A silver bullet for ageing medicine?: clinical relevance of T-cell checkpoint receptors in normal human ageing

Immunosenescence describes dysregulation of the immune system with ageing manifested in both the innate and adaptive immunity, including changes in T-cell checkpoint signaling. Through complex and nuanced process, T-cells lose excitatory signaling pathways and upregulate their inhibitory signaling, leading to ineffective immune responses that contribute to the formation of the ageing phenotype. Here we expand on the expression, function, and clinical potential of targeting the T-cell checkpoint signaling in age and highlight interventions offering the most benefits to older adults’ health. Notably, modifications in vaccination such as with mTOR inhibitors show immediate clinical relevance and good tolerability. Other proposed treatments, including therapies with monoclonal antibodies fail to show clinical efficacy or tolerability needed for implementation at present. Although T-cell co-signaling fits a valuable niche for translational scientists to manage immunosenescence, future study would benefit from the inclusion of older adults with multiple long-term conditions and polypharmacy, ensuring better applicability to actual patients seen in clinical settings

The recent secular trend in grip strength among older adults: findings from the English Longitudinal Study of Ageing

Purpose: Weaker grip strength in older adults is associated with adverse health outcomes and is a key component of sarcopenia. The secular trend of grip strength is, therefore, relevant in the setting of ageing populations. A recent study suggested differences in this trend among countries in mainland Europe. We used data from the English Longitudinal Study of Ageing (ELSA) to investigate the recent secular trend of older English adults. Methods: We used data on participants aged 50–89 having their first measurement of grip strength in waves 2 (2002/2003), 4 (2008/2009) or 6 (2012/2013) of ELSA. Grip was measured using a Smedley dynamometer. We expressed grip values as Z-scores (number of standard deviations above the age and gender mean from normative data) for use in linear regression analyses examining the annual secular trend after adjustment for potential confounders. Results: We included a total of 11,476 participants from the three waves of ELSA. Grip strength declined across the three waves, with mean (SD) Z-scores of 0.01 (0.94), − 0.06 (0.97) and − 0.20 (0.98) in waves 2, 4 and 6, respectively. The annual Z-score decline after adjustments was 0.03 SDs (95% CI 0.02, 0.03) per year. Conclusion: We saw evidence of a recent slight decline in the grip strength of older English adults. Over the 9-year period of this study, the decline seen is equivalent to 65-year-olds’ mean strength declining to that previously seen in individuals at age 69. Further monitoring of secular trends in grip strength and investigation of possible causes are warranted

Methodological challenges in a study on falls in an older population of Cape Town, South Africa

Background: Falls are a major cause of disability, morbidity and mortality in older persons, but have been under researched in developing countries. .Objective: To describe challenges encountered in a community-based study on falls in a multi-ethnic population aged ≥65 years in a low-income setting.Methods: The study was conducted in four stages: A pilot study (n=105) to establish a sample size for the survey. An equipment validation study (n=118) to use for fall risk determination. A cross-sectional baseline (n=837) and a 12-month follow-up survey (n=632) to establish prevalence and risk factors for falls.Results: Prevalence rate of 26.4% (95% CI 23.5-29.5%) and risk factors for recurrent falls: previous falls, self-reported poor mobility and dizziness were established. Adaptations to the gold standard prospective fall research study design were employed: 1) to gain access to the study population in three selected suburbs, 2) to perform assessments in a non-standardised setting, 3) to address subjects’ poverty and low literacy levels, and high attrition of subjects and field workers.Conclusion: Studies on falls in the older population of low- to middle-income countries have methodological challenges. Adaptive strategies used in the Cape Town study and the research experience reported may be instructive for investigators planning similar studies in such settings.Keywords: Falls, older people, community-based research, low and middle income countries, methodology, study desig

Television viewing, walking speed, and grip strength in a prospective cohort study.

PURPOSE: Television (TV) watching is the most prevalent sedentary leisure time activity in the United Kingdom. We examined associations between TV viewing time, measured over 10 yr, and two objective measures of physical capability, usual walking speed (UWS) and grip strength. METHODS: Community-based participants (n = 8623; 48-92 yr old) enrolled in the European Prospective Investigation of Cancer-Norfolk study attended a third health examination (3HC, 2006-2011) for measurement of maximum grip strength (Smedley dynamometer) and UWS. TV viewing time was estimated using a validated questionnaire (n = 6086) administered during two periods (3HC, 2006-2007; 2HC, 1998-2000). Associations between physical capability and TV viewing time category (<2, 2 < 3, 3 < 4, and ≥4 h·d) at the 3HC, 2HC, and using an average of the two measures were explored. Sex-stratified analyses were adjusted for age, physical activity, anthropometry, wealth, comorbidity, smoking, and alcohol intake and combined if no sex-TV viewing time interactions were identified. RESULTS: Men and women who watched the least TV at the 2HC or 3HC walked at a faster usual pace than those who watched the most TV. There was no evidence of effect modification by sex (Pinteraction = 0.09), and in combined analyses, participants who watched for <2 h·d on average walked 4.29 cm·s (95% confidence interval, 2.56-6.03) faster than those who watched for ≥4 h·d, with evidence of a dose-response association (Ptrend < 0.001). However, no strong associations with grip strength were found. CONCLUSIONS: TV viewing time predicted UWS in older adults. More research is needed to inform public health policy and prospective associations between other measures of sedentariness, such as total sitting time or objectively measured sedentary time, and physical capability should be explored.VLK declares a Wellcome Trust clinical training fellowship [092077/Z/10/Z] and KW a British Heart Foundation intermediate basic science research fellowship [FS/12/58/29709]. For the remaining authors no conflicts of interest were declared. The EPIC-Norfolk study was supported by programme grants from the Medical Research Council [G9502233; G0401527] and Cancer Research UK [C864/A8257]. A grant from Research into Ageing [262] funded the 3HC clinic.This is the final published version. It first appeared at http://journals.lww.com/acsm-msse/pages/articleviewer.aspx?year=2015&issue=04000&article=00008&type=abstract

Effect of Angiotensin System Inhibitors on Physical Performance in Older People - A Systematic Review and Meta-Analysis

Objective: Preclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area. Design: Systematic review and meta-analysis. Setting and Participants: Randomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance. Methods: We searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software. Results: Eight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI –0.22 to 0.29); P =.77; I2 = 53%], strength outcomes [6 trials, SMD –0.02 (95% CI –0.18 to 0.14), P =.83, I2 = 21%] or the short physical performance battery [3 trials, SMD –0.04 (95% CI –0.19 to 0.11), P =.60, I2 = 0%]. No evidence of publication bias was evident on inspection of funnel plots. Conclusions and Implications: Existing evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people

Remote collection of physical performance measures for older people: a systematic review

Remotely collected physical performance measures could improve inclusion of under-served groups in clinical research as well as enabling continuation of research in pandemic conditions. It is unclear whether remote collection is feasible and acceptable to older patients, or whether results are comparable to face-to-face measures. We conducted a systematic review according to a prespecified protocol. We included studies with mean participant age ≥ 60 years, with no language restriction. Studies examining the gait speed, Short Physical Performance Battery, distance walk tests, grip strength, Tinetti score, Berg balance test, sit-to-stand test and timed up and go were included. Reports of feasibility, acceptability, correlation between remote and face-to-face assessments and absolute differences between remote and face-to-face assessments were sought. Data were synthesised using Synthesis Without Meta-analysis methodology; 30 analyses from 17 publications were included. Study size ranged from 10 to 300 participants, with a mean age ranging from 61 to >80 years. Studies included a broad range of participants and conditions. Most studies had a moderate or high risk of bias. Only two studies undertook assessment of acceptability or feasibility, reporting good results. Correlation between face-to-face and remote measures was variable across studies, with no measure showing consistently good correlation. Only nine studies examined the accuracy of remote measures; in six studies, accuracy was rated as good (<5% mean difference between face-to-face and remote measures). There is a lack of robust evidence that remote collection of physical performance measures is acceptable to patients, feasible or provides comparable results to face-to-face measures

Methodological challenges in a study on falls in an older population of Cape Town, South Africa.

Background: Falls are a major cause of disability, morbidity and mortality in older persons, but have been under researched in developing countries. . Objective: To describe challenges encountered in a community-based study on falls in a multi-ethnic population aged 6565 years in a low-income setting. Methods: The study was conducted in four stages: A pilot study (n=105) to establish a sample size for the survey. An equipment validation study (n=118) to use for fall risk determination. A cross-sectional baseline (n=837) and a 12-month follow-up survey (n=632) to establish prevalence and risk factors for falls. Results: Prevalence rate of 26.4% (95% CI 23.5-29.5%) and risk factors for recurrent falls: previous falls, self-reported poor mobility and dizziness were established. Adaptations to the gold standard prospective fall research study design were employed: 1) to gain access to the study population in three selected suburbs, 2) to perform assessments in a non-standardised setting, 3) to address subjects\u2019 poverty and low literacy levels, and high attrition of subjects and field workers. Conclusion: Studies on falls in the older population of low- to middle-income countries have methodological challenges. Adaptive strategies used in the Cape Town study and the research experience reported may be instructive for investigators planning similar studies in such settings

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

BACKGROUND: Handgrip 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/DESIGN: This 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. DISCUSSION: The 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 REGISTRATION: Clinicaltrials.gov NCTO2447445