier in life. To date most epidemiological studies of sarcopenia have focused on factors modifying decline in later life; however, a life course approach to understanding sarcopenia, additionally, focuses on factors operating earlier in life including developmental influences. The epidemiological evidence linking low birth weight with lower muscle mass and strength is strong and consistent with replication in a number of different groups including children, young and older adults. However, most of the evidence for the cellular, hormonal, metabolic and molecular mechanisms underlying these associations comes from animal models. The next stage is to translate the understanding of mechanisms from animal muscle to human muscle enabling progress to be made not only in earlier identification of individuals at risk of sarcopenia but also in the development of beneficial interventions across the life course.

A feasibility study of implementing grip strength measurement into routine hospital practice (GRImP): study protocol

BackgroundHandgrip strength is a non-invasive marker of muscle strength, and low grip strength in hospital inpatients is associated with poor healthcare outcomes including longer length of stay, increased functional limitations, and mortality. Measuring grip strength is simple and inexpensive. However, grip strength measurement is not routinely used in clinical practice. The aim of this study is to evaluate the feasibility of implementing grip strength measurement into routine clinical practice.Methods/designThis feasibility study is a mixed methods design combining qualitative, quantitative, and economic elements and is based on the acute medical wards for older people in one hospital. The study consists of three phases: phase 1 will define current baseline practice for the identification of inpatients at high risk of poor healthcare outcomes, their nutrition, and mobility care through interviews and focus groups with staff as well as a review of patients’ clinical records. Phase 2 will focus on the feasibility of developing and implementing a training programme using Normalisation Process Theory to enable nursing and medical staff to measure and interpret grip strength values. Following the training, grip strength will be measured routinely for older patients as part of admission procedures with the use of a care plan for those with low grip strength. Finally, phase 3 will evaluate the acceptability of grip strength measurement, its adoption, coverage, and basic costs using interviews and focus groups with staff and patients, and re-examination of clinical records.DiscussionThe results of this study will inform the translation of grip strength measurement from a research tool into clinical practice to improve the identification of older inpatients at risk of poor healthcare outcomes.Trial registrationClinicaltrials.gov NCTO2447445