Reductions in Motor Unit Firing are Associated with Clinically Meaningful Leg Extensor Weakness in Older Adults.

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11-26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r's = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.

Comparison of strategies for assessment of rate of torque development in older and younger adults.

There is increasing appreciation of the role of rate of torque development (RTD) in physical function of older adults (OAs). This study compared various RTD strategies and electromyography (EMG) in the knee extensors and focused on discriminating groups with potential limitations in voluntary activation (VA) and associations of different RTD indices with functional tests that may be affected by VA in OAs. Neuromuscular function was assessed in 20 younger adults (YAs, 22.0 ± 1.7 years) and 50 OAs (74.4 ± 7.0 years). Isometric ballistic and peak torque during maximal voluntary contractions (pkTMVC), doublet stimulation and surface EMG were assessed and used to calculate VA during pkTMVC and RTD and rate of EMG rise during ballistic contractions. Select mobility tests (e.g., gait speed, 5× chair rise) were also assessed in the OAs. Voluntary RTD and RTD normalized to pkTMVC, doublet torque, and peak doublet RTD were compared. Rate of EMG rise and voluntary RTD normalized to pkTMVC did not differ between OAs and YAs, nor were they associated with functional test scores. Voluntary RTD indices normalized to stimulated torque parameters were significantly associated with VA (r = 0.319-0.459), and both indices were significantly lower in OAs vs YAs (all p < 0.020). These RTD indices showed significant association with the majority of mobility tests, but there was no clear advantage among them. Thus, voluntary RTD normalized to pkTMVC was ill-suited for use in OAs, while results suggests that voluntary RTD normalized to stimulated torque parameters may be useful for identifying central mechanisms of RTD impairment in OAs.Clinical trial registration number NCT02505529; date of registration 07/22/2015.

Acute inspiratory resistance training enhances endothelium-dependent dilation and retrograde shear rate in healthy young adults.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously.

Deep breathing exercise at work: Potential applications and impact.

Hypertension is a major contributor to cardiovascular disease and daily deep breathing exercise (DBE) is a promising intervention to reduce blood pressure and stress in adults. DBE is simple, time-efficient, and does not require specialized equipment, allowing participation in a wide variety of settings. The workplace is an ideal setting to implement DBE at the national level for several reasons, including a large proportion of waking hours spent in the workplace, high levels of sedentary time at work, prevalence of work-related stress, and regular breaks throughout the day potentially reducing worker error. While the degree of adherence to daily workplace DBE will be the responsibility of the individual, employers and managers can (and should) do much to remove barriers to participation. Specifically, this could include: implementing regular short breaks or classes to perform DBE throughout the day, covering subscription costs for smartphone applications that guide DBE, and creating incentive programs for continuing DBE participation. Implementing DBE in the workplace is a pragmatic approach to provide a low-cost blood pressure and stress reduction therapy to a substantial portion of the adult population in the US, at least 50% of whom have high blood pressure.

A short course of high-resistance, low-volume breathing exercise extends respiratory endurance and blunts cardiovascular responsiveness to constant load respiratory testing in healthy young adults.

Our objective was to evaluate the effects of 6-weeks high-resistance, low-volume inspiratory muscle strength training (IMST) on respiratory endurance, blood pressure (BP) and heart rate (HR) responsiveness to high respiratory workloads. Ten healthy young adults completed two constant-load resistive breathing tests to exhaustion (Tlim) (target pressure =65 % maximal inspiratory pressure [PImax]; duty cycle = 0.7; breathing frequency matched to eupnea) separated by 6-weeks high-resistance (75 % maximal inspiratory pressure, PImax), low-volume (30 inspiratory efforts/day, 5 days/week) IMST. Throughout resistive breathing trials we measured beat-to-beat changes in BP and HR, mouth pressure, inspiratory muscle work and perceived exertion. POST resistive breathing tests revealed significant gains in endurance (PRE: 362.0 ± 46.6 s vs. POST: 663.8 ± 110.3 s, p = 0.003) and increases in respiratory muscle work (PRE: -9445 ± 1562 mmHg.s vs. POST: -16648 ± 3761 mmHg.s, p = 0.069). Conversely, systolic and diastolic BP responses, HR and ratings of perceived exertion all declined. Consistent with previous observations, 6 weeks high resistance, low volume IMST lowered casual resting SBP (p = 0.002), DBP (p = 0.007) and mean arterial pressure (p = 0.001) and improved static inspiratory pressure. High resistance, low volume inspiratory muscle strength training extends respiratory endurance and attenuates BP responsiveness in healthy, recreationally-active young adults. The outcomes have implications for improved athletic performance and for attaining and/or maintaining cardiorespiratory fitness.

A multi-trial, retrospective analysis of the antihypertensive effects of high-resistance, low-volume inspiratory muscle strength training.

Above-normal blood pressure (BP) is a primary risk factor for cardiovascular diseases. In a retrospective analysis of five pilot trials, we assessed the BP-lowering effects of high-resistance inspiratory muscle strength training (IMST) in adults aged 18-82 years and the impact of IMST on maximal inspiratory pressure (PIMAX), a gauge of inspiratory muscle strength and independent disease risk factor. Participants were randomized to high-resistance IMST (75% PIMAX) or low-resistance sham (15% PIMAX) training (30 breaths/day, 5-7 days/wk, 6 wk). IMST (n = 67) reduced systolic BP (SBP) by 9 ± 6 mmHg (P < 0.01) and diastolic BP (DBP) by 4 ± 4 mmHg (P < 0.01). IMST-related reductions in SBP and DBP emerged by week 2 of training (-4 ± 8 mmHg and -3 ± 6 mmHg; P ≤ 0.01, respectively) and continued across the 6-wk intervention. SBP and DBP were unchanged with sham training (n = 61, all P > 0.05). Select subject characteristics slightly modified the impact of IMST on BP. Greater reductions in SBP were associated with older age (ß = -0.07 ± 0.03; P = 0.04) and greater reductions in DBP associated with medication-naïve BP (ß = -3 ± 1; P = 0.02) and higher initial DBP (ß = -0.12 ± 0.05; P = 0.04). PIMAX increased with high-resistance IMST and low-resistance sham training, with a greater increase from high-resistance IMST (+20 ± 17 vs. +6 ± 14 cmH2O; P < 0.01). Gains in PIMAX had a modest inverse relation with age (ß = -0.20 ± 0.09; P = 0.03) and baseline PIMAX (ß = -0.15 ± 0.07; P = 0.04) but not to reductions in SBP or DBP. These compiled findings from multiple independent trials provide the strongest evidence to date that high-resistance IMST evokes clinically significant reductions in SBP and DBP, and increases in PIMAX, in adult men and women.NEW & NOTEWORTHY In young-to-older adult men and women, 6 wk of high-resistance inspiratory muscle strength training lowers casual systolic and diastolic blood pressure by 9 mmHg and 4 mmHg, respectively, with initial reductions observed by week 2 of training. Given blood pressure outcomes with the intervention were only slightly altered by subject baseline characteristics (i.e., age, blood pressure medication, and health status), inspiratory muscle strength training is effective in lowering blood pressure in a broad range of adults.

Age of Peak Performance Differs by Functional Task in Mice Tracked Over 2 Years.

Mouse models are often used to validate novel interventions prior to human testing, although biological differences between mice and humans limit the translatability of outcomes. A common assumption in animal research is that maximal physical performance will be present at a young age, and that differences in task performance between young and old can be attributed to the aging process. However, this may not be true for all physical function tasks, and leaving out intermediate time points could drastically alter data interpretation. Here, we document age-related changes in forelimb and hindlimb grip strength, balance and coordination, and body composition in mice (n = 43) collected at multiple time points between 4 and 24 months of age. Maximal forelimb grip strength was recorded at 4 months of age, but maximal hindlimb grip strength was recorded at 15 months of age. Balance performance was stable from 4 to 15 months of age, declining significantly at 18 months. Both lean and fat mass peaked at 18 months before declining steadily. We conclude that the inclusion of intermediate time points is essential for the accurate evaluation of physical function status in mice, particularly in the context of translating intervention outcomes into strategies to be tested in humans.

Heterogeneity of the strength response to progressive resistance exercise training in older adults: Contributions of muscle contractility.

BACKGROUND: Older adults display wide individual variability (heterogeneity) in the effects of resistance exercise training on muscle strength. The mechanisms driving this heterogeneity are poorly understood. Understanding of these mechanisms could permit development of more targeted interventions and/or improved identification of individuals likely to respond to resistance training interventions. Thus, this study assessed potential physiological factors that may contribute to strength response heterogeneity in older adults: neural activation, muscle hypertrophy, and muscle contractility. METHODS: In 24 older adults (72.3 ± 6.8 years), we measured the following parameters before and after 12 weeks of progressive resistance exercise training: i) isometric leg extensor strength; ii) isokinetic (60°/sec) leg extensor strength; iii) voluntary (neural) activation by comparing voluntary and electrically-stimulated muscle forces (i.e., superimposed doublet technique); iv) muscle hypertrophy via dual-energy x-ray absorptiometry (DXA) estimates of regional lean tissue mass; and v) intrinsic contractility by electrically-elicited twitch and doublet torques. We examined associations between physiological factors (baseline values and relative change) and the relative change in isometric and isokinetic muscle strength. RESULTS: Notably, changes in quadriceps contractility were positively associated with the relative improvement in isokinetic (r = 0.37-0.46, p ≤ 0.05), but not isometric strength (r = 0.09-0.21). Change in voluntary activation did not exhibit a significant association with the relative improvements in either isometric or isokinetic strength (r = 0.35 and 0.33, respectively; p > 0.05). Additionally, change in thigh lean mass was not significantly associated with relative improvement in isometric or isokinetic strength (r = 0.09 and -0.02, respectively; p > 0.05). Somewhat surprising was the lack of association between exercise-induced changes in isometric and isokinetic strength (r = 0.07). CONCLUSIONS: The strength response to resistance exercise in older adults appears to be contraction-type dependent. Therefore, future investigations should consider obtaining multiple measures of muscle strength to ensure that strength adaptations are comprehensively assessed. Changes in lean mass did not explain the heterogeneity in strength response for either contraction type, and the data regarding the influence of voluntary activation was inconclusive. For isokinetic contraction, the strength response was moderately explained by between-subject variance in the resistance-exercise induced changes in muscle contractility.

Six Months of Inspiratory Muscle Training to Lower Blood Pressure and Improve Endothelial Function in Middle-Aged and Older Adults With Above-Normal Blood Pressure and Obstructive Sleep Apnea: Protocol for the CHART Clinical Trial.

Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance-due to poor sleep quality and nocturnal hypoxemia-and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA. Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50-80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living. Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).

Perspective: Pragmatic Exercise Recommendations for Older Adults: The Case for Emphasizing Resistance Training.

Optimal health benefits from exercise are achieved by meeting both aerobic and muscle strengthening guidelines, however, most older adults (OAs) do not exercise and the majority of those who do only perform one type of exercise. A pragmatic solution to this problem may be emphasizing a single exercise strategy that maximizes health benefits. The loss of muscle mass and strength at an accelerated rate are hallmarks of aging that, without intervention, eventually lead to physical disability and loss of independence. Additionally, OAs are at risk of developing several chronic diseases. As such, participating in activities that can maintain or increase muscle mass and strength, as well as decrease chronic disease risk, is essential for healthy aging. Unfortunately, there is a widely held belief that adaptations to aerobic and resistance exercise are independent of each other, requiring the participation of both types of exercise to achieve optimal health. However, we argue that this assertion is incorrect, and we discuss crossover adaptations of both aerobic and resistance exercise. Aerobic exercise can increase muscle mass and strength, though not consistently and may be limited to exercise that overloads a particular muscle group, such as stationary bicycling. In contrast, resistance exercise is effective at maintaining muscle health with increasing age, and also has significant effects on cardiovascular disease (CVD) risk factors, type 2 diabetes (T2D), cancer, and mortality. We posit that resistance exercise is the most effective standalone exercise strategy for improving overall health in OAs and should be emphasized in future guidelines.

Sex differences in body composition but not neuromuscular function following long-term, doxycycline-induced reduction in circulating levels of myostatin in mice.

Age-related declines in muscle function result from changes in muscle structure and contractile properties, as well as from neural adaptations. Blocking myostatin to drive muscle growth is one potential therapeutic approach. While the effects of myostatin depletion on muscle characteristics are well established, we have very little understanding of its effects on the neural system. Here we assess the effects of long-term, post-developmental myostatin reduction on electrophysiological motor unit characteristics and body composition in aging mice. We used male (N = 21) and female (N = 26) mice containing a tetracycline-inducible system to delete the myostatin gene in skeletal muscle. Starting at 12 months of age, half of the mice were administered doxycycline (tetracycline) through their chow for one year. During that time we measured food intake, body composition, and hindlimb electromyographic responses. Doxycycline-induced myostatin reduction had no effect on motor unit properties for either sex, though significant age-dependent declines in motor unit number occurred in all mice. However, treatment with doxycycline induced different changes in body composition between sexes. All female mice increased in total, lean and fat mass, but doxycycline-treated female mice experienced a significantly larger increase in lean mass than controls. All male mice also increased total and lean mass, but administration of doxycycline had no effect. Additionally, doxycycline-treated male mice maintained their fat mass at baseline levels, while the control group experienced a significant increase from baseline and compared to the doxycycline treated group. Our results show that long-term administration of doxycycline results in body composition adaptations that are distinctive between male and female mice, and that the effects of myostatin reduction are most pronounced during the first three months of treatment. We also report that age-related changes in motor unit number are not offset by reduced myostatin levels, despite increased lean mass exhibited by female mice.

Changes in DXA-derived lean mass and MRI-derived cross-sectional area of the thigh are modestly associated.

Dual-energy X-ray absorptiometry (DXA) derived measures of lean mass demonstrate strong associations with magnetic resonance imaging (MRI) derived measures of muscle volume (MV) in cross-sectional studies, however, few studies have compared changes in response to an intervention. The purpose of this study was to determine the accuracy of DXA at detecting changes in lean mass, using MRI-derived MV as a reference standard. 10 male and 16 female subjects (29.2 ± 9.5 years) underwent DXA and MRI scans before and after a 10-week resistance training intervention. DXA thigh lean mass was compared to MRI mid-thigh MV, and percent change in size was compared between MRI and DXA. There was a strong correlation between measures cross-sectionally (r = 0.89) in agreement with previous investigations. However, there was a modest correlation of percentage change over time between methods (r = 0.49). Bland-Altman plots revealed that the amount of random error increased as the magnitude of the change from baseline increased. DXA measures of change in lean mass were modestly associated with MRI measures of change in MV. While there are several advantages to using DXA for the measurement of lean mass, the inability to accurately detect changes over time calls into question its use in clinical trials.

A Randomized Clinical Trial Comparing Three Different Exercise Strategies for Optimizing Aerobic Capacity and Skeletal Muscle Performance in Older Adults: Protocol for the DART Study.

Background: Age-related declines in physical function lead to decreased independence and higher healthcare costs. Individuals who meet the endurance and resistance exercise recommendations can improve their physical function and overall fitness, even into their ninth decade. However, most older adults do not exercise regularly, and the majority of those who do only perform one type of exercise, and in doing so are not getting the benefits of endurance or resistance exercise. Herein we present the study protocol for a randomized clinical trial that will investigate the potential for high-intensity interval training (HIIT) to improve maximal oxygen consumption, muscular power, and muscle volume (primary outcomes), as well as body composition, 6-min walk distance, and muscular strength and endurance (secondary outcomes). Methods and Analysis: This is a single-site, single-blinded, randomized clinical trial. A minimum of 24 and maximum of 30 subjects aged 60-75 that are generally healthy but insufficiently active will be randomized. After completion of baseline assessments, participants will be randomized in a 1:1:1 ratio to participate in one of three 12-week exercise programs: stationary bicycle HIIT, stationary bicycle moderate-intensity continuous training (MICT), or resistance training. Repeat assessments will be taken immediately post intervention. Discussion: This study will examine the potential for stationary bicycle HIIT to result in both cardiorespiratory and muscular adaptations in older adults. The results will provide important insights into the effectiveness of interval training, and potentially support a shift from volume-driven to intensity-driven exercise strategies for older adults. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (registration number: NCT03978572, date of registration June 7, 2019).