United Kingdom

Background: Patients with single, large-scale mitochondrial DNA (mtDNA) deletions often present with mitochondrial myopathy for which no treatment is available. Exercise intervention induces beneficial effects in mitochondrial myopathy; however, we do not yet understand the mechanism for this. Aim of the project: This study investigates biochemical, genetic and molecular changes triggered by resistant exercise training to identify exercise modulators on a molecular level in mitochondrial myopathy patients. Material and methods: Pre- and post-exercise vastus lateralis biopsies were taken from a cohort of single, large-scale mtDNA deletion patients (n = 5) after 16 weeks of supervised high-intensity resistant exercise training. Biopsies were assessed for changes in oxidative phosphorylation, mtDNA deletion level, fibre type and size, and differentially expressed (DE) genes (Figure 1). Conclusions: Resistance exercise training was safe and effective for our cohort of single, large-scale mtDNA patients. After exercise: • mitochondrial mass increase correlates with aerobic capability, • complex IV OXPHOS defect ameliorates in all patients, • fibre type I undergo hypertrophy mechanism in 4 patients, • there is differential gene expression. Future investigations of DE genes on SKM tissue with IMC will allow us to characterize their function on a protein level and to highlight potential exercise modulator(s) in mitochondrial myopathy patients.

ISTRC 2021 - International Sarcopenia Translational Research Conference

The effects of resistant exercise training in mitochondrial myopathy patients

exercise benefits

mitochondrial myopathy

resistant exercise

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Welcome to the inaugural International Sarcopenia Translational Research Conference.  “Where Worlds Meet” – the event brings together a broad range of researchers and practitioners in a truly interdisciplinary forum, covering discovery science through to clinical practice.

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Background: Resistance exercise (RE) is increasingly acknowledged as a primary countermeasure to age related chronic disease and represents an effective strategy for counteracting age-associated declines in muscle strength and physical performance. However, as training induced adaptation is primarily driven by the physiological stress imposed (i.e. the internal training response), eliciting a consistent and standardised training dose is necessary to maximise the potential of RE. Method: Thirty community-dwelling - older adults (71.7 ± 3.6 years; 12 female) naïve to RE, performed 6 weeks of twice weekly, machine-based progressive RE involving a combination of upper- and lower-body exercises (leg press, leg curl, chest press, upright row). RE programming - Participants performed 2-3 sets of 8-10 repetitions for each exercise per session with intensity set at 70% of estimated 1RM in session 1. Load was increased when participants completed the prescribed number of repetitions in the final set while maintaining proper form in two consecutive workouts. Quantification of training response - Internal training response was quantified using ratings of perceived exertion (RPE). Following each RE session, participants provided an overall rating of perceived exertion (sRPE) and differential ratings of perceived exertion for upper-body muscle exertion (sRPE-U) and lower-body muscle exertion (sRPE-L) using the CR100 scale3 . External load was quantified as relative volume load (no. of sets x no. of reps x %1RM). Data were analysed using mixed linear models. Results: Twenty-nine participants completed the intervention with an overall attendance of 97%. Conclusions: RE induced a substantial internal training response. There was no systematic change, but large interindividual variability in response, across the duration of the intervention. These metrics should be validated against objective measures of RE response such as improved muscle function.

Quantifying the internal training response to resistance exercise in older adults: findings from the Milk Intervention Muscle AgeiNg (MIlkMAN) pilot study

Background: Sarcopenia (loss of muscle mass, strength and function with age) is associated with disability, mortality and significant healthcare costs • Previous studies have examined measures of muscle mass, strength and function in relation to adverse health outcomes • No studies have explored both levels and changes in these measures in relation to multiple health outcomes in a single cohort • We examined this among participants of the Health, Aging and Body Composition (Health ABC) Study. Methods: • Analyses were based on 1412 men and 1490 women (aged 70-79 years at baseline) from the Health ABC Study (USA) • Characteristics ascertained from baseline (Year 1) to Year 6 • Muscle function by gait speed • Muscle strength by grip dynamometry • Appendicular lean mass (ALM) from DXA • Exposures for gait speed, grip strength and ALM • Mean levels over Years 1 to 6 • Change in z-scores (age and sex-specific) from Years 1 to 6 using linear mixed models • Time-to-first-event Cox regression was used to examine exposures in relation to adverse health outcomes. All models accounted for age, sex and ethnicity; fully-adjusted models also accounted for socio-demographic, lifestyle and clinical characteristics. • 10-year follow-up of outcomes after Year 6 • Deaths (adjudicated) • Hospital admissions (self-reported and adjudicated) • Low trauma fractures (self-reported and adjudicated) • Falls (self-reported). Results: • Participant characteristics are presented in Table 1 • Sarcopenia components were greater among men • Deaths and hospital admissions were more common among men • Low trauma fractures and falls were more common among women • Predictors of adverse health outcomes (Figure 1) • Mortality: lower levels and greater declines in each component • Hospital admission: lower levels and greater declines in each component; p=0.06 for ALM level • Low trauma fracture: lower levels of each component and greater declines in gait speed • Falls: lower gait speed and grip strength and greater declines in gait speed and ALM. Conclusion: • Lower levels and greater declines in muscle mass, strength and function predicted adverse outcomes • Lower gait speed and grip strength were more strongly associated with outcomes than lower ALM • Lifecourse interventions to maximise peak levels in earlier life and to reduce declines in later life may reduce disease burden in this age group. 

Level and change in sarcopenia components predict adverse health outcomes: findings from the Health, Aging and Body Composition Study

Background: • Identifying low muscle strength is a key step in many operational definitions of sarcopenia including the one proposed by the European Working Group on Sarcopenia in Older People-2 (EWGSOP2). • Assessment of grip strength is commonly used to identify people with low muscle strength. • There are a number of sources of variation in the protocols commonly used to assess grip strength including the type of hand-held dynamometer used. • Studies have shown marked variation in the grip strength achieved by individuals when tested using different makes and models of dynamometer. • The implications of these measurement differences for the case-finding of low muscle strength are not fully understood. • We aimed to assess the impact of measurement differences between 4 different types of commonly-used hand-held dynamometers on the case-finding of low muscle strength. Methods: STUDY DESIGN Randomised, repeated measurements cross-over study. STUDY PARTICIPANTS 118 men and women aged 45-74y who had previously taken part in a market research study, resided in London or the South East of England and met eligibility criteria, attended an assessment at a research office in central London between October 2015 and January 2016. MEASUREMENTS Maximum grip strength (kg) (of 2 trials in each hand) was assessed using four different handheld dynamometers (shown in figure A) in a randomly allocated order. ANALYSIS EWGSOP2 recommended cut-points (<27kg for men; <16kg for women) were applied to estimate prevalence of low muscle strength for each device. Agreement between devices was assessed using kappa statistics. Results: • Mean differences in maximum grip strength of between 4 and 5kg were found when comparing the hydraulic/spring-gauge devices with the electronic devices (Lessof et al, Under review). • These differences were reflected in marked variations in prevalence estimates of low muscle strength by dynamometer type (see figure B) with a range of 3% to 22% for men and 3% to 15% for women. • Of the 13 men classified as having low muscle strength by at least 1 dynamometer, only 1 man (8%) was identified by all 4 dynamometers and 7 men (54%) were identified by just 1 dynamometer (see figure C). • Of the 15 women classified as having low muscle strength by at least 1 dynamometer, only 1 woman (7%) was identified by all 4 dynamometers and 10 women (67%) were identified by just 1 dynamometer (see figure C). • This poor agreement between devices was reflected in kappa statistics comparing pairs of devices which ranged from 0.13 to 0.55. Conclusions: • Case-finding of low muscle strength is influenced by the type of hand-held dynamometer used. • It is important to identify the sources of variation in the measurement of grip strength (which include dynamometer type, body position during testing etc.) and consider the implications of these for sarcopenia. • We need to fully standardise the assessment of each of the different components of commonly used operational definitions of sarcopenia. • Where standardisation cannot be achieved, methods to take account of sources of variation in measurement need to be identified. • Options for this may include the development of correction factors and the use of different reference values and cut-points for different measurement devices.

Impact of variation in device used to measure grip strength on the identification of low muscle strength: Findings from a randomised cross-over study

Background: • Identifying individuals with low grip strength is an initial step in many operational definitions of sarcopenia. • Evidence indicates that contemporaneous Russian populations may have lower mean levels of grip strength than other populations in northern Europe with important implications for sarcopenia. Methods: Study participants - Men and women aged 40-69y from the Russian Know Your Heart study (KYH) (n=3,833) and the seventh survey of the Norwegian Tromsø Study (n=5,598) with valid grip strength measures KYH – a cross-sectional survey of men and women residing in 2 Russian cities - Novosibirsk & Arkhangelsk – recruited from the general population using random sampling of addresses from regional health insurance databases conducted in 2015-2018 Tromsø Study – a longitudinal study of men and women residing in the municipality of Tromsø, Norway, seventh survey conducted in 2015-2016. Measurements - The same standardised protocols were used to assess grip strength in both studies. Grip strength was assessed by trained health professionals using Jamar+ Digital dynamometers following the Southampton protocol. Maximum grip strength (kg) (of 3 trials in each hand) was used in analyses. Analysis - Grip strength by age, sex and study was modeled using linear regression and between-study differences were predicted from these models. Results: • Mean grip strength was higher among Tromsø than KYH study participants and this difference did not vary markedly by age or sex (figure 1). • Adjustment for covariates, most notably height, attenuated between-study differences but these differences were still evident at younger ages (figure 2). • For example, estimated between-study differences in mean grip strength in fullyadjusted models were 2.2kg (95% CI 1.4, 3.1) at 40 years and 1.0kg (95% CI 0.5, 1.5) at 65 years in men (age x study interaction p=0.09) and 1.1kg (95% CI 0.4, 1.9) at age 40 years and -0.2kg (95% CI -0.7, 0.3) at 65 years in women (age x study interaction p<0.01). Conclusions: • We found between-study differences in mean grip strength at ages 40-69 years that are likely to translate into greater future risk of sarcopenia and poorer prospects of healthy ageing for Russian than Norwegian study participants. • For example, the average Russian participant had a similar level of grip strength to a Norwegian participant 7 years older. • Height has its origins in childhood. As this covariate had the most marked impact on between-study differences in grip strength this suggests that these differences may have their origins in early life. • This supports the need for life course approaches to the prevention of sarcopenia and promotion of healthy ageing.

Between-study differences in grip strength: a comparison of Norwegian and Russian adults aged 40-69 years

Introduction: One in three older adults fall yearly with 30-50% of falls resulting in injury. Falls are estimated to cost £2.3bn yearly in the UK. With an ageing population there is a growing need to be able to identify fallers in order to target fall prevention strategies. Methods: This was an observational cohort study of 4,239 participants (60-90 years) from Wave 6 and 7 of the English Longitudinal Study of Ageing. Low muscle strength (dynapenia) and obesity were defined using criteria below at Wave 6. Selfreported data on falls and fall-related injuries (2-year followup) were collected (Wave 7). Multiple logistic regression analyses were performed adjusting for age, sex and previous fall history. AUC was calculated from logistic models. Conclusion: Abdominal obesity and dynapenia appear to confer a greater risk of falls than either component alone. However, individual discrimination was low. The current challenge remains to find a way to operationalise a functionally relevant definition of dynapenic obesity at an individual level.

Dynapenic Abdominal Obesity as a risk factor for falls and fall-related injuries

Background: Weak grip strength is associated with a range of adverse health outcomes such as disability and mortality1 and an accelerated decline in grip strength confers an even greater health risk2 . Two important areas to consider are long-term conditions (LTCs), which can be used to identify individuals at increased risk of sarcopenia using routine health records, and lifestyle factors, which are potentially modifiable and targets for intervention. Methods: Participants We used data from UK Biobank participants who had grip strength measured at baseline (2006-10) and a subsequent study visit around nine years later. Ethical approval for UK Biobank was obtained from the North West Multi-Centre Research Ethics Committee. At baseline, participants’ LTCs were self-reported and categorised against a hierarchy. The number of LTC categories present was categorised as 0, 1, 2 and 3+ (with 2+ categories classed as multimorbidity). Lifestyle factors (body mass index (BMI), smoking, diet and physical activity) were assessed. Change in grip strength was grouped into four patterns: decline, stable low, stable high or reference (no change or increase)3 . Statistical analysis The sample was restricted to participants with complete data on LTCs, lifestyle factors and patterns of grip strength change. We used multinomial logistic regression to assess associations between exposures (categories of LTCs, multimorbidity and lifestyle factors) and outcome (pattern of grip strength change). Results: A total of 44,315 (51.1% female) participants at ages 40-70 were included in the final sample. The median time between visits was 9.2 (7.6, 10.3) years. In terms of patterns of grip strength change, 6.2% had stable low strength, 6.9% had stable high strength, 15.5% experienced a decline in strength and the remainder (71.4%) were in the reference pattern. Most categories of LTCs had significant independent associations with grip strength change (results not shown). There were graded associations between the degree of multimorbidity and pattern of grip strength change, independent of lifestyle factors. For example, those with three or more categories of LTCs were at increased risk of decline in grip strength, a marked increase in stable low grip strength and were less likely to experience stable high grip strength. All lifestyle factors had significant associations except frequent consumption of processed meat. Low physical activity was associated with adverse patterns of grip strength, while raised BMI had divergent associations (both the decline and stable high patterns of grip strength change). Conclusion: Individuals living with multimorbidity and those with lifestyle risk factors are at increased risk of low muscle strength and loss of strength over time. Our findings suggest potential target groups in mid-life for assessment of grip strength, leading to established interventions such as resistance exercise training and the identification of participants for future research studies.

Long-term conditions, multimorbidity, lifestyle factors and change in grip strength over 9 years of follow-up: findings from 44,315 UK Biobank participants

Methods: This report included Biobank participants recruited between 2006-2010 with COVID-19 test data. Cindex was used to examine predictive discrimination of individual Fried’s frailty components (slowness, weakness, low physical activity, exhaustion, weight loss) and overall status for two COVID-19 outcomes: 1) Mild disease: a positive COVID-19 test from a community setting without evidence of severe disease 2) Severe disease: a positive in-hospital COVID-19 test or COVID-19 as a primary cause of death defined as severe COVID-19. Results: • Out of 358,433 included in the main analysis, 9,679 patients were classified as having mild COVID-19 and 2,964 were classified as having severe COVID-19. • The prevalence of physical frailty was highest in the severe COVID-19 group (8.1%) compared to mild COVID-19 group (3.2%) and with no COVID-19 diagnosis (2.9%). • For severe COVID-19 outcomes, selfreported walking pace provided the greatest risk discrimination compared to other individual frailty indicators, or overall frailty status. Results for mild COVID-19 were similar, however C-index improvement were lower. Summary: A simple self-reported measure of walking pace provides the greatest predictive discrimination for severe COVID-19 outcomes compared to other frailty indicators or overall frailty status.

Physical frailty components and risk prediction of COVID-19 outcomes: UK Biobank analysis


Background and aim: • Muscle weakness is a key criterion for sarcopenia. A condition which is highly prevalent and likely to increase with time as populations age, with profound implications for individuals, their families and society. • Research suggests lower childhood socioeconomic position (SEP) contributes to muscle weakness in later life… • but there is little evidence in younger adults closer to peak muscle strength from more recently born cohorts. • We aimed to examine the relationships between indicators of SEP in childhood and adulthood and grip strength at age 46-years. Methods: The 1970 British Cohort Study (BCS70) is comprised of males and females born in England, Scotland, and Wales during a single week in 1970. A total of 3,113 men and 3,132 women from the BCS70 with data on paternal occupational class and parental education level at age 5 and own occupational class, education level, grip strength and covariates including height, body mass index and occupational activity at age 46, were included in analyses. Interactions between sex and each SEP indicator were formally assessed, and models sex-stratified if evidence of interaction was found. Linear regression models were used to test associations of childhood and adulthood SEP with maximum grip strength. Conclusion & next step: • Women: lower SEP in both childhood and adulthood was associated with weaker grip strength suggesting that strategies to reduce women’s exposure to socioeconomic adversity across life are likely to be beneficial for their peak grip strength. • Men: lower SEP in adulthood appears to be associated with stronger grip at age 46-years related to higher levels of occupational activity. As evidence from other studies suggests associations between SEP and grip strength reverse in later life, strategies may be needed to help men of lower SEP maintain this midlife advantage as they age and retire. • Next step: we will complete a full analysis with more covariates and imputed missing data. This includes examining whether associations vary by body size, health status and health behaviours in childhood and adulthood, and whether associations of different indicators of SEP with grip strength are independent of each other.

Associations between socioeconomic position across life and grip strength at age 46 years: findings from the 1970 British Cohort Study

Introduction: Disadvantaged socioeconomic position (SEP) is associated with adverse health outcomes but has not been extensively studied for the muscle disease sarcopenia. This study aimed to estimate the prevalence of probable sarcopenia in community-dwelling older adults overall, and according to SEP. Methods: Participants from Wave 6 of the English Longitudinal Study of Ageing (ELSA) aged 60 years and older, with measured hand grip strength (HGS) or chair rise test performance were included (n= 6,052). SEP was defined by educational attainment. Conclusion: Disadvantaged socioeconomic position was associated with increased likelihood of probable sarcopenia, along with knownfactors such as older age and low physical activity. Our findings highlight the importanceof including socioeconomic disadvantage inresearch, strategies and polices aimed at theprevention of sarcopenia in older populations.

Health and Socioeconomic determinants of Probable Sarcopenia - 
an analysis of the English Longitudinal Study of Ageing

Introduction:
This research explores dietitians’ determinants of
practice in delivering advice on physical activity in older
adults to prevent sarcopenia. Evidence suggests
additional benefits from combined nutrition and exercise
for the prevention of sarcopenia 3,4, however dietitians
are not often considered as providers of advice on
physical activity. Dietitians are in an ideal position to
maximise every opportunity to provide comprehensive,
holistic advice and ultimately reduce the amount of
professionals patients have to engage with 2,5,6,7,8.
Methodology:
Qualitative methodology was chosen to explore indepth attitudes, opinions and perspectives of
participants.
The epistemological approach isinterpretivism, which
believes we understand and interpret the world
through our experiences, including through our social,
cultural, moral, ideological and political understanding.
The ontological position is relativism which believes
that there are multiple socially constructed realities. 
Conclusion:
Physical activity interventions should be included for all
older adults at risk of sarcopenia as an early intervention
for prevention, therefore, dietitians should offer advice on
physical activity as part of the Making Every Contact Count
initiative as a minimum. Role merging and upskilling of
dietitians can improve patient care and optimise services in
line with the NHS Long Term Plan (2019).

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