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Intense exercise training with insufficient recovery time is associated with reductions in neuromuscular performance. However, it is unclear how single muscle fibre mechanical function and myofibrillar Ca 2+ sensitivity contribute to these impairments. We investigated the effects of overload training on joint-level neuromuscular performance and cellular-level mechanical function. Fourteen athletes (4 female and 10 male) underwent a 3-week intensified training protocol consisting of up to 150% of their regular training hours with three additional high-intensity training sessions per week. Neuromuscular performance of the knee extensors was assessed via maximal voluntary contraction (MVC) force, electrically evoked twitch contractions, and a force-frequency relationship. Muscle biopsies were taken from the vastus lateralis to assess single fibre mechanical function. Neither MVC force nor twitch parameters were altered following training (all p > 0.05 ), but a rightward shift in the force-frequency curve was observed with average reduction in force of 6%-27% across frequencies 5-20 Hz (all p <  0.05). In single fibres, maximal force output was not reduced following training, but there was a rightward shift in the force-pCa curve driven by a 6% reduction in Ca 2+ sensitivity ( p < 0.05 ). These data indicate intensified training leads to impaired Ca 2+ sensitivity at the single fibre level, which in part explains impaired neuromuscular function at the joint level during lower frequencies of activation. This is an important consideration for athletes, as performance is often assessed at maximal levels of activation, and these underlying impairments in force generation may be less obvious., Competing Interests: No conflicts of interest, financial or otherwise, are declared by the authors.

Background: Residual force enhancement (rFE), defined as increased isometric force following active lengthening compared to a fixed-end isometric contraction at the same muscle length and level of activation, is present across all scales of muscle. While rFE is always present at the cellular level, often rFE "non-responders" are observed during joint-level voluntary contractions., Methods: We compared rFE between the joint level and single fiber level (vastus lateralis biopsies) in 16 young males. In vivo voluntary knee-extensor rFE was measured by comparing steady-state isometric torque between a stretch-hold (maximal activation at 150°, stretch to 70°, hold) and a fixed-end isometric contraction, with ultrasonographic recording of vastus lateralis fascicle length (FL). Fixed-end contractions were performed at 67.5°, 70.0°, 72.5°, and 75.0°; the joint angle that most closely matched FL of the stretch-hold contraction's isometric steady-state was used to calculate rFE. The starting and ending FLs of the stretch-hold contraction were expressed as % optimal FL, determined via torque-angle relationship., Results: In single fiber experiments, the starting and ending fiber lengths were matched relative to optimal length determined from in vivo testing, yielding an average sarcomere excursion of ∼2.2-3.4µm. There was a greater magnitude of rFE at the single fiber (∼20%) than joint level (∼5%) (p = 0.004), with "non-responders" only observed at the joint level., Conclusion: By comparing rFE across scales within the same participants, we show the development of the rFE non-responder phenomenon is upstream of rFE's cellular mechanisms, with rFE only lost rather than gained when scaling from single fibers to the joint level., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Production and hosting by Elsevier B.V.)

The age-related loss of muscle mass is partly accounted for by the loss of sarcomeres in series, contributing to declines in muscle mechanical performance. Resistance training biased to eccentric contractions increases serial sarcomere number (SSN) in young muscle, however, maximal eccentric training in old rats previously did not alter SSN and worsened performance. A submaximal eccentric training stimulus may be more conducive to adaptation for aged muscle. The purpose of this study was to assess whether submaximal eccentric training can increase SSN and improve mechanical function in old rats. Twelve 32-month-old male F344/BN rats completed 4 weeks of submaximal (60% maximum) eccentric plantar-flexion training 3 days/week. Pre- and post-training, we assessed in-vivo maximum isometric torque at a stretched and neutral ankle angle, the passive torque-angle relationship, and the isotonic torque-velocity-power relationship. The soleus and medial gastrocnemius (MG) were harvested for SSN measurements via laser diffraction, with the untrained leg as a control. SSN increased 11% and 8% in the soleus and MG, respectively. Training also shifted optimal torque production towards longer muscle lengths, reduced passive torque 42%, and increased peak isotonic power 23%. Submaximal eccentric training was beneficial for aged muscle adaptations, increasing SSN, reducing muscle passive tension, and improving dynamic contractile performance., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Exercise training is recommended to improve the quality of life in those living with Parkinson's disease (PD); however, the optimal prescription to improve cardiorespiratory fitness and disease-related motor symptoms remains unknown. Twenty-nine participants with PD were randomly allocated to either 10 wk of high-intensity interval training (HIIT) ( n = 15; 6 female) or moderate-intensity continuous training (MICT) ( n = 14; 5 female). The primary outcome was the change in maximal oxygen consumption (V̇o 2peak ). Secondary outcomes included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score, Parkinson's Fatigue Scale (PFS)-16, resting and exercise cardiovascular measures, gait, balance, and knee extensor strength and fatigability. Exercise training increased V̇o 2peak (main effect of time, P < 0.01), with a clinically meaningful difference in the change following HIIT versus MICT (Δ3.7 ± 3.7 vs. 1.7 ± 3.2 mL·kg -1 ·min -1 , P = 0.099). The UPDRS motor score improved over time ( P < 0.001) but without any differences between HIIT versus MICT (Δ-9.7 ± 1.3 vs. -8.4 ± 1.4, P = 0.51). Self-reported subjective fatigue (PFS-16) decreased over time ( P < 0.01) but was similar between HIIT and MICT groups ( P = 0.6). Gait, balance, blood pressure (BP), and heart rate (HR) were unchanged with training (all P > 0.09). Knee extensor strength increased over time ( P = 0.03) but did not differ between HIIT versus MICT (Δ8.2 ± 5.9 vs. 11.7 ± 6.2 Nm, P = 0.69). HIIT alone increased the muscular endurance of the knee extensors during an isotonic fatigue task to failure ( P = 0.04). In participants with PD, HIIT and MICT both increased V̇o 2peak and led to improvements in motor symptoms and perceived fatigue; HIIT may offer the potential for larger changes in V̇o 2peak and reduced knee extensor fatigability. NEW & NOTEWORTHY The optimal exercise prescription to improve cardiorespiratory fitness and disease-related motor symptoms in adults with Parkinson's disease remains unknown. In a single-center randomized trial consisting of either 10 wk of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), we found that both training modes increased V̇o 2peak , with a larger clinically meaningful difference following HIIT. Both exercise modes improved motor symptoms and subjective fatigue, whereas HIIT increased the muscular endurance of the knee extensors.

Background: Older adults exhibit a slower recovery of muscle mass following disuse atrophy than young adults. At a smaller scale, muscle fibre cross-sectional area (i.e., sarcomeres in parallel) exhibits this same pattern. Less is known, however, about age-related differences in the recovery of muscle fibre length, driven by increases in serial sarcomere number (SSN), following disuse. The purpose of this study was to investigate age-related differences in SSN adaptations and muscle mechanical function during and following muscle immobilization. We hypothesized that older adult rats would experience a similar magnitude of SSN loss during immobilization, however, take longer to recover SSN than young following cast removal, which would limit the recovery of muscle mechanical function., Methods: We casted the plantar flexors of young (8 months) and old (32 months) male rats in a shortened position for 2 weeks, and assessed recovery during 4 weeks of voluntary ambulation. Following sacrifice, legs were fixed in formalin for measurement of soleus SSN and physiological cross-sectional area (PCSA) with the un-casted soleus acting as a control. Ultrasonographic measurements of pennation angle (PA) and muscle thickness (MT) were conducted weekly. In-vivo active and passive torque-angle relationships were constructed pre-cast, post-cast, and following 4 weeks of recovery., Results: From pre- to post-cast, young and older adult rats experienced similar decreases in SSN (-20%, P < 0.001), muscle wet weight (-25%, P < 0.001), MT (-30%), PA (-15%, P < 0.001), and maximum isometric torque (-40%, P < 0.001), but there was a greater increase in passive torque in older (+ 180%, P < 0.001) compared to young adult rats (+ 68%, P = 0.006). Following cast removal, young exhibited quicker recovery of SSN and MT than old, but SSN recovered sooner than PA and MT in both young and old. PCSA nearly recovered and active torque fully recovered in young adult rats, whereas in older adult rats these remained unrecovered at ∼ 75%., Conclusions: This study showed that older adult rats retain a better ability to recover longitudinal compared to parallel muscle morphology following cast removal, making SSN a highly adaptable target for improving muscle function in elderly populations early on during rehabilitation., (© 2024. The Author(s).)

Introduction: We aimed to investigate the neuromuscular contributions to enhanced fatigue resistance with carbohydrate (CHO) ingestion and to identify whether fatigue is associated with changes in interstitial glucose levels assessed using a continuous glucose monitor (CGM)., Methods: Twelve healthy participants (six males, six females) performed isokinetic single-leg knee extensions (90°·s -1 ) at 20% of the maximal voluntary contraction (MVC) torque until MVC torque reached 60% of its initial value (i.e., task failure). Central and peripheral fatigue were evaluated every 15 min during the fatigue task using the interpolated twitch technique and electrically evoked torque. Using a single-blinded crossover design, participants ingested CHO (85 g sucrose per hour), or a placebo (PLA), at regular intervals during the fatigue task. Minute-by-minute interstitial glucose levels measured via CGM and whole blood glucose readings were obtained intermittently during the fatiguing task., Results: CHO ingestion increased time to task failure over PLA (113 ± 69 vs 81 ± 49 min, mean ± SD; P < 0.001) and was associated with higher glycemia as measured by CGM (106 ± 18 vs 88 ± 10 mg·dL -1 , P < 0.001) and whole blood glucose sampling (104 ± 17 vs 89 ± 10 mg·dL -1 , P < 0.001). When assessing the values in the CHO condition at a similar time point to those at task failure in the PLA condition (i.e., ~81 min), MVC torque, percentage voluntary activation, and 10 Hz torque were all better preserved in the CHO versus PLA condition ( P < 0.05)., Conclusions: Exogenous CHO intake mitigates neuromuscular fatigue at both the central and peripheral levels by raising glucose concentrations rather than by preventing hypoglycemia., (Copyright © 2024 by the American College of Sports Medicine.)

Aging is associated with impaired strength and power during isometric and shortening contractions, however, during lengthening (i.e., eccentric) contractions, strength is maintained. During daily movements, muscles undergo stretch-shortening cycles (SSCs). It is unclear whether the age-related maintenance of eccentric strength offsets age-related impairments in power generation during SSCs owing to the utilization of elastic energy or other cross-bridge based mechanisms. Here we investigated how aging influences SSC performance at the single muscle fibre level and whether performing active lengthening prior to shortening protects against age-related impairments in power generation. Single muscle fibres from the psoas major of young (∼8 months; n = 31 fibres) and old (∼32 months; n = 41 fibres) male F344BN rats were dissected and chemically permeabilized. Fibres were mounted between a force transducer and length controller and maximally activated (pCa 4.5). For SSCs, fibres were lengthened from average sarcomere lengths of 2.5 to 3.0 μm and immediately shortened back to 2.5 μm at both fast and slow (0.15 and 0.60 Lo/s) lengthening and shortening speeds. The magnitude of the SSC effect was calculated by comparing work and power during shortening to an active shortening contraction not preceded by active lengthening. Absolute isometric force was ∼37 % lower in old compared to young rat single muscle fibres, however, when normalized to cross-sectional area (CSA), there was no longer a significant difference in isometric force between age groups, meanwhile there was an ∼50 % reduction in absolute power in old as compared with young. We demonstrated that SSCs significantly increased power production (75-110 %) in both young and old fibres when shortening occurred at a fast speed and provided protection against power-loss with aging. Therefore, in older adults during everyday movements, power is likely 'protected' in part due to the stretch-shortening cycle as compared with isolated shortening contractions., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the effect of an unsupervised, body mass- home-based resistance training program in older adults performed at either a fast or slow contractile speed on changes to muscle-power, -volume, -architecture, and fatigue resistance of the knee extensors., Methods: Thirty-two male older adults (age 65-88 years) were separated into 1) fast-speed exercise (Fast-group), 2) slow-speed exercise (Slow-group), and 3) no exercise (Control-group) groups. Participants in the exercise groups performed 30-45 repetitions of knee-extension and sit-to-stand exercises 3 times a week for 8 weeks with different exercise speed between the groups. Before and after the intervention period, the following variables were measured: Isotonic power, isometric strength, twitch contractile properties, muscle-activity, -architecture, and -quality, neuromuscular fatigue resistance of the knee extensors, and thigh muscle volume., Results: Peak power was increased in both the Fast-group (+24 %, P < 0.01, d = 0.65) and Slow-group (+12 %, P < 0.05, d = 0.33) but not in the Control-group. Training increased pennation angle of the vastus lateralis in both the Fast-group (+8 %, P < 0.01, d = 0.42) and Slow-group (+8 %, P < 0.01, d = 0.42), while only the Fast-group showed increase in pennation angle of the rectus femoris (+12 %, P < 0.01, d = 0.64) and thigh muscle volume (+16 %, P < 0.01, d = 0.52). There was no time × group interaction effect for the other neuromuscular measures., Conclusions: Unsupervised, body mass- and home-based resistance training performed at either fast or slow speeds can improve muscle power in older adults, while fast-speed exercise may be preferable over slow-speed owing to the relatively greater improvement of muscle-power, -volume, -architecture, and better time efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

During aging, muscles undergo atrophy, which is partly accounted for by a loss of sarcomeres in series. Serial sarcomere number (SSN) is associated with aspects of muscle mechanical function including the force-length and force-velocity-power relationships; hence, the age-related loss of SSN contributes to declining performance. Training emphasizing eccentric contractions increases SSN in young healthy rodents; however, the ability for eccentric training to increase SSN in old age is unknown. Ten young (8 mo) and 11 old (32 mo) male Fisher344/BN rats completed 4 wk of unilateral eccentric plantar flexion training. Pre- and posttraining, the plantar flexors were assessed for the torque-frequency, passive torque-angle, and torque-velocity-power relationships. The soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were harvested for SSN assessment via laser diffraction, with the untrained leg used as a control. In the untrained leg/pretraining, old rats had lower SSN in the soleus, LG, and MG, lower maximum torque, power, and shortening velocity, and greater passive torque than young. Young showed increased soleus and MG SSN following training. In contrast, old had no change in soleus SSN and experienced SSN loss in the LG. Pre- to posttraining, young experienced an increase in maximum isometric torque, whereas old had reductions in maximum torque, shortening velocity, and power, and increased passive torque. Our results show that although young muscle has the ability to add sarcomeres in response to maximal eccentric training, this stimulus could be not only ineffective, but also detrimental to aged muscle leading to dysfunctional remodeling. NEW & NOTEWORTHY The loss of sarcomeres in series with age contributes to declining muscle performance. The present study investigated whether eccentric training could improve performance via serial sarcomere addition in old muscle, like in young muscle. Four weeks of maximal eccentric training induced serial sarcomere addition in the young rat plantar flexors and improved in vivo performance, however, led to dysfunctional remodeling accompanied by further impaired performance in old rats.

At a given exercise intensity, blood flow restriction (BFR) reduces the volume of exercise required to impair post-exercise neuromuscular function. Compared to traditional exercise, the time course of recovery is less clear. After strenuous exercise, force output assessed with electrical muscle stimulation is impaired to a greater extent at low versus high stimulation frequencies, a condition known as prolonged low-frequency force depression (PLFFD). It is unclear if BFR increases PLFFD after exercise. This study tested if BFR during exercise increases PLFFD and slows recovery of neuromuscular function compared to regular exercise. Fifteen physically active participants performed six low-load sets of knee-extensions across four conditions: resistance exercise to task failure (RE TF ), resistance exercise to task failure with BFR applied continuously (BFR CONT ) or intermittently (BFR INT ), and resistance exercise matched to the lowest exercise volume condition (RE VM ). Maximal voluntary contraction (MVC) force output, voluntary activation and a force-frequency (1-100 Hz) curve were measured before and 0, 1, 2, 3, 4 and 24 h after exercise. Exercise to task failure caused similar reductions at 0 h for voluntary activation (RE TF  = 81.0 ± 14.2%, BFR INT  = 80.9 ± 12.4% and BFR CONT  = 78.6 ± 10.7%) and MVC force output (RE TF  = 482 ± 168 N, BFR INT  = 432 ± 174 N, and BFR CONT  = 443 ± 196 N), which recovered to baseline values between 4 and 24 h. PLFFD occurred only after RE TF at 1 h supported by a higher frequency to evoke 50% of the force production at 100 Hz (1 h: 17.5 ± 4.4 vs. baseline: 15 ± 4.1 Hz, P = 0.0023), BFR INT (15.5 ± 4.0 Hz; P = 0.03), and RE VM (14.9 ± 3.1 Hz; P = 0.002), with a trend versus BFR CONT (15.7 ± 3.5 Hz; P = 0.063). These findings indicate that, in physically active individuals, using BFR during exercise does not impair the recovery of neuromuscular function by 24 h post-exercise., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The abrupt cessation of ovarian hormone release is associated with declines in muscle contractile function, yet the impact of gradual ovarian failure on muscle contractility across peri-, early- and late-stage menopause remains unclear. In this study, a 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model was used to examine time course changes in muscle mechanical function. Plantar flexors of female mice (VCD: n = 10; CON: n = 8) were assessed at 40 (early perimenopause), 80 (late perimenopause), 120 (menopause onset) and 176 (late menopause) days post-initial VCD injection. A torque-frequency relationship was established across a range of frequencies (10-200 Hz). Isotonic dynamic contractions were elicited against relative loads (10-80% maximal isometric torque) to determine the torque-velocity-power relationship. Mice then performed a fatigue task using intermittent 100 Hz isometric contractions until torque dropped by 60%. Recovery of twitch, 10 Hz and 100 Hz torque were tracked for 10 min post-task failure. Additionally, intact muscle fibres from the flexor digitorum brevis underwent a fatigue task (50 repetitions at 70 Hz), and 10 and 100 Hz tetanic [Ca 2+ ] were monitored for 10 min afterward. VCD mice exhibited 16% lower twitch torque than controls across all time points. Apart from twitch torque, 10 Hz torque and 10 Hz tetanic [Ca 2+ ], where VCD showed greater values relative to pre-fatigue during recovery, no significant differences were observed between control and VCD mice during recovery. These results indicate that gradual ovarian failure has minimal detriments to in vivo muscle mechanical function, with minor alterations observed primarily for low-frequency stimulation during recovery from fatigue., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: Menopause is associated with impaired skeletal muscle contractile function. The temporal and mechanistic bases of this dysfunction are unknown. Using a mouse model of menopause, we identified how gradual ovarian failure affects single muscle fiber contractility., Study Design: Ovarian failure was chemically induced over 120 days, representing the perimenopausal transition. Mice were sacrificed and soleus and extensor digitorum longus muscles were dissected and chemically permeabilized for single fiber mechanical testing., Main Outcome Measures: Muscle fiber contractility was assessed via force, rate of force redevelopment, instantaneous stiffness, and calcium sensitivity., Results: Peak force and cross-sectional area of the soleus were, respectively, ~33 % and ~24 % greater following ovarian failure compared with controls (p < 0.05) with no differences in force produced by the extensor digitorum longus across groups (p > 0.05). Upon normalizing force to cross-sectional area there were no differences across groups (p > 0.05). Following ovarian failure, rate of force redevelopment of single fibers from the soleus was ~33 % faster compared with controls. There was no shift in the midpoint of the force‑calcium curve between groups or muscles (p > 0.05). However, following ovarian failure, Type I fibers from the soleus had a higher calcium sensitivity between pCa values of 4.5 and 6.2 compared with controls (p < 0.05), with no differences for Type II fibers or the extensor digitorum longus (p > 0.05)., Conclusions: In our model of menopause, alterations to muscle contractility were less evident than in ovariectomized models. This divergence across models highlights the importance of better approximating the natural trajectory of menopause during and after the transitional phase of ovarian failure on neuromuscular function., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Skeletal muscle contractile function is impaired in menopause and exercise may mitigate this decline. We used the 4-vinylcyclohexene diepoxide (VCD) model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high-intensity interval training (HIIT) can mitigate impairments. Sexually mature female CD-1 mice were assigned to one of three groups: control sedentary ( n = 5), VCD-sedentary ( n = 5), or VCD-training ( n = 5). Following ovarian failure (a 4-mo process), the VCD-training group underwent 8 wk of uphill HIIT. Mice were euthanized 8 wk after ovarian failure, representing late menopause. Single fibers from the soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected, chemically permeabilized, and mechanically tested. Single muscle fibers were maximally activated (pCa 4.5), then isotonic load clamps were performed to evaluate force-velocity-power relationships. Absolute force and peak power were 31.0% and 32.2% lower in VCD-sedentary fibers compared with control fibers, respectively, in both SOL and EDL muscles. Despite reductions in absolute force, there were no concomitant increases in contractile velocity to preserve power production. HIIT attenuated force loss in the VCD-training group such that peak force was not different from the control group across muscles and was partially effective at mitigating power loss (21.7% higher peak power in VCD-training compared with VCD-sedentary) but only in fast-type SOL fibers. These findings indicate that ovarian failure impairs dynamic contractile function-likely through a combination of lower force-generating capacity and slower shortening velocity-and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level. NEW & NOTEWORTHY We used the VCD model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high-intensity interval training (HIIT) can mitigate impairments. Our findings indicate that ovarian failure impairs dynamic contractile function-likely through a combination of lower force-generating capacity and slower shortening velocity-and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level.

Ultrasound-derived measurements of muscle fascicle length (FL) are often used to infer increases (chronic stretch or training) or decreases (muscle disuse or aging) in serial sarcomere number (SSN). Whether FL adaptations measured via ultrasound can truly approximate SSN adaptations has not been investigated. We casted the right hindlimb of 15 male Sprague-Dawley rats in a dorsiflexed position (i.e., stretched the plantar flexors) for 2 weeks, with the left hindlimb serving as a control. Ultrasound images of the soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were obtained with the ankle at 90° and full dorsiflexion for both hindlimbs pre and post-cast. Following post-cast ultrasound measurements, legs were fixed in formalin with the ankle at 90°, then muscles were dissected and fascicles were teased out for measurement of sarcomere lengths via laser diffraction and calculation of SSN. Ultrasound detected an 11% increase in soleus FL, a 12% decrease in LG FL, and an 8-11% increase in MG FL for proximal fascicles and at full dorsiflexion. These adaptations were partly reflected by SSN adaptations, with a 6% greater soleus SSN in the casted leg than the un-casted leg, but no SSN differences for the gastrocnemii. Weak relationships were observed between ultrasonographic measurements of FL and measurements of FL and SSN from dissected fascicles. Our results showed that ultrasound-derived FL measurements can overestimate an increase in SSN by ∼5%. Future studies should be cautious when concluding a large magnitude of sarcomerogenesis from ultrasound-derived FL measurements, and may consider applying a correction factor. NEW FINDINGS: What is the central question of this study? Measurements of muscle fascicle length via ultrasound are often used to infer changes in serial sarcomere number, such as increases following chronic stretch or resistance training, and decreases with ageing: does ultrasound-derived fascicle length accurately depict adaptations in serial sarcomere number? What is the main finding and its importance? Ultrasound detected an ∼11% increase in soleus fascicle length, but measurements on dissected fascicles showed the actual serial sarcomere number increase was only ∼6%; therefore, measurements of ultrasound-derived fascicle length can overestimate serial sarcomere number adaptations by as much as 5%., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Purpose: Exercise blood pressure (BP) responses are thought to be determined by relative exercise intensity (percent maximal voluntary contraction (MVC) strength). However, cross-sectional studies report that during a static contraction, higher absolute force is associated with greater BP responses to relative intensity exercise and subsequent muscle metaboreflex activation with postexercise circulatory occlusion (PECO). We hypothesized that a bout of unaccustomed eccentric exercise would reduce knee extensor MVC and subsequently attenuate BP responses to PECO., Methods: Continuous BP, heart rate, muscle oxygenation, and knee extensor electromyography were recorded in 21 young healthy individuals (female, n = 10) during 2 min of 20% MVC static knee extension exercise and 2 min of PECO, performed before and 24 h after 300 maximal knee extensor eccentric contractions to cause exercise-induced muscle weakness. As a control, 14 participants repeated the eccentric exercise 4 wks later to test whether BP responses were altered when exercise-induced muscle weakness was attenuated via the protective effects of the repeated bout effect., Results: Eccentric exercise reduced MVC in all participants (144 ± 43 vs 110 ± 34 N·m, P < 0.0001). BP responses to matched relative intensity static exercise (lower absolute force) were unchanged after eccentric exercise ( P > 0.99) but were attenuated during PECO (systolic BP: 18 ± 10 vs 12 ± 9 mm Hg, P = 0.02). Exercise-induced muscle weakness modulated the deoxygenated hemoglobin response to static exercise (64% ± 22% vs 46% ± 22%, P = 0.04). When repeated after 4 wks, exercise-induced weakness after eccentric exercise was attenuated (-21.6% ± 14.3% vs -9.3 ± 9.7, P = 0.0002) and BP responses to PECO were not different from control values (all, P > 0.96)., Conclusions: BP responses to muscle metaboreflex activation, but not exercise, are attenuated by exercise-induced muscle weakness, indicating a contribution of absolute exercise intensity on muscle metaboreflex activation., (Copyright © 2023 by the American College of Sports Medicine.)

During natural aging, skeletal muscle experiences impairments in mechanical performance due, in part, to changes in muscle architecture and size, notably with a loss of muscle cross-sectional area (CSA). Another important factor that has received less attention is the shortening of fascicle length (FL), potentially reflective of a decrease in serial sarcomere number (SSN). Interventions that promote the growth of new serial sarcomeres, such as chronic stretching and eccentric-biased resistance training, have been suggested as potential ways to mitigate age-related impairments in muscle function. Although current research suggests it is possible to stimulate serial sarcomerogenesis in muscle in old age, the magnitude of sarcomerogenesis may be less than in young muscle. This blunted effect may be partly due to age-related impairments in the pathways regulating mechanotransduction, muscle gene expression, and protein synthesis, as some have been implicated in SSN adaptation. The purpose of this review was to investigate the impact of aging on the ability for serial sarcomerogenesis and elucidate the molecular pathways that may limit serial sarcomerogenesis in old age. Age-related changes in mechanistic target of rapamycin (mTOR), insulin-like growth factor 1 (IGF-1), myostatin, and serum response factor signaling, muscle ring finger protein (MuRFs), and satellite cells may hinder serial sarcomerogenesis. In addition, our current understanding of SSN in older humans is limited by assumptions based on ultrasound-derived fascicle length. Future research should explore the effects of age-related changes in the identified pathways on the ability to stimulate serial sarcomerogenesis, and better estimate SSN adaptations to gain a deeper understanding of the adaptability of muscle in old age.

Background: Females are typically less fatigable than males during sustained isometric contractions at lower isometric contraction intensities. This sex difference in fatigability becomes more variable during higher intensity isometric and dynamic contractions. While less fatiguing than isometric or concentric contractions, eccentric contractions induce greater and longer lasting impairments in force production. However, it is not clear how muscle weakness influences fatigability in males and females during sustained isometric contractions., Methods: We investigated the effects of eccentric exercise-induced muscle weakness on time to task failure (TTF) during a sustained submaximal isometric contraction in young (18-30 years) healthy males (n = 9) and females (n = 10). Participants performed a sustained isometric contraction of the dorsiflexors at 35° plantar flexion by matching a 30% maximal voluntary contraction (MVC) torque target until task failure (i.e., falling below 5% of their target torque for ≥2 s). The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric contractions. Agonist and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles, respectively., Results: Males were ∼41% stronger than females. Following eccentric exercise both males and females experienced an ∼20% decline in maximal voluntary contraction torque. TTF was ∼34% longer in females than males prior to eccentric exercise-induced muscle weakness. However, following eccentric exercise-induced muscle weakness, this sex-related difference was abolished, with both groups having an ∼45% shorter TTF. Notably, there was ∼100% greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the males., Conclusion: This increase in antagonist activation disadvantaged females by decreasing their TTF, resulting in a blunting of their typical fatigability advantage over males., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Introduction: Following active lengthening or shortening contractions, isometric steady-state torque is increased (residual force enhancement; rFE) or decreased (residual force depression; rFD), respectively, compared to fixed-end isometric contractions at the same muscle length and level of activation. Though the mechanisms underlying this history dependence of force have been investigated extensively, little is known about the influence of exercise-induced muscle weakness on rFE and rFD., Purpose: Assess rFE and rFD in the dorsiflexors at 20%, 60%, and 100% maximal voluntary torque (MVC) and activation matching, and electrically stimulated at 20% MVC, prior to, 1 h following, and 24 h following 150 maximal eccentric dorsiflexion contractions., Methods: Twenty-six participants (13 male, 24.7 ± 2.0y; 13 female, 22.5 ± 3.6y) were seated in a dynamometer with their right hip and knee angle set to 110° and 140°, respectively, with an ankle excursion set between 0° and 40° plantar flexion (PF). MVC torque, peak twitch torque, and prolonged low frequency force depression were used to assess eccentric exercise-induced neuromuscular impairments. History-dependent contractions consisted of a 1 s isometric (40°PF or 0°PF) phase, a 1 s shortening or lengthening phase (40°/s), and an 8 s isometric (0°PF or 40°PF) phase., Results: Following eccentric exercise; MVC torque was decreased, prolonged low frequency force depression was present, and both rFE and rFD increased for all maximal and submaximal conditions., Conclusions: The history dependence of force during voluntary torque and activation matching, and electrically stimulated contractions is amplified following eccentric exercise. It appears that a weakened neuromuscular system amplifies the magnitude of the history-dependence of force., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: It is suggested that the early phase (< 50 ms) of force development during a muscle contraction is associated with intrinsic contractile properties, while the late phase (> 50 ms) is associated with maximal force. There are no direct investigations of single muscle fibre rate of force development (RFD) as related to joint-level RFD METHODS: Sixteen healthy, young (n = 8; 26.4 ± 1.5 yrs) and old (n = 8; 70.1 ± 2.8 yrs) males performed maximal voluntary isometric contractions (MVC) and electrically evoked twitches of the knee extensors to assess RFD. Then, percutaneous muscle biopsies were taken from the vastus lateralis and chemically permeabilized, to assess single fibre function., Results: At the joint level, older males were ~ 30% weaker and had ~ 43% and ~ 40% lower voluntary RFD values at 0-100 and 0-200 ms, respectively, than the younger ones (p ≤ 0.05). MVC torque was related to every voluntary RFD epoch in the young (p ≤ 0.001), but only the 0-200 ms epoch in the old (p ≤ 0.005). Twitch RFD was ~ 32% lower in the old compared to young (p < 0.05). There was a strong positive relationship between twitch RFD and voluntary RFD during the earliest time epochs in the young (≤ 100 ms; p ≤ 0.01). While single fibre RFD was unrelated to joint-level RFD in the young, older adults trended (p = 0.052-0.055) towards significant relationships between joint-level RTD and Type I single fibre RFD at the 0-30 ms (r 2  = 0.48) and 0-50 ms (r 2  = 0.49) time epochs., Conclusion: Electrically evoked twitches are good predictors of early voluntary RFD in young, but not older adults. Only the older adults showed a potential relationship between single fibre (Type I) and joint-level rate of force development., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Residual force enhancement (rFE) is characterized by increased steady-state isometric force following active muscle lengthening compared with a fixed-end isometric contraction at the same muscle length and level of neuromuscular activation. Many studies have characterized rFE in humans; however, the day-to-day reliability of rFE is unclear. We aimed to examine day-to-day reliability of rFE across various contraction types in the dorsiflexors in males and females. Twenty-five recreationally active young adults completed two visits, 1 week apart. Following determination of maximum voluntary contraction (MVC) strength, rFE was assessed during maximal voluntary effort, 20% MVC electrically stimulated, and 20% MVC torque-matching conditions. Each rFE condition was completed at two joint excursions: 0°-20° plantar flexion (PF) and 0°-40° PF. Intraclass correlation coefficients (ICC) assessed relative reliability and typical error of measurement (TEM), and the correlation variability of TEM (CV TEM ) assessed absolute reliability. Electrically stimulated contractions demonstrated the highest reliability at 40° PF (ICC: 0.9; CV TEM : 22.8%) and 20° PF (ICC: 0.8; CV TEM : 34.3%), followed by maximal voluntary contractions at 40° PF (ICC: 0.7; CV TEM : 55.1%) and 20° PF (ICC: 0.1; CV TEM : 81.1%). The torque-matching trials showed poor reliability for 20° and 40° PF (ICC: -0.1 to 0.3; CV TEM : 118.1%-155.2%). Our results demonstrate higher reliability of rFE when stretching to the descending limb of the torque-angle relationship compared with the plateau region, and in electrically stimulated compared with voluntary contractions in the dorsiflexors for both males and females.

To determine how heating affects dynamic joint position sense at the knee, participants (n = 11; F = 6) were seated in a HUMAC NORM dynamometer. The leg was passively moved through extension and flexion, and participants indicated when the 90° reference position was perceived, both at baseline (28.74 ± 2.43 °C) and heated (38.05 ± 0.16 °C) skin temperatures. Day 2 of testing reduced knee skin feedback with lidocaine. Directional error (actual leg angle-target angle) and absolute error (AE) were calculated. Heating reduced extension AE (baseline AE = 5.46 ± 2.39°, heat AE = 4.10 ± 1.97°), but not flexion. Lidocaine did not significantly affect flexion AE or extension AE. Overall, increased anterior knee-skin temperature improves dynamic joint position sense during passive knee extension, where baseline matching is poorer. Limited application of lidocaine to the anterior thigh, reducing some skin input, did not influence dynamic joint position sense, suggesting cutaneous receptors may play only a secondary role to spindle information during kinesthetic tasks. Importantly, cutaneous input from adjacent thigh regions cannot be ruled out as a contributor.

Adult aging is associated with a myriad of changes within the neuromuscular system, leading to reductions in contractile function of old adults. One of the consequences of these age-related neuromuscular adaptations is altered performance fatigability, which can limit the ability of old adults to perform activities of daily living. Whereas age-related fatigability during isometric tasks has been well characterized, considerably less is known about fatigability of old adults during dynamic tasks involving movement about a joint, which provides a more functionally relevant task compared with static contractions. This review provides a comprehensive summary of age-related fatigability during dynamic contractions, where the importance of task specificity is highlighted with a brief discussion of the potential mechanisms responsible for differences in fatigability between young and old adults. The angular velocity of the task is critical for evaluating age-related fatigability, as tasks that constrain angular velocity (i.e., isokinetic) produce equivocal age-related differences in fatigability, whereas tasks involving unconstrained velocity (i.e., isotonic-like) consistently induce greater fatigability for old compared with young adults. These unconstrained velocity tasks, which are more closely associated with natural movements, offer an excellent model to uncover the underlying age-related mechanisms of increased fatigability. Future work evaluating the mechanisms of increased age-related fatigability during dynamic tasks should be evaluated using contraction modes that are specific to the task (i.e., dynamic), rather than isometric, particularly for the assessment of spinal and supra spinal components. Advancing our understanding of age-related fatigability is likely to yield novel insights and approaches for improving mobility limitations in old adults.

Improved Ca 2+ sensitivity has been suggested as a mechanism behind enhancements in muscle mechanical function following eccentric training. However, little is known regarding the effects of eccentric training on single muscle fiber Ca 2+ sensitivity. Adult male Sprague-Dawley rats (sacrificial age ~18 weeks; mass = 400.1 ± 34.8 g) were assigned to an eccentric training (n = 5) or sedentary control group (n = 6). Eccentric training consisted of 4 weeks of weighted downhill running 3×/week at a 15° decline and 16 m/min for 35 min per day in 5-min bouts. After sacrifice, vastus intermedius single muscle fibers were dissected, chemically permeabilized, and stored until testing. Fibers (n = 63) were isolated, and standard Ca 2+ sensitivity, force, rate of force redevelopment (k tr ), and active instantaneous stiffness tests were performed using [Ca 2+ ] ranging from 7.0 to 4.5. Following all mechanical testing, fiber type was determined using SDS-PAGE. There was no difference in pCa 50 (i.e., [Ca 2+ ] needed to elicit half of maximal force) between groups or between fiber types. However, when comparing normalized force across pCa values, fibers from the control group produced greater forces than fibers from the trained group at lower Ca 2+ concentrations (p < 0.05), and this was most evident for Type I fibers (p = 0.002). Type II fibers produced faster (p < 0.001) k tr than Type I fibers, but there were no differences in absolute force, normalized force, or other measures of mechanical function between fibers from the trained and control groups. These findings indicate that eccentric training does not appear to improve single muscle fiber Ca 2+ sensitivity., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: The purpose of this study was to investigate associations of muscle quality indices with joint-level power-related measures in the knee extensors of thirty-two older males (65-88 years)., Methods: Muscle quality indices included: echo intensity, ratio of intracellular- to total water content (ICW/TW), and specific muscle strength. Echo intensity was acquired from the rectus femoris (EI RF ) and vastus lateralis (EI VL ) by ultrasonography. ICW/TW was computed from electrical resistance of the right thigh obtained by bioelectrical impedance spectroscopy. Specific muscle strength was determined as the normalized maximal voluntary isometric knee extension (MVIC) torque to estimated knee extensor volume. Isotonic maximal effort knee extensions with a load set to 20% MVIC torque were performed to obtain the knee extension power-related measures (peak power, rate of power development [RPD], and rate of velocity development [RVD]). Power and RPD were normalized to MVIC., Results: There were no significant correlations between muscle quality indices except between EI RF and EI VL (|r|≤ 0.253, P ≥ 0.162). EI RF was negatively correlated with normalized RPD and RVD (r ≤  - 0.361, P ≤ 0.050). ICW/TW was positively correlated with normalized peak power (r = 0.421, P = 0.020). Specific muscle strength was positively correlated with absolute peak power and RPD (r ≥ 0.452, P ≤ 0.012)., Conclusion: Knee extension power-related measures were lower in participants with higher EI, lower ICW/TW, and lower specific muscle strength, but the muscle quality indices may be determined by independent physiological characteristics., (© 2022. The Author(s).)

Increased serial sarcomere number (SSN) has been observed in rats following downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesised trained rats would produce greater net work output during work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a training or sedentary control group. Weight was added during downhill running via a custom-made vest, progressing from 5-15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (cyclic muscle length changes) were then performed about optimal muscle length (LO) at 1.5-3-Hz cycle frequencies and 1-7-mm length changes. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), and a less steep passive force-length curve than controls (P<0.05). There were no differences in collagen parameters (P>0.05). Net work output was greater (+78-209%) in trained than control rats for the 1.5-Hz work loops at 1 and 3-mm length changes (P<0.05), however, net work output was more related to maximum specific force (R2=0.17-0.48, P<0.05) than SSN (R2=0.03-0.07, P=0.17-0.86). Therefore, contrary to our hypothesis, training-induced sarcomerogenesis likely contributed little to the improvements in work loop performance. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Skeletal muscle has the remarkable ability to remodel and adapt, such as the increase in serial sarcomere number (SSN) or fascicle length (FL) observed after overstretching a muscle. This type of remodeling is termed longitudinal muscle fascicle growth, and its impact on biomechanical function has been of interest since the 1960s due to its clinical applications in muscle strain injury, muscle spasticity, and sarcopenia. Despite simplified hypotheses on how longitudinal muscle fascicle growth might influence mechanical function, existing literature presents conflicting results partly due to a breadth of methodologies. The purpose of this review is to outline what is currently known about the influence of longitudinal muscle fascicle growth on mechanical function and suggest future directions to address current knowledge gaps and methodological limitations. Various interventions indicate longitudinal muscle fascicle growth can increase the optimal muscle length for active force, but whether the whole force-length relationship widens has been less investigated. Future research should also explore the ability for longitudinal fascicle growth to broaden the torque-angle relationship's plateau region, and the relation to increased force during shortening. Without a concurrent increase in intramuscular collagen, longitudinal muscle fascicle growth also reduces passive tension at long muscle lengths; further research is required to understand whether this translates to increased joint range of motion. Finally, some evidence suggests longitudinal fascicle growth can increase maximum shortening velocity and peak isotonic power; however, there has yet to be direct assessment of these measures in a neurologically intact model of longitudinal muscle fascicle growth.

This study investigated associations of fatigue resistance determined by an exercise-induced decrease in neuromuscular power with prefatigue neuromuscular strength and power of the knee extensors in 31 older men (65-88 years). A fatigue task consisted of 50 consecutive maximal effort isotonic knee extensions (resistance: 20% of prefatigue isometric maximal voluntary contraction torque) over a 70° range of motion. The average of the peak power values calculated from the 46th to 50th contractions during the fatigue task was normalized to the prefatigue peak power value, which was defined as neuromuscular fatigue resistance. Neuromuscular fatigue resistance was negatively associated with prefatigue maximal power output (r = -.530) but not with prefatigue maximal voluntary contraction torque (r = -.252). This result highlights a trade-off between prefatigue maximal power output and neuromuscular fatigue resistance, implying that an improvement in maximal power output might have a negative impact on neuromuscular fatigue resistance.

Time-dependent measures consisting of rate of torque development (RTD), rate of velocity development (RVD), and rate of neuromuscular activation can be used to evaluate explosive muscular performance, which becomes critical when performing movements throughout limited ranges of motion (ROM). In this study, we investigated how restricting ROM influences power production while also exploring the relationship with time-dependent measures before and after isometric resistance training. Using a HUMAC NORM dynamometer, seven males (27 ± 7 yr) and six females (22 ± 3 yr) underwent 8 wk of maximal isometric dorsiflexion training 3 days/wk. One leg was trained at 0° [short-muscle tendon unit (MTU) length] and the other at 40° of plantar flexion (long-MTU length). RTD and rate of neuromuscular activation were evaluated during "fast" maximal isometric contractions. Power, RVD, and rate of neuromuscular activation were assessed during maximal isotonic contractions in four conditions [small (40°-30° of plantar flexion) ROM at 10% and 50% MVC; large (40°-0° of plantar flexion) ROM at 10% and 50% MVC] for both legs, pre- and posttraining. Despite no change in rate of neuromuscular activation following training, peak power, RTD, and RVD increased at both MTU lengths ( P < 0.05). Strong relationships ( R = 0.73) were observed between RTD and peak power in the small ROM, indicating that fast time-dependent measures are critical for optimal performance when ROM is constrained. Meanwhile, strong relationships ( 2 = 0.90) between RVD and power were observed at the 50% load, indicating that RVD is critical when limited by load and ROM is not confined. Maximal isometric dorsiflexion training can be used to improve time-dependent measures (RTD, RVD) to minimize power attenuation when ROM is restricted. R Power output was greater in the unrestricted than restricted ROM, and there were strong relationships between rate of torque development (RTD) and velocity development (RVD) with peak power. RTD and RVD had the strongest relationships with power when ROM was restricted and unrestricted, respectively. Following 8 wk of isometric training, discrepancies in power between restricted and unrestricted ROM were reduced. Increasing RTD through isometric training increased power in dynamic movements, especially when ROM was restricted.2 = 0.90) between RVD and power were observed at the 50% load, indicating that RVD is critical when limited by load and ROM is not confined. Maximal isometric dorsiflexion training can be used to improve time-dependent measures (RTD, RVD) to minimize power attenuation when ROM is restricted. NEW & NOTEWORTHY Power output was greater in the unrestricted than restricted ROM, and there were strong relationships between rate of torque development (RTD) and velocity development (RVD) with peak power. RTD and RVD had the strongest relationships with power when ROM was restricted and unrestricted, respectively. Following 8 wk of isometric training, discrepancies in power between restricted and unrestricted ROM were reduced. Increasing RTD through isometric training increased power in dynamic movements, especially when ROM was restricted.

A combination of factors during the SARS-CoV-2 pandemic led to a disproportionately high mortality rate among residents of long-term care homes in Canada and around the globe. Retrospectively, some of these factors could have been avoided or minimized. Many infection control approaches recommended by public health experts and regulators, while well intended to keep people safe from disease exposure, threatened other vital aspects of health and well-being. Furthermore, focusing narrowly on infection control practices does not address long-standing operational and infrastructural factors that contributed significantly to the pandemic toll. In this article, we review traditional (ie. institutional) long-term care practices that were associated with increased risk during the pandemic and highlight one transformational model (the Green House Project) that worked well to protect the lives and livelihood of people within congregate care settings. Drawing on this evidence, we identify specific strategies for necessary and overdue improvements in long-term care homes.

Despite compelling muscular structure and function changes resulting from blood flow restricted (BFR) resistance training, mechanisms of action remain poorly characterized. Alterations in tissue O 2 saturation (TSI%) and metabolites are potential drivers of observed changes, but their relationships with degree of occlusion pressure are unclear. We examined local TSI% and blood lactate (BL) concentration during BFR training to failure using different occlusion pressures on strength, hypertrophy, and muscular endurance over an 8-week training period. Twenty participants (11 males/9 females) trained 3/wk for 8 wk using high pressure (100% resting limb occlusion pressure, LOP; 20% one-repetition maximum (1RM)), moderate pressure (50% LOP, 20%1RM), or traditional resistance training (TRT; 70%1RM). Strength, size, and muscular endurance were measured pre/post training. TSI% and BL were quantified during a training session. Despite overall increases, no group preferentially increased strength, hypertrophy, or muscular endurance ( p  > 0.05). Neither TSI% nor BL concentration differed between groups ( p  > 0.05). Moderate pressure resulted in greater accumulated deoxygenation stress (TSI% × time) (-6352 ± 3081, -3939 ± 1835, -2532 ± 1349 au for moderate pressure, high pressure, and TRT, p  = 0.018). We demonstrate that BFR training to task-failure elicits similar strength, hypertrophy, and muscular endurance changes to TRT. Further, varied occlusion pressure does not impact these outcomes or elicit changes in TSI% or BL concentrations. Novelty: Training to task failure with low-load blood flow restriction elicits similar improvements to traditional resistance training, regardless of occlusion pressure. During blood flow restriction, altering occlusion pressure does not proportionally impact tissue O 2 saturation nor blood lactate concentrations.

Human biological aging from maturity to senescence is associated with a gradual loss of muscle mass and neuromuscular function. It is not until very old age (>80 years) however, that these changes often manifest into functional impairments. A driving factor underlying the age-related loss of muscle mass and function is the reduction in the number and quality of motor units (MUs). A MU consists of a single motoneuron, located either in the spinal cord or the brain stem, and all of the muscle fibres it innervates via its peripheral axon. Throughout the adult lifespan, MUs are slowly, but progressively lost. The compensatory process of collateral reinnervation attempts to recapture orphaned muscle fibres following the death of a motoneuron. Whereas this process helps mitigate loss of muscle mass during the latter decades of adult aging, the neuromuscular system has fewer and larger MUs, which have lower quality connections between the axon terminal and innervated muscle fibres. Whether this process of MU death and degradation can be attenuated with habitual physical activity has been a challenging question of great interest. This review focuses on age-related alterations of the human neuromuscular system, with an emphasis on the MU, and presents findings on the potential protective effects of lifelong physical activity. Although there is some discrepancy across studies of masters athletes, if one considers all experimental limitations as well as the available literature in animals, there is compelling evidence of a protective effect of chronic physical training on human MUs. Our tenet is that high-levels of physical activity can mitigate the natural trajectory of loss of quantity and quality of MUs in old age., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Following a shortening or lengthening muscle contraction, torque produced in the isometric steady state is lower (residual torque depression; rTD) or higher (residual torque enhancement; rTE), respectively, compared to a purely isometric contraction at the same final muscle length and level of activation. This is referred to as the history dependence of force. When matching a given torque level, there is greater muscle activation (electromyography; EMG) following shortening and less activation following lengthening. Owing to these differences in neuromuscular activation, it is unclear whether perception of effort is altered by the history dependence of force during plantar-flexion., Methods: Experiment 1 tested whether perception of effort differed between the rTD and rTE state when torque was matched. Experiment 2 tested whether perception of effort differed between the rTD and rTE state when EMG was matched. Finally, experiment 3 tested whether EMG differed between the rTD and rTE state when perception of effort was matched., Results: When torque was matched, both EMG and perception of effort were higher in the rTD compared to rTE state. When EMG was matched, torque was lower in the rTD compared to rTE state while perception of effort did not differ between the two states. When perception of effort was matched, torque was lower in the rTD compared to rTE state and EMG did not differ between the two states., Conclusion: The combined results from these experiments indicate that the history dependence of force alters one's perception of effort, dependent on the level of motor command., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Males have larger blood pressure (BP) responses to relative-intensity static handgrip exercise compared with females. Controlling for absolute load (maximal voluntary contraction (MVC)) abolishes these differences. Whether similar observations exist during large muscle mass exercise or dynamic contractions, and the mechanisms involved, remains unknown., Methods: BP, heart rate, muscle oxygenation (near-infrared spectroscopy), and rectus femoris EMG were recorded in 28 males and 17 females during 10% and 30% MVC static (120 s) and isokinetic dynamic (180 s; 1:2 work-to-rest ratio; angular velocity, 60°·s-1) knee extensor exercise. Static and dynamic exercises were completed on separate visits, in a randomized order. Sex differences were examined with and without statistical adjustment of MVC (ANCOVA)., Results: Males had larger systolic BP responses (interaction, P < 0.0001) and muscle deoxygenation (interaction, P < 0.01) than did females during 10% static exercise, with no difference in EMG (interaction, P = 0.67). Peak systolic BP was correlated with MVC (r = 0.55, P = 0. 0001), and adjustment for MVC abolished sex differences in systolic BP (interaction, P = 0.3). BP, heart rate, muscle oxygenation/deoxygenation, and EMG responses were similar between sexes during 30% static exercise (interaction; all, P > 0.2), including following adjustment for MVC (all, P > 0.1). Males had larger systolic BP responses during dynamic exercise at 10% and 30% (interaction; both, P = 0.01), which were abolished after adjustment for MVC (interaction; both, P > 0.08). Systolic BP responses were correlated with absolute MVC and stroke volume responses during 10% (r = 0.31, P = 0.04; r = 0.61, P < 0.0001, respectively) and 30% (r = 0.48, P = 0.001; r = 0.59, P < 0.0001, respectively)., Conclusions: Absolute contraction intensity can influence systolic BP responses to 10% but not 30% MVC static, as well as 10% and 30% MVC dynamic knee extensor exercise, and should be considered in cross-sectional comparisons of exercise BP., (Copyright © 2021 by the American College of Sports Medicine.)

Natural adult aging is associated with declines in skeletal muscle performance, including impaired Ca 2+ sensitivity and a slowing of rapid force production (rate of force redevelopment; k tr ). The purpose of this study was to investigate the relationship between impaired Ca 2+ sensitivity and k tr of single muscle fibres from young and older adults. Participants included 8 young (22-35 yrs) and 8 older (60-81 yrs) males who were living independently. A percutaneous muscle biopsy of the vastus lateralis of each participant was performed. Single muscle fibre mechanical tests included maximal Ca 2+ -activated force (P o ), force-pCa curves, and k tr . We showed a decrease in pCa 50 in old type II fibres compared to young, indicating impaired Ca 2+ sensitivity in older adults. The k tr behaved in a Ca 2+ -dependent manner such that with increasing [Ca 2+ ], k tr increases, to a plateau. Interestingly, k tr was not different between young and old muscle fibres. Furthermore, we found strong associations between pCa 50 and k tr in both old type I and type II fibres, such that those fibres with lower Ca 2+ sensitivity had a slowed k tr . This Ca 2+ association, combined with impaired Ca 2+ handling in older adults suggests a potential Ca 2+ -dependent mechanism affecting the transition from weakly- to strongly-bound cross-bridge states, leading to a decline in skeletal muscle performance. Future research is needed to explore the role alterations to Ca 2+ sensitivity/handling could be playing in age-related whole muscle performance declines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

High-intensity eccentric exercise can lead to muscle damage and weakness. The 'repeated bout effect' (RBE) can attenuate these impairments when performing a subsequent bout. The influence of eccentric exercise-induced muscle damage on low-frequency force production is well-characterized; however, it is unclear how eccentric exercise and the RBE affect torque production across a range of stimulation frequencies (i.e., the torque-frequency relationship). We investigated the influence of an initial (Bout 1) and repeated bout (Bout 2) of eccentric exercise on the elbow flexor torque-frequency relationship. Eleven males completed two bouts of high-intensity eccentric elbow flexions, 4 weeks apart. Torque-frequency relationships were constructed at baseline and 0.5, 24, 48, 72, 96, and 168 h following both bouts via percutaneous stimulation at 1, 6, 10, 20, 30, 40, 50, and 100 Hz. Serum creatine kinase activity, self-reported muscle soreness, and isometric maximum voluntary contraction torque indirectly inferred the presence of muscle damage following Bout 1, and attenuation of muscle damage following Bout 2. Torque amplitude at all stimulation frequencies was impaired 30 min following eccentric exercise, however, torque at lower (1-10 Hz) and higher frequencies (40-100 Hz) recovered within 24 h while torque across the middle frequency range (20-30 Hz) recovered by 48 h. No between-bout differences were detected in absolute or normalized torque at any stimulation frequency, indicating no protective RBE on the elbow flexor torque-frequency relationship., Competing Interests: Declaration of Competing Interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We investigated age-related changes to fascicle length, sarcomere length and serial sarcomere number (SSN), and how this affects passive force. Following mechanical testing to determine passive force, the medial gastrocnemius muscle of young (n=9) and old (n=8) Fisher 344BN hybrid rats was chemically fixed at the optimal muscle length for force production; individual fascicles were dissected for length measurement, and laser diffraction was used to assess sarcomere length. Old rats had ∼14% shorter fascicle lengths than young rats, which was driven by a ∼10% reduction in SSN, with no difference in sarcomere length (∼4%). Passive force was greater in the old than in the young rats at long muscle lengths. Shorter fascicle lengths and reduced SSN in the old rats could not entirely explain increased passive forces for absolute length changes, owing to a slight reduction in sarcomere length in old rats, resulting in similar sarcomere length at long muscle lengths., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

High-intensity unaccustomed eccentric contractions result in weakness and power loss because of fatigue and muscle damage. Through the repeated bout effect (RBE), adaptations occur, then damage and weakness are attenuated following a subsequent bout. However, it is unclear whether the RBE protects peak power output. We investigated the influence of the RBE on power production and estimated fatigue- and damage-induced neuromuscular impairments following repeated high-intensity eccentric contractions. Twelve healthy adult males performed 5 sets of 30 maximal eccentric elbow flexions and repeated an identical bout 4 weeks later. Recovery was tracked over 7 days following both bouts. Reduced maximum voluntary isometric contraction torque, and increased serum creatine kinase and self-reported soreness indirectly inferred muscle damage. Peak isotonic power, time-dependent measures - rate of velocity development (RVD) and rate of torque development (RTD) - and several electrophysiological indices of neuromuscular function were assessed. The RBE protected peak power, with a protective index of 66% 24 h after the second eccentric exercise bout. The protection of power also related to preserved RVD ( R 2 = 0.61, P < 0.01) and RTD ( R 2 The repeated bout effect protects peak isotonic power. Protection of peak power relates to preserved rates of torque and velocity development, but more so rate of velocity development. The repeated bout effect has little influence on indices of neuromuscular fatigue.P < 0.01). Furthermore, the RBE's protection against muscle damage permitted the estimation of fatigue-associated neuromuscular performance decrements following eccentric exercise. Novelty: The repeated bout effect protects peak isotonic power. Protection of peak power relates to preserved rates of torque and velocity development, but more so rate of velocity development. The repeated bout effect has little influence on indices of neuromuscular fatigue.

Purpose: This study aimed to investigate the effects of blood flow restriction (BFR) combined with electrical muscle stimulation (EMS) on skeletal muscle mass and strength during a period of limb disuse., Methods: Thirty healthy participants (22 ± 3 yr; 23 ± 3 kg·m-2) were randomly assigned to control (CON; n = 10), BFR alone (BFR; n = 10), or BFR combined with EMS (BFR + EMS; n = 10). All participants completed unloading of a single leg for 14 d, with no treatment (CON), or while treated with either BFR or BFR + EMS (twice daily, 5 d·wk-1). BFR treatment involved arterial three cycles of 5-min occlusion using suprasystolic pressure, each separated by 5 min of reperfusion. EMS (6 s on, 15 s off; 200 μs; 60 Hz; 15% maximal voluntary contraction [MVC]) was applied continuously throughout the three BFR cycles. Quadriceps muscle mass (whole-thigh lean mass via dual-energy x-ray absorptiometry and vastus lateralis [VL] muscle thickness via ultrasound) and strength (via knee extension MVC) were assessed before and after the 14-d unloading period., Results: After limb unloading, whole-thigh lean mass decreased in the control group (-4% ± 1%, P < 0.001) and BFR group (-3% ± 2%, P = 0.001), but not in the BFR + EMS group (-0.3% ± 3%, P = 0.8). VL muscle thickness decreased in the control group (-4% ± 4%, P = 0.005) and was trending toward a decrease in the BFR group (-8% ± 11%, P = 0.07) and increase in the BFR + EMS group (+5% ± 10%, P = 0.07). Knee extension MVC decreased over time (P < 0.005) in the control group (-18% ± 15%), BFR group (-10% ± 13%), and BFR + EMS group (-18% ± 15%), with no difference between groups (P > 0.5)., Conclusion: Unlike BFR performed in isolation, BFR + EMS represents an effective interventional strategy to attenuate the loss of muscle mass during limb disuse, but it does not demonstrate preservation of strength., (Copyright © 2020 by the American College of Sports Medicine.)

The history dependence of force is an intrinsic property of muscle whereby a muscle actively shortened or lengthened to an isometric steady-state produces less (residual force depression; rFD) or more force (residual force enhancement; rFE), respectively, than a purely isometric contraction at the same muscle length and level of activation. Previous studies on the modifiability of the history dependence of force have been inconclusive, and none have attempted to modify rFD and rFE through isometric resistance training biased to short vs long muscle-tendon unit (MTU) lengths. We tested maximal voluntary rFD and rFE in seven males and six females before and after 8 weeks of maximal isometric dorsiflexion training 3 days/wk. Participants trained one leg at 0° of plantar flexion (short-MTU training) and one at 40° of plantar flexion (long-MTU training). Ultrasonography of the tibialis anterior assessed resting muscle architecture. Tibialis anterior fascicle length decreased by ~3% following short-MTU training (P = .03) and increased by ~4% following long-MTU training (P = .01). rFD did not change following training at either MTU length (absolute rFD: P = .53; percent rFD: P = .51), nor did rFE (absolute rFE: P = .78; percent rFE: P = .80), with no relationships between the change in fascicle length and the change in percent rFD (R 2  = .01, P = .62) nor rFE (R 2  = .001, P = .88). Our data indicate that voluntary rFD and rFE were not modified by isometric training and not related to the fascicle length adaptations we observed., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Following active muscle shortening, steady-state isometric force is less than a purely isometric contraction at the same muscle length and level of activation; this is known as residual force depression (rFD). It is unknown whether rFD at the single muscle fiber level can be modified via training. Here we investigated whether rFD in single muscle fibers is modifiable through downhill and uphill running in the extensor digitorum longus (EDL) and soleus (SOL) muscles in rats. Rats were run uphill or downhill 5 days/week for 4 weeks. After muscles were dissected and chemically permeabilized, single fibers were tied between a length controller and force transducer, transferred to an activating solution, with ATP and pCa of 4.2 for mechanical testing. rFD was quantified after active fiber shortening from an average sarcomere length (SL) of 3.1-2.5 µm at a relative speed of 0.15 fiber lengths/s (slow) and 0.6 fiber lengths/s (fast). rFD was calculated as the difference in force (normalized to cross-sectional area) during the isometric steady-state phase following active shortening and the purely isometric contraction. In addition to rFD, mechanical work of shortening and stiffness depression were also calculated. rFD was present for both the EDL (6-15%) and SOL (1-2%) muscles, with no effect of training. rFD was greater for the EDL than SOL which closely corresponded to the greater stiffness depression in the EDL, indicating a greater inhibition of cross-bridge attachments. These results indicate that while rFD was observed, training did not appear to alter this intrinsic history-dependent property of single muscle fibers., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Residual torque enhancement (rTE) is the increase in torque observed during the isometric steady state following active muscle lengthening when compared with a fixed-end isometric contraction at the same muscle length and level of neuromuscular activation. In the rTE state, owing to an elevated contribution of passive force to total force production, less active force is required, and there is a subsequent reduction in activation. In vivo studies of rTE reporting an activation reduction are often performed using a dynamometer, where participants contract against a rigid restraint, resisting a torque motor. rTE has yet to be investigated during a position task, which involves the displacement of an inertial load with positional control., Methods: A total of 12 participants (6 males, 6 females; age = 22.8 ± 1.1 years, height = 174.7 ± 8.6 cm, mass = 82.1 ± 37.7 kg; mean ± SD) completed torque- and position-matching tasks at 60% maximum voluntary contraction for a fixed-end isometric contraction and an isometric contraction following active lengthening of the ankle dorsiflexors., Results: There were no significant differences in activation between torque- and position-matching tasks (p = 0.743), with ∼27% activation reduction following active lengthening for both task types (p < 0.001)., Conclusion: These results indicate that rTE is a feature of voluntary, position-controlled contractions. These findings support and extend previous findings of isometric torque-control conditions to position-controlled contractions that represent different tasks of daily living., (Copyright © 2020. Production and hosting by Elsevier B.V.)

Caron, KE, Burr, JF, and Power, GA.. The effect of a stretch-shortening cycle on muscle activation and muscle oxygen consumption: a study of history-dependence. J Strength Cond Res 34(11): 3139-3148, 2020-Stretch-shortening cycles (SSCs) are observed in a variety of human movements and are associated with increases in performance. Few studies have considered the effects of stretch-induced residual force enhancement (rFE) and shortening-induced residual force depression (rFD) during an SSC, and none have considered these properties during voluntary contractions. With force matched via a robotically resisted Smith machine, we hypothesized that in the isometric steady-state following an SSC (a) muscle activation (electromyography) of the knee and hip extensors would be greater and (b) muscle oxygen consumption be higher than the reference isometric condition (ISO), but less than the rFD condition. Subjects (n = 20, male, 24.9 ± 3.9 year) performed a squat exercise over 100-140° knee angle and a matched ISO at the top and bottom of the squat. After active shortening, the vastus medialis (VM), vastus lateralis (VL), and gluteus maximus (GM) showed activation increase in the rFD-state compared with ISO (∼15%, ∼11%, and ∼25% respectively). During the isometric steady-state following the SSC, there was no difference in activation as compared with ISO for VM, VL, but GM showed an activation increase of ∼15%. VM and VL showed an activation increase in the rFD-state compared with the isometric steady-state following SSC (∼16 and ∼10% respectively). Muscle oxygen consumption (tissue saturation index) was not different during the isometric steady-states following rFD and SSC compared with ISO. During a voluntary SSC exercise, the activation increase expected in the FD-state was attenuated, with no change in muscle oxygen consumption. The concomitant role of rFE and rFD during a voluntary position-matched SSC seems to counteract shortening-induced activation increase and may optimize movement economy.

The increase or decrease in isometric force following active muscle lengthening or shortening, relative to a reference isometric contraction at the same muscle length and level of activation, are referred to as residual force enhancement (rFE) and residual force depression (rFD), respectively. The purpose of these experiments was to investigate the trainability of rFE and rFD on the basis of serial sarcomere number (SSN) alterations to history-dependent force properties. Maximal rFE/rFD measures from the soleus and extensor digitorum longus (EDL) of rats were compared after 4 weeks of uphill or downhill running with a no-running control. SSN adapted to the training: soleus SSN was greater with downhill compared with uphill running, while EDL demonstrated a trend towards more SSN for downhill compared with no running. In contrast, rFE and rFD did not differ across training groups for either muscle. As such, it appears that training-induced SSN adaptations do not modify rFE or rFD at the whole-muscle level., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Introduction: The passive mechanical behavior of skeletal muscle represents both important and generally underappreciated biomechanical properties with little attention paid to their trainability. These experiments were designed to gain insight into the trainability of muscle passive mechanical properties in both single fibers and fiber bundles. Methods: Rats were trained in two groups: 4 weeks of either uphill (UH) or downhill (DH) treadmill running; with a third group as sedentary control. After sacrifice, the soleus (SOL), extensor digitorum longus (EDL), and vastus intermedius (VI) were harvested. One hundred seventy-nine bundles and 185 fibers were tested and analyzed using a cumulative stretch-relaxation protocol to determine the passive stress and elastic modulus. Titin isoform expression was analyzed using sodium dodecyl sulfate vertical agarose gel electrophoresis (SDS-VAGE). Results: Single fibers: passive modulus and stress were greater for the EDL at sarcomere lengths (SLs) ≥ 3.7 μm (modulus) and 4.0 μm (stress) with DH training compared to UH training and lesser for the SOL (SLs ≥ 3.3 μm) with DH training compared with control; there was no effect of UH training. Vastus intermedius was not affected by either training protocol. Fiber bundles: passive modulus and stress were greater for the EDL at SLs ≥ 2.5 μm (modulus) and 3.3 μm (stress) in the DH training group as compared with control, while no affects were observed in either the SOL or VI for either training group. No effects on titin isoform size were detected with training. Conclusion: This study demonstrated that a trainability of passive muscle properties at both the single fiber and fiber bundle levels was not accompanied by any detectable changes to titin isoform size., (Copyright © 2020 Noonan, Mashouri, Chen, Power and Brown.)

Neuromuscular fatigue impairs motor coordination, movement stability, and proprioception, which further decreases performance. A neuromechanical coupling exists between foot sole cutaneous mechanoreceptors and motoneurons of the lower limb, however, the contribution of skin sensory input on muscle fatigue remains unclear. The purpose of this study was to determine if the presence of cutaneous stimulation could mitigate the effect of fatigue of the plantar flexor muscles during a sustained isometric task at 30% maximal voluntary contraction (MVC). Participants ( N = 16, age 24.1 ± 2.6 yr) underwent a 30% isometric plantar flexor fatiguing task in a seated position with hip, knee, and ankle angle at 80°, 100°, and 90°, respectively, with intermittent MVCs until task failure. Failure was defined as when the participant could no longer maintain 30% MVC for a minimum of two seconds. Throughout the protocol, electrical stimulation was applied to either the right heel, right metatarsals, or no stimulation. A subset of participants ( N = 6) underwent an additional condition with electrical stimulation applied to the left arm. MVCs were also conducted intermittently throughout recovery for 30 min. Foot sole cutaneous stimulation mitigated fatigue, as demonstrated by an ~15% increased time to task failure (TTF) compared with the control condition. When normalized to TTF, MVC torque amplitude was not different at each time epoch, which indicated that each %MVC was maintained longer into the fatigue task during the heel and metatarsal stimulation conditions However, there was no significant effect of cutaneous stimulation on recovery. The results indicate that cutaneous stimulation may serve as a feasible means to mitigate fatigue. NEW & NOTEWORTHY Cutaneous coupling with lower limb motor neurons has long been known. We set out to establish whether this pathway could serve a purpose other than muscular modulation during standing and walking. We found that during a submaximal contraction of the plantar flexor muscles, the addition of intermittent cutaneous stimulation to the skin of the foot sole resulted in an increase in time to task failure by 15%, which was over a minute longer in duration. We conclude that skin stimulation may serve as a mechanism to mitigate fatigue.