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Skeletal muscle weakness in old age: Underlying mechanisms
Abstract
Maintenance of muscle mass and strength contributes to mobility which impacts on quality of life. Although muscle atrophy, declining strength, and physical frailty are generally accepted as inevitable concomitants of aging, the causes are unknown. Clarification of the mechanisms responsible for these changes would enhance our understanding of the degree to which they are preventable or treatable. The decline in muscle function between maturity and old age is similar for muscles of many different animals including human beings, and is typified by the decreases of approximately 35% in maximum force, approximately 30% in maximum power, and 20% in normalized force (kN.m-2) and power (W.kg-1) of extensor digitorum longus (EDL) muscles in old compared with adult mice. Much of the age-associated muscle atrophy and declining strength may be explained by motor unit remodeling which appears to occur by selective denervation of muscle fibers with reinnervation by axonal sprouting from an adjacent innervated unit. Muscles in old mice appear more susceptible to injury than muscles in young or adult mice and have a decreased capacity for recovery. The process of age-related denervation may be aggravated by an increased susceptibility of muscles in old animals to contraction-induced injury coupled with impaired capacity for regeneration.
... Las limitaciones funcionales y la disminución del consumo de proteína se han descrito como factores clave, que pueden favorecer la pérdida progresiva de masa y fuerza muscular en los adultos mayores (6) . Ellos tienen requerimientos de proteína mayores que la población general, por lo que la European Society for Clinical Nutrition and Metabolism (ESPEN) recomienda una ingesta entre 1 y 1,5 g/kg al día para prevenir la pérdida de masa muscular (7) . ...
... En este sentido, la combinación de ambas terapias, ejercicio de resistencia y suplementación con proteína aislada de soya podría incrementar la masa muscular esquelética o fuerza en adultos mayores con dinapenia o baja masa muscular (15) ; sin embargo, no se dispone de suficiente evidencia que respalde esta hipótesis. prensil de mano en mujeres (17 [15,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] kg frente a 20 [16,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] kg; p = 0,0001), pero no en hombres; y aumento de la masa muscular (39,1 [35,6-44,3] kg frente a 39,9 [35,9-45,5]; p = 0,024) en ambos sexos. La masa grasa corporal total y la grasa visceral disminuyeron en los dos grupos. ...
... (17 [15,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] kg vs. 20 [16,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] kg; p = 0,0001), mas não em homens, e aumento da massa muscular (39,1 [35,6-44,3] kg vs. 39,9 [35,9,5-45,5]; p = 0,024) em ambos os sexos; a massa de gordura corporal total e a gordura visceral diminuíram em ambos os grupos. ...
Introducción: la sarcopenia es una condición que se puede asociar con la edad, caracterizada por la declinación funcional y estructural del músculo esquelético estriado. La suplementación con proteína, en combinación con ejercicio de resistencia, es el tratamiento principal para contrarrestar la sarcopenia o dinapenia en adultos mayores. El objetivo de este estudio es evaluar el efecto de la suplementación con proteína aislada de soya y el ejercicio de resistencia sobre la fuerza muscular y composición corporal en adultos mayores, que viven en una comunidad urbana marginal de Ecuador. Métodos: se realizó un estudio cuasiexperimental, con una duración de 12 semanas en 70 adultos mayores (65 años o más) con dinapenia o baja masa muscular. Los participantes recibieron 10 g de proteína aislada de soya al día y realizaron entrenamiento de fuerza. Se realizó un análisis estadístico descriptivo. Las variables se probaron con T de Student, U de Mann Whitney y Chi cuadrado. Resultados: se encontró un aumento estadísticamente significativo en la fuerza prensil de mano en mujeres (17 [15,5-21] kg frente a 20 [16,7-23] kg; p = 0,0001), pero no en hombres; y aumento de la masa muscular (39,1 [35,6-44,3] kg frente a 39,9 [35,9-45,5]; p = 0,024) en ambos sexos. La masa grasa corporal total y la grasa visceral disminuyeron en los dos grupos. Conclusión: la suplementación con proteína aislada de soya junto con ejercicio de resistencia durante 12 semanas mejoró la fuerza muscular en mujeres y la composición corporal en hombres y mujeres en la muestra estudiada. Palabras clave: suplementos dietéticos, terapia por ejercicio, sarcopenia, adulto mayor, fuerza muscular.
... On this basis we postulate that lower limb strength may also be a correlate of cognitive function in old age, because it is associated with the aging of the CNS. Loss of strength is caused mainly by muscle atrophy, which in turn is caused largely by a loss of fibers and, to a less extent, a reduction in fiber size (Brooks & Faulkner, 1994). It is thought that the reduction in skeletal muscle fibers is caused by a process of denervation and reinnervation of individual fibers caused by continuous loss of motor neurons in the spinal cord (Brooks & Faulkner, 1994;Lexell, Downham, & Sjostrom, 1986). ...
... Loss of strength is caused mainly by muscle atrophy, which in turn is caused largely by a loss of fibers and, to a less extent, a reduction in fiber size (Brooks & Faulkner, 1994). It is thought that the reduction in skeletal muscle fibers is caused by a process of denervation and reinnervation of individual fibers caused by continuous loss of motor neurons in the spinal cord (Brooks & Faulkner, 1994;Lexell, Downham, & Sjostrom, 1986). Eventually, fibers become permanently denervated and are replaced by fat and fibrous tissue. ...
The authors investigated the association between sensorimotor variables indicative of biological aging and cognition. A community sample of 202 women ages 60–86 was assessed on 5 measures of lower limb strength, visual contrast sensitivity (VisCS), and reaction time (RT). Hierarchical multiple regression revealed that the sensorimotor variables explained age-related variance in measures of reasoning and total variance in measures of reasoning after education, health, mood, and physical activity were controlled for. It is concluded that in addition to better known predictors of cognitive aging, such as RT and VisCS, lower limb strength is an important predictor of performance on cognitive tests.
... To the best of our knowledge, only a few studies have examined the effects of both age and sex on muscle stiffness with the biceps brachii in a relatively stretched position [17,18]. Muscle function generally declines with aging, especially in thigh muscles [19]. Nevertheless, no studies have yet addressed the interactive effects of age and sex on the muscle stiffness of thigh muscles. ...
... This idea is merely speculation at this moment, but these findings suggest that the age at which fibrosis begins to occur varies depending on the site within the body. Given that muscle function generally declines with aging, especially in thigh muscles [19], our finding implies that the accelerated increase in VL stiffness that occurs after an individual passes their late 40s may be an important therapeutic target for developing effective treatments and programs that preserve and improve quality of life. ...
Skeletal muscle fibrosis occurs with aging and has been suggested to impair muscle performance, thereby decreasing quality of life. Recently, muscle stiffness, a surrogate measure of muscle fibrosis, was noninvasively quantified as the shear modulus using ultrasound shear wave elastography (SWE) in humans. We aimed to investigate thigh muscle stiffness in females and males, respectively, across a broad range of ages by using SWE. Eighty-six community-dwelling Japanese people who were aged 30 to 79 years and did not regularly exercise participated in this study. The vastus lateralis (VL) shear modulus was measured at three different knee joint angles: full extension, 90° of flexion, and full flexion. There were no significant main effects of sex or age on the VL shear modulus in full extension or 90° of flexion of the knee. However, the VL shear modulus in knee full flexion was significantly smaller in females than in males and increased with age from 47.9 years. The results suggest that the accelerated increase in VL stiffness that occurs after an individual passes their late 40s may be an important therapeutic target for developing effective treatments and programs that preserve and improve quality of life.
... In these studies, F max was only made to vary within small ranges [19] or proportionally for all muscles [13], and the effects of muscle-or subject-specificity have not been investigated [20]. Additionally, MSK models do not typically account for loss of muscle strength typically associated to ageing [3,21], which can be both subject-and muscle-specific [22]. ...
... (Sartorius), compared to literature values for healthy young mixed-sex adults (quantified between 20% and 40% from the reported mean and SD) [25] and even more when isolating the female component (except for the Tensor fasciae latae muscle). The V M calculated from our cohort remained consistently smaller to those from young females, except for the Vastus intermedius, likely due to ageing-related muscles volume loss [3,21]. ...
The ability of muscles to produce force depends, among others, on their anatomical features and it is altered by ageing-associated weakening. However, a clear characterisation of these features, highly relevant for older individuals, is still lacking. This study hence aimed at characterising muscle volume, length, and physiological cross-sectional area (PCSA) and their variability, between body sides and between individuals, in a group of post-menopausal women. Lower-limb magnetic resonance images were acquired from eleven participants (69 (7) y. o., 66.9 (7.7) kg, 159 (3) cm). Twenty-three muscles were manually segmented from the images and muscle volume, length and PCSA were calculated from this dataset. Personalised maximal isometric force was then calculated using the latter information. The percentage difference between the muscles of the two lower limbs was up to 89% and 22% for volume and length, respectively, and up to 84% for PCSA, with no recognisable pattern associated with limb dominance. Between-subject coefficients of variation reached 36% and 13% for muscle volume and length, respectively. Generally, muscle parameters were similar to previous literature, but volumes were smaller than those from in-vivo young adults and slightly higher than ex-vivo ones. Maximal isometric force was found to be on average smaller than those obtained from estimates based on linear scaling of ex-vivo -based literature values. In conclusion, this study quantified for the first time anatomical asymmetry of lower-limb muscles in older women, suggesting that symmetry should not be assumed in this population. Furthermore, we showed that a scaling approach, widely used in musculoskeletal modelling, leads to an overestimation of the maximal isometric force for most muscles. This heavily questions the validity of this approach for older populations. As a solution, the unique dataset of muscle segmentation made available with this paper could support the development of alternative population-based scaling approaches, together with that of automatic tools for muscle segmentation.
... Muscle strength decreases with ageing, 1 and its maintenance reduces the prevalence of functional limitation. 2 Among community-dwelling older adults, leg function is highly predictive of Age-related loss of muscle strength refers to loss of both neuromuscular function and muscle mass and is the primary cause for muscle decline. [7][8][9] However, other factors may contribute to the loss of muscle strength with ageing. 10 In addition to muscle quantity, muscle quality (muscle strength relative to muscle mass) may be another determinant of loss of muscle strength with ageing. ...
... 30 Decline of muscle strength with ageing is a determinant of loss of muscle mass and muscle quality. 9,11 Understanding the correlations between physical performance and muscle mass or muscle quality in obese and normal-weight older women may help them to maintain or improve their physical performance. ...
... Edges below a given threshold are not shown (for illustration purposes). muscle strength (Brooks & Faulkner, 1994). Young and healthy individuals demonstrate a great ability to adapt force output, quickly and accurately, in response to a stimulus (Vaillancourt & Newell, 2003). ...
There are numerous studies comparing young and old adults in terms of muscle coordination in standard tasks (e.g., walking, reaching) and small variations of them. These tasks might hide differences: individuals would converge to similar behavior as they practice these throughout life. Also, we are unaware of studies that considered the muscle recruitment nested dynamics. For this reason, our study evaluated how young and old women coordinate and control the movement system while performing an unusual redundant motor control task through the network physiology approach. We acquired electro-myographic signals from nine leg muscles of the dominant and non-dominant limbs during maximum voluntary isometric contractions (knee extension and flexion) and co-contraction bouts. Our results showed that young participants presented higher peak torque output, with similar EMG variability, compared to older participants. Considering firing rate frequencies, old and young women demonstrated different traits for network clustering and efficiency for the task. Age seems to affect muscle coordination at higher frequencies, even with a similar number of muscle synergies, indicating that younger women might have more integrated synergies than older women. The findings also point to differential muscle coordination adaptability.
... MGF is upregulated following mechanical stretch, injury and/or electrical s mula on of skeletal muscle in vivo [17,18,19], and promotes skeletal muscle prolifera on in vitro [20,21,22]. Reduced MGF expression seen with age is associated with reduced ability to respond to mechanical overload [20,23,24,25]. MGF has also been shown to play a role in other ssues, including the brain, where it promotes hippocampal neurogenesis, neuronal guidance and growth, motor unit and motoneuron survival [26,27,28,29], and in heart [30], tendons [31] and bone-marrow [32]. ...
Overactive bladder (OAB) is a urological symptom complex defined by urinary urgency. It can have a devastating impact on an individual's quality of life and leads to significant financial cost. Insulin-like growth factor 1 (IGF-1) is a protein hormone involved in a broad range of processes including cell proliferation and differentiation. IGF-1 is also regulated through alternative splicing. While the primary IGF-1Ea transcript is highly expressed in liver, the alternative IGF-1Ec transcript encodes the proteolytically-derived MGF peptide and has been primarily studied in skeletal muscle. MGF has been shown to stimulate satellite cell proliferation following tissue mechanical stretch or injury, but the role of MGF in smooth muscle, such as the detrusor muscle of the bladder, has been little explored. The aim of this study was to explore the expression of MGF in bladder biopsies from patients with OAB and age-matched controls.
We show using immunohistochemistry that MGF is widely expressed in bladder tissue. Quantification of MGF expression by western blot showed that average MGF expression is more than doubled in OAB biopsies compared to controls (mean MGF in OAB=0.51 +/-0.1, n=23; mean MGF in controls=0.22 +/-0.07, n=9; p=0.05). Furthermore, there is an inverse correlation between MGF protein levels and symptom severity, as determined by the urodynamic parameter maximum cystometric capacity (correlation=0.53, p=0.03 n=16). MGF expression was highest in OAB biopsies with strong expression of the muscle cell marker DES. Combined with our observation that MGF induces cell proliferation in primary bladder cultures, our data suggests that high MGF expression in OAB patients may represent an attempted protective response in the bladder.
... This suggests that agedrelated changes to fibers responsible for carrying afferent information may play a role in increases in proprioceptive error. Second, as we age, there is loss of both extrafusal and intrafusal muscle fibers (Brooks and Faulkner, 1994). Previous studies have found that, with age, the number of muscle spindles decrease in number over time and receive less innervation than in "young" muscle (Swallow, 1966;Swash and Fox, 1972;Proske and Gandevia, 2012;Landelle et al., 2021). ...
Previous work has identified age-related declines in proprioception within a narrow range of limb movements. It is unclear whether these declines are consistent across a broad range of movement characteristics that more closely represent daily living. Here we aim to characterize upper limb error in younger and older adults across a range of movement speeds and distances. The objective of this study was to determine how proprioceptive matching accuracy changes as a function of movement speed and distance, as well as understand the effects of aging on these accuracies. We used an upper limb robotic test of proprioception to vary the speed and distance of movement in two groups: younger (n = 20, 24.25 ± 3.34 years) and older adults (n = 21, 63 ± 10.74 years). The robot moved one arm and the participant was instructed to mirror-match the movement with their opposite arm. Participants matched seven different movement speeds (0.1–0.4 m/s) and five distances (7.5–17.5 cm) over 350 trials. Spatial (e.g., End Point Error) and temporal (e.g., Peak Speed Ratio) outcomes were used to quantify proprioceptive accuracy. Regardless of the speed or distance of movement, we found that older controls had significantly reduced proprioceptive matching accuracy compared to younger control participants (p ≤ 0.05). When movement speed was varied, we observed that errors in proprioceptive matching estimates of spatial and temporal measures were significantly higher for older adults for all but the slowest tested speed (0.1 m/s) for the majority of parameters. When movement distance was varied, we observed that errors in proprioceptive matching estimates were significantly higher for all distances, except for the longest distance (17.5 cm) for older adults compared to younger adults. We found that the magnitude of proprioceptive matching errors was dependent on the characteristics of the reference movement, and that these errors scaled increasingly with age. Our results suggest that aging significantly negatively impacts proprioceptive matching accuracy and that proprioceptive matching errors made by both groups lies along a continuum that depends on movement characteristics and that these errors are amplified due to the typical aging process.
... In the absence of nerve activity, muscle will atrophy; muscle mass will be reduced; and muscle strength, fiber diameterm and quantity will be reduced in varying degrees. [12][13][14] Although sciatic nerve injury belongs to peripheral neuropathy, relevant literature reported that ligating the sciatic nerve will induce severe pain and lead to the atrophy of related muscles. 15 Therefore, FSN is hoped to be used to treat the injured nerve and muscle tissue, improve mitochondrial function, and prevent muscle atrophy. ...
To observe the effects of Fu's subcutaneous needling (FSN) and acupuncture treatment on the mitochondrial structure and function of the skeletal muscle tissue of rats with sciatica. Forty Sprague–Dawley rats were divided into control, model, acupuncture, and FSN groups (10 each) according to a random number table. The control group was left untreated. Rats in the FSN group were treated with FSN once every 2 days for three times, respectively (days 1, 3, 5, and 7), to cooperate with reperfusion approach. The acupuncture group was treated at the same timeline as that of the FSN group. Changes in the mechanical pain threshold, mitochondrial ultrastructure, mitochondrial citrate synthase (CS) activities, mitochondrial respiratory chain complex II, and mitochondrial COX- I protein expression in the skeletal muscle of rats treated with different treatments were compared with those of the model group. The pain thresholds of the rats were remarkably higher after FSN treatment and acupuncture, and the pain threshold of the FSN group was higher than that of the acupuncture group. Compared with the control group, the mitochondria of the model group had a damaged ultrastructure, were arranged in a disorganized manner, accumulated under the basement membrane, and appeared vacuolated with autophagosomes. The state of mitochondria in the FSN group was close to that in the control group and was remarkably better than that in the acupuncture group. The activities of mitochondrial CS and respiratory chain complex II in the skeletal muscle of the treated rats decreased compared with the control group (P<0.05), and their levels were better in the FSN group than in the acupuncture group (P<0.05). FSN treatment for 1 week considerably improved the pain thresholds and improved the skeletal muscle mitochondrial ultrastructure and mitochondrial function in rats with sciatica.
... Particularly, an assessment of muscle performance is essential for the early recognition of physical function decline [9]. Muscle function depends on muscle mass, strength, stiffness, and its contractile properties [9], predominantly in the lower extremities [10]. In addition, the elderly who suffer a fall have, overall, poorer physical function than non-fallers [11]. ...
The aim of this study is to compare the muscle strength, balance ability, thickness, and stiffness of the tibialis anterior and gastrocnemius muscle in the elderly, with (fallers) and without (non-fallers) fall experience, and confirmed the correlation between the variables mentioned above and muscle stiffness in the faller. We selected 122 elderly participants, comprising 40 fallers and 82 non-fallers, and measured the muscle strength of the tibialis anterior (TA) and the gastrocnemius (GA). Balance ability was measured by the functional reach test (FRT), timed up and go test (TUG), short physical performance battery (SPPB), and gait speed (GS). We used shear wave elastography (SWE) to determine the thickness of the TA and the medial (GAmed) and lateral head (GAlat) of the gastrocnemius and the stiffness during relaxation and contraction. Balance ability, except muscle strength, was significantly lower in fallers compared with non-fallers. The GAmed and GAlat thickness were significantly lower in fallers than that in non-fallers. In fallers, the thickness, rest, and contractive stiffness of GAmed were correlated with the FRT, GS, SPPB. Low rest and GAmed contractive stiffness were related to lower balance ability in fallers. The muscle stiffness measurement using SWE was a novel method to assess potential fall risk.
... Generally, aging models are divided into two categories: natural aging models and accelerated aging models. In the process of aging, naturally aging mice develop many phenotypes similar to normal human aging like cataracts [3] and muscle weakness [4]. For example, the most well-known strain of mice, C57BL/6, have a lifespan of two to three years, while naked mole-rats can live up to 30 years. ...
With the global increase of the elderly population, the improvement of the treatment for various aging-related diseases and the extension of a healthy lifespan have become some of the most important current medical issues. In order to understand the developmental mechanisms of aging and aging-related disorders, animal models are essential to conduct relevant studies. Among them, mice have become one of the most prevalently used model animals for aging-related studies due to their high similarity to humans in terms of genetic background and physiological structure, as well as their short lifespan and ease of reproduction. This review will discuss some of the common and emerging mouse models of accelerated aging and related chronic diseases in recent years, with the aim of serving as a reference for future application in fundamental and translational research.
... Former study has shown that motor neurons damage in the skeletal muscle has a trophic role and in the absence of neural activity, it reduces muscle mass and diameter and a number of muscle fibers. 27 When the muscle loses its stimulatory action as a result of motor neuron damage, it quickly becomes atrophic. Thus, muscle mass and diameter decrease, apoptosis occurs in myofibers 28 and the number of muscle fibers reduces. ...
Skeletal muscle atrophy induced by denervation is one of the common disorders in traumatic nerve injuries. The aim of this study was the evaluation of histomorphometrical changes of extensor digitorum longus muscle after denervation and its regeneration by tissue engineering. Ninety adult male Wistar rats were randomly divided into six main groups (n = 15) in three time periods (2, 4 and 8 weeks; n = 5). Control group was treated without surgery, in transection (Tr) group left sciatic nerve was transected, in scaffold (S) group only collagen gel scaffold was used, in mast cell (MC) group mast cells were used, mesenchymal stem cell (MSC) group was treated with mesenchymal stem cells and in MC+MSC group, mast cells along with mesenchymal stem cells were used. In the cellular groups, the scaffold and cells were mixed and placed in the transected nerve gap. The average diameter of muscle fibers, ratio of the muscle fibers nuclei to the fibrocytes nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fibers number (mn/mf), the average ratio of blood vessels to muscle fibers number (v/mf) and muscles weight in Tr group were the lowest compared to the other groups; but, in cellular and S groups, amelioration was observed according to the time period. However, in MC+MSC group, there were the highest ameliorative results. This study revealed that simultaneous use of MCs and MSCs mixed with collagen gel scaffold can be considered as a suitable approach to improve denervated skeletal muscle atrophy associated with sciatic nerve injury.
... In younger individuals, the loss of muscle mass is reversible, whereas, in older subjects, the muscle loss appears irrecoverable. With age, there is an increased susceptibility to contraction-induced injury and a decreased ability to recover from injury leading to muscle atrophy and weakness [76]. As the abundance and recruitment of satellite cells or muscle stem cells are low in the ageing myofibrils, skeletal muscle regeneration, growth, and maintenance are severely impaired [77]. ...
Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support. Although the origin of chronic fatigue is multifactorial, the MF in illness conditions is intrinsically linked to the occurrence of muscle loss. The sequence of events leading to chronic fatigue can be schematically denoted as: trigger (genetic or pathological) -> molecular outcome within the muscle cell -> muscle wasting -> loss of muscle function -> occurrence of chronic muscle fatigue. The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting, thereby helping us understand how we could prevent or treat this debilitating condition.
... It has been well known that aging is associated with major changes in the neuromuscular system (reviewed in Grabiner and Enoka 1995;Spirduso et al. 2005). These include loss of muscle mass (sarcopenia), progressive death of α-motoneurons, as well as neurons in a number of brain structures (Rodgers and Evans 1993;Booth et al. 1994;Brooks and Faulkner 1994;Eisen et al. 1996;Erim et al. 1999;Dinse 2006). These changes are accompanied by reinnervation of some of the orphan muscle fibers as well as by plastic changes within the CNS. ...
We revisit the concept of synergy based on the recently translated classical book by Nikolai Bernstein (On the construction of movements, Medgiz, Moscow 1947; Latash, Bernstein’s Construction of Movements, Routledge, Abingdon 2020b) and progress in understanding the physics and neurophysiology of biological action. Two aspects of synergies are described: organizing elements into stable groups (modes) and ensuring dynamical stability of salient performance variables. The ability of the central nervous system to attenuate synergies in preparation for a quick action—anticipatory synergy adjustments—is emphasized. Recent studies have demonstrated synergies at the level of hypothetical control variables associated with spatial referent coordinates for effectors. Overall, the concept of synergies fits naturally the hierarchical scheme of control with referent coordinates with an important role played by back-coupling loops within the central nervous system and from peripheral sensory endings. Further, we review studies showing non-trivial changes in synergies with development, aging, fatigue, practice, and a variety of neurological disorders. Two aspects of impaired synergic control—impaired stability and impaired agility—are introduced. The recent generalization of the concept of synergies for non-motor domains, including perception, is discussed. We end the review with a list of unresolved and troubling issues.
... The impact of muscle loss is exacerbated by the corresponding decline in the quality of the preserved muscle (e.g., amount of force per unit volume). These deficits, together with increased susceptibility to injury, reduced recovery, and proprioceptive decline [59,[67][68][69], predispose the risk of falls and related injuries [70,71], which are linked to morbidity and mortality [72,73]. Sarcopenia has enormous social and economic benefits: a 10% reduction in prevalence alone would result in savings of well over a billion dollars [74]. Despite significant advances in understanding the molecular alterations in aging, the pathophysiology of age-associated muscle weakness remains unclear. ...
The neuromuscular junction (NMJ) is a specialized synapse that bridges the motor neuron and the skeletal muscle fiber and is crucial for conversion of electrical impulses originating in the motor neuron to action potentials in the muscle fiber. The consideration of contributing factors to skeletal muscle injury, muscular dystrophy and sarcopenia cannot be restricted only to processes intrinsic to the muscle, as data show that these conditions incur denervation-like findings, such as fragmented NMJ morphology and corresponding functional changes in neuromuscular transmission. Primary defects in the NMJ also influence functional loss in motor neuron disease, congenital myasthenic syndromes and myasthenia gravis, resulting in skeletal muscle weakness and heightened fatigue. Such findings underscore the role that the NMJ plays in neuromuscular performance. Regardless of cause or effect, functional denervation is now an accepted consequence of sarcopenia and muscle disease. In this short review, we provide an overview of the pathologic etiology, symptoms, and therapeutic strategies related to the NMJ. In particular, we examine the role of the NMJ as a disease modifier and a potential therapeutic target in neuromuscular injury and disease.
... [1][2][3] This phenomenon, widely known as sarcopenia, has been directly linked to fracture risk, bone fragility, disability, and injurious falls. 4 Agingrelated pathologies and comorbidities, such as diabetes, 5 hypertension, 6 and cardiovascular disease, 7 have been likewise associated with sarcopenia and decreased muscle strength. Moderate to vigorous physical activity is protective against the adverse effects of sarcopenia. ...
Aging well is directly associated to a healthy lifestyle. The focus of this paper is to relate individual wellness with medical image features. Non-linear trimodal regression analysis (NTRA) is a novel method that models the radiodensitometric distributions of x-ray computed tomography (CT) cross-sections. It generates 11 patient-specific parameters that describe the quality and quantity of muscle, fat, and connective tissues. In this research, the relationship of these 11 NTRA parameters with age, physical activity, and lifestyle is investigated in the 3,157 elderly volunteers AGES-I dataset. First, univariate statistical analyses were performed, and subjects were grouped by age and self-reported past (youth-midlife) and present (within 12 months of the survey) physical activity to ascertain which parameters were the most influential. Then, machine learning (ML) analyses were conducted to classify patients using NTRA parameters as input features for three ML algorithms. ML is also used to classify a Lifestyle index using the age groups. This classification analysis yielded robust results with the lifestyle index underlying the relevant differences of the soft tissues between age groups, especially in fat and connective tissue. Univariate statistical models suggested that NTRA parameters may be susceptible to age and differences between past and present physical activity levels. Moreover, for both age and physical activity, lean muscle parameters expressed more significant variation than fat and connective tissues.
... The possible reasons for this increased fragility are the natural changes in the musculoskeletal system related to aging (i.e., sarcopenia, osteoporosis). The loss of muscle mass and strength (Brooks and Faulkner, 1994) decrease the traction force provided by the tendon on the bone and therefore, reducing the bone mineral density (Hannan et al., 2000). This reduces the capacity to absorb the kinetic energy during the impact (i.e., MVC), and potentially producing more severe injuries. ...
... GING IS ACCOMPANIED BY A PROGRESSIVE DECLINE in skeletal muscle mass, which in severe cases may result in decreased muscle strength and impaired physical performance (ie, sarcopenia). 1 Low muscle mass (LMM) is strongly linked with fall, fracture, and frailty, which may lead to a loss of mobility and independence. [2][3][4] Multiple factors are involved in the process of muscle mass loss, 5 and of these, nutrition, especially protein intake, is one of the most important and modifiable factors. 6,7 Intake and bioavailability of dietary protein appear to decrease with age. 5 An inadequate supply of protein disturbs not only muscle protein metabolism but also skeletal muscle transcription, accelerating muscle mass loss in older adults. ...
Background
Few studies have investigated the effect of long-term protein supplementation alone on muscle health in older adults with low lean mass.
Objective
To determine the effect of whey, soy or whey-soy blended protein supplementation on lean muscle mass and physical performance in older adults with low lean mass.
Design
A 4-arm randomized controlled trial.
Participants/setting
Chinese older adults (n = 123, 65-79 years) with low lean mass (appendicular skeletal muscle index < 7.0 kg/m² in men and < 5.4 kg/m² in women) living in the urban area of Guangzhou participated between October 2015 and June 2016.
Intervention
Participants were randomly assigned to receive approximately 16 g/d of whey, soy, or whey-soy blend protein or maintained habitual diets in control group for 6 months.
Main outcome measures
Lean mass, handgrip strength, and physical performance (gait speed, chair stand test, and Short Physical Performance Battery) were assessed at baseline and 6 months.
Statistical analyses
Two-way analysis of variance with the main effects of treatment and time and treatment × time interaction and analysis of covariance was used to determine differences in outcomes.
Results
Appendicular skeletal muscle index, lean mass, percent lean mass in legs and appendicular areas, gait speed, and Short Physical Performance Battery score were maintained in the treatment groups and decreased in the control group, resulting in significant reduction in these variables from baseline in the control compared with treatment groups (all P < .01; percent differences between treatment and control groups ranged from 80% to 156%). The chair stand test time at month 6 decreased from baseline in the treatment groups and increased in the control group, resulting in a significant increase in the control compared with treatment groups (all P < .01; percent differences between treatment and control groups ranged from 132% to 155%). Handgrip strength remained unchanged. There were no significant differences in outcomes among treatment groups.
Conclusions
Supplementation with whey, soy, or whey-soy blended protein for 6 months equally maintained lean muscle mass and physical performance in older adults with low lean mass.
... Physiological and pathological studies show that innervation and systemic factors exert a strong influence on skeletal muscle mass, composition and function (Delbono, 2003;Larsson et al., 2019). Sarcopenia is associated with: (a) excitation-contraction uncoupling (Delbono, 2011a;Delbono et al., 1995;Wang et al., 2002), which diminishes muscle specific force (force normalized to cross-sectional area) (Gonzalez et al., 2000a, b;Wang et al., 2000); (b) decreased number of muscle fibers as well as fiber atrophy (Dutta, 1997;Lexell, 1995); (c) changes in fiber type (Frontera et al., 2000;Larsson et al., 1991); (d) diminished muscle power related to decreased maximal isometric force and slower sliding of actin on myosin (Brooks and Faulkner, 1994;Hook et al., 1999); (e) impaired recovery after eccentric contraction (Faulkner et al., 1993); and (f) deposit of intra-and extra-myocellular lipids with consequent changes in skeletal muscle quality (Choi et al., 2012). Motor and/or sympathetic muscle denervation trigger and/or exacerbate some of these processes. ...
Examining neural etiologic factors’role in the decline of neuromuscular function with aging is essential to our understanding of the mechanisms underlying sarcopenia, the age-dependent decline in muscle mass, force and power. Innervation of the skeletal muscle by both motor and sympathetic axons has been established, igniting interest in determining how the sympathetic nervous system (SNS) affect skeletal muscle composition and function throughout the lifetime. Selective expression of the heart and neural crest derivative 2 gene in peripheral SNs increases muscle mass and force regulating skeletal muscle sympathetic and motor innervation; improving acetylcholine receptor stability and NMJ transmission; preventing inflammation and myofibrillar protein degradation; increasing autophagy; and probably enhancing protein synthesis. Elucidating the role of central SNs will help to define the coordinated response of the visceral and neuromuscular system to physiological and pathological challenges across ages.
This review discusses the following questions: (1) Does the SNS regulate skeletal muscle motor innervation? (2) Does the SNS regulate presynaptic and postsynaptic neuromuscular junction (NMJ) structure and function? (3) Does sympathetic neuron (SN) regulation of NMJ transmission decline with aging? (4) Does maintenance of SNs attenuate aging sarcopenia? and (5) Do central SN group relays influence sympathetic and motor muscle innervation?
... Hence, the anaerobic power was harder to maintain especially to elderly athletes because the decline of maximal anaerobic power as measured in athletes by vertical jumping had been found to be a 10% decreased per decade (Grassi et al., 1991). This is because it had been found that the functions of skeletal muscles become gradually impaired with advancing age (Brooks & Faulkner, 1994). ...
The focus of the study was to find out the effect of interval training on anaerobic power among the Majlis Perbandaran Subang Jaya (MPSJ's) Sepak Takraw players. There were MPSJ 14 players. The test was conducted at MPSJ hall in SS 15 Subang Jaya. The data was collected using the Sergeant's Jump and the 40 meters sprint test (pre test and post test) after eight (8) weeks of treatment program. The subjects trained for 3 days a week. The post test attained in order to determine the effect of interval treatment on the subjects anaerobic power. The data was processed by SPSS. The t-test and paired sample T-test was used, the paired sample t-test showed result of both Sergeant's Jump and 40 meters sprint significantly improved with t = 6.753, p = .000 < .05 and t = 13.683, p = .000< .05 respectively. The mean score of subjects in the pre-test of 40 meters sprint was 5.229 second while the Sergeant's Jump was 51.79 cm. Where else, the post-test, the mean score was 5.000 seconds for 40 meters sprint and 53.50 cm for Sergeant's Jump test, this indicated that there was significant effect of interval training on anaerobic power of MPSJ's Sepak Takraw players.
... The cause for this may be multifactorial with possible causes being age, sarcopenia, or a combination of both [12]. There is about a 25-40% decrease in muscle volume between the 3rd and 7th decade of life [12][13][14]. This means that the age difference of 3 years between our groups would only account for 1.5-3% difference in muscles size and that this finding is still important. ...
Introduction and hypothesis:
Intraabdominal pressure acts on the pelvic floor through an aperture surrounded by bony and muscular structures of the pelvis. A small pilot study showed the area of the anterior portion of this plane is larger in pelvic organ prolapse. We hypothesize that there is a relationship between prolapse and anterior (APA) and posterior (PPA) pelvic cross-sectional area in a larger, more diverse population.
Study design:
MRIs from 30 prolapse subjects and 66 controls were analyzed in this case-control study. The measurement plane was tilted to approximate the level of the levator ani attachments. Three evaluators made measurements. Patient demographic characteristics were compared using Wilcoxon rank-sum and Fisher's exact tests. A multivariable logistic regression model identified factors independently associated with prolapse.
Results:
Controls were 3.7 years younger and had lower parity, but groups were similar in terms of race, height, and BMI. Cases had a larger APA (p < 0.0001), interspinous diameter (ISD) (p = 0.001), anterior-posterior (AP) diameter (p = 0.01), and smaller total obturator internus muscle (OIM) area (p = 0.002). There was no difference in the size of the PPA(p = 0.12). Bivariate logistic regression showed age (p = 0.007), parity (p = 0.009), ISD (p = 0.002), AP diameter (p = 0.02), APA (p < 0.0001), and OIM size (p = 0.01) were significantly associated with prolapse; however, PPA was not (p = 0.12). After adjusting for age, parity, and major levator defect, prolapse was significantly associated with increased anterior pelvic area (p = 0.001).
Conclusions:
We confirm that a larger APA and decreasing OIM area are associated with prolapse. The PPA was not significantly associated with prolapse.
... A particular condition of frailty in the elderly is skeletal muscle atrophy or sarcopenia [33,34]. The progressive loss of muscle mass produces a decline in both the force and the function of the tissue. ...
Oxidative stress is known to be involved in the etiology of sarcopenia, a progressive loss of muscle mass and force related to elderly incapacity. A successful intervention to prevent this condition has been exercise-based therapy. Metformin (MTF), an anti-diabetic drug with pleiotropic effects, is known to retain redox homeostasis. However, the combined use of MTF with exercise has shown controversial experimental results. Our research group has shown that MTF-treatment does not limit the benefits provided by exercise, probably by inducing a hormetic response. Hence, our aim was to evaluate the effect of exercise in combination with MTF-treatment on the redox state of old female Wistar rats. Animals were divided into six groups; three groups preformed exercise on a treadmill for 5 days/week for 20 months and the other three were sedentary. Also, two groups of each, exercised and sedentary animals were treated with MTF for 6 or 12 months correspondingly, beside the untreated groups. Rats were euthanized at 24 months. Muscular functionality was analyzed as the relation between the lean mass free of bone with respect to the grip strength. Superoxide dismutase, catalase, and glutathione peroxidase content, enzymatic activity and redox state were determined in the gastrocnemius muscle. Our results showed that the exercised group treated with MTF for 12 months presented higher GSH/GSSG rate and high antioxidant scavenging power in contrast to the MTF-treatment for 6 months, where the beneficial effect was less noticeable.
Graphic abstract
... The decline in skeletal muscle mass (SMM) begins as early as 35 years of age and accelerates after 60 years (4) . Age-related loss of skeletal muscle, which leads to the onset of sarcopenia in severe cases, can increase the risk of functional impairment and mortality (5)(6)(7) . It is worthy to note that muscle mass reduction is an important feature of 'pre-sarcopenia' (8) . ...
A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 year in middle-aged adults. A total of 1242 participants aged 41-60 years from the Guangzhou Nutrition and Health Study (GNHS) 2011-2013 and 2014-2017 with body composition measurements by dual-energy x-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e., percentage loss or increase) in SMM of legs, limbs, and appendicular skeletal mass index (ASMI) over 3-year follow-up [β(SE): 0.322 (0.157), 0.309 (0.142), and 0.303 (0.145), respectively; P < 0.05]. The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all P -trend < 0.05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.
... The possible reasons for this increased fragility are the natural changes in the musculoskeletal system related to aging (i.e., sarcopenia, osteoporosis). The loss of muscle mass and strength (Brooks and Faulkner, 1994) decrease the traction force provided by the tendon on the bone and therefore, reducing the bone mineral density (Hannan et al., 2000). This reduces the capacity to absorb the kinetic energy during the impact (i.e., MVC), and potentially producing more severe injuries. ...
ging and obesity are two key areas of research as risk factors leading to motor vehicle collisions (MVCs). However, only a few studies identified obese older drivers as an at-risk population of MVC (i.e., older than 65 years old with Body Mass Index greater than 30 kg/m2). This paper aims to review the literature related to aging, obesity, and MVCs. Extensive literature searches were conducted, and the results are presented in a narrative review of the literature, in order to discuss the risk for involvement in MVC as well as the solutions for this population. Extrinsic factors are components of the “built environment” that decrease road safety for this population and poor fit of the vehicle through their inappropriate design for this population. The intrinsic factors are the autonomy and the health status of the driver. Health status are challenges associated with obesity and aging that increase the prevalence of being part in a MVC and that increase risk of morbidity and mortality during or following a collision. Finally, some prevention strategies are presented for consideration. There is a need to inform public policy makers on the additional risk factors associated with aging and obesity for MVCs.
... myostatin and members of the ubiquitin-proteasome system). 3 Sarcopenia is characterized by muscle wasting during ageing, 4 progressive loss of myofiber size and number, 5 and a shift in myofiber from Type II to Type I. 6,7 These last two changes may occur at a very old age. ...
Background
The aim of the present investigation is to evaluate the effect of the overexpression of inducible 70‐kDa heat shock protein (HSP70) on sarcopenic muscles of aged mice.
Methods
Tibialis anterior muscles of aged and young transgenic mice overexpressing HSP70 and wild‐type mice were evaluated. Old mice were treated with the HSP inducer O‐[3‐piperidino‐2‐hydroxy‐1‐propyl]‐nicotinic amidoxime (BGP‐15) for 10 days, and their muscles were analysed.
Results
Old HSP70 transgenic mice presented a less pronounced decrease in myofiber size, lower protein levels of Foxo3a, and a spared increase in miRNA‐133b expression when compared with old wild‐type mice. Moreover, in BGP‐15‐treated old mice, the reduction in myofiber size was less intense, and the decline in muscle specific force was attenuated.
Conclusions
These results suggest that HSP70 overexpression attenuates sarcopenia in old mice, and this effect may be mediated by miR‐133b down‐regulation. In addition, BGP‐15 treatment may be a useful strategy to mitigate the effects of sarcopenia in old mice.
Objective:
We investigated changes in indices of muscle synergies prior to gait initiation and the effects of gaze shift in patients with Parkinson's disease (PD). A long-term objective of the study is to develop a method for quantitative assessment of gait-initiation problems in PD.
Methods:
PD patients without clinical signs of postural instability and two control groups (age-matched and young) performed a gait initiation task in a self-paced manner, with and without a quick prior gaze shift produced by turning the head. Muscle groups with parallel scaling of activation levels (muscle modes) were identified as factors in the muscle activation space. Synergy index stabilizing center of pressure trajectory in the anterior-posterior and medio-lateral directions (indices of stability) was quantified in the muscle mode space. A drop in the synergy index in preparation to gait initiation (anticipatory synergy adjustment, ASA) was quantified.
Results:
Compared to the control groups, PD patients showed significantly smaller synergy indices and ASA for both directions of the center of pressure shift. Both PD and age-matched controls, but not younger controls, showed detrimental effects of the prior gaze shift on the ASA indices.
Conclusions:
PD patients without clinically significant posture or gait disorders show impaired stability of the center of pressure and its diminished adjustment during gait initiation.
Significance:
The indices of stability and ASA may be useful to monitor pre-clinical gait disorders, and lower ASA may be relevant to emergence of freezing of gait in PD.
Age-related skeletal muscle atrophy appears to be a muscle group-specific process, yet only a few specific muscles have been investigated and our understanding in this area is limited. This review provides a comprehensive summary of the available information on age-related skeletal muscle atrophy in a muscle-specific manner, nearly half of which comes from the quadriceps. Decline in muscle-specific size over ~50yr of aging was determined from 47 cross-sectional studies of 982 young (~25yr) and 1,003 old (~75yr) individuals and nine muscle groups: elbow extensors (-20%, -0.39%/yr), elbow flexors (-19%, -0.38%/yr), paraspinals (-24%, -0.47%/yr), psoas (-29%, -0.58%/yr), hip adductors (-13%, -0.27%/yr), hamstrings (-19%, -0.39%/yr), quadriceps (-27%, -0.53%/yr), dorsiflexors (-9%, -0.19%/yr), and triceps surae (-14%, -0.28%/yr). Muscle-specific atrophy rate was also determined for each of the subcomponent muscles in the hamstrings, quadriceps, and triceps surae. Of all the muscles included in this review, there was more than a 5-fold difference between the least (-6%, -0.13%/yr, soleus) to the most (-33%, -0.66%/yr, rectus femoris) atrophying muscles. Muscle activity level, muscle fiber type, sex, and timeline of the aging process all appeared to have some influence on muscle-specific atrophy. Given the large range of muscle-specific atrophy and the large number of muscles that have not been investigated, more muscle-specific information could expand our understanding of functional deficits that develop with aging and help guide muscle-specific interventions to improve the quality of life of aging women and men.
Falls are the main contributor to both fatal and nonfatal injuries in elderly individuals as well as significant sources of morbidity and mortality, which are mostly induced by impaired balance control. The ability to keep balance is a remarkably complex process that allows for rapid and precise changes to prevent falls with multiple systems involved, such as musculoskeletal system, the central nervous system and sensory system. However, the exact pathogenesis of falls caused by balance disorders in the elderly has eluded researchers to date. In consideration of aging phenomenon aggravation and fall risks in the elderly, there is an urgent need to explore the pathogenesis and treatments of falls caused by balance disorders in the elderly. The present review discusses the epidemiology of falls in the elderly, potential pathogenic mechanisms underlying multiple systems involved in falls caused by balance disorders, including musculoskeletal system, the central nervous system and sensory system. Meanwhile, some common treatment strategies, such as physical exercise, new equipment based on artificial intelligence, pharmacologic treatments and fall prevention education are also reviewed. To fully understand the pathogenesis and treatment of falls caused by balance disorders, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies.
Muscle stem cells, also known as satellite cells, are responsible for the regenerative capacity of adult muscle tissue in response to stress and injury. Upon regenerative stimuli, satellite cells are activated and undergo myogenic commitment. Myogenic progenitors, which are termed myoblasts, undergo rapid proliferation, propagation, and differentiation into myocytes, which then fuse with each other to form new myotubes or to a pre-existing myotube. This process of myogenic differentiation is metabolically demanding and involves cellular remodeling of organelles and cellular architecture. Autophagy, a catabolic mechanism involving the sequestration of cellular contents into double membrane autophagosome vesicles, is strongly implicated at various stages during myogenesis; from the satellite stem cell to the mature muscle tissue. Moreover, aberrant autophagy (both the overstimulation and inhibition of autophagy) in both satellite cells and mature muscle cells can be detrimental for muscle health and physiology. This chapter outlines the importance of autophagy in maintaining skeletal muscle tissue homeostasis and satellite cell regenerative capacity.KeywordsAutophagyMuscle stem cellMyoblastMyogenesisSatellite cellSkeletal muscle
This study aimed to examine the reproducibility and validity of sitting Strength of the Muscles in Hip Abduction with Flexion (SMHAF) in young healthy adults. A total of 34 young healthy adults (15 men and 19 women) were included in the study. The reproducibility of sitting SMHAF was examined by determining the value of the intraclass correlation coefficient using the test–retest method. The validity of seated SMHAF was investigated by obtaining correlations between sitting SMHAF, supine SMHAF, and quadriceps muscle strength for both men and women. The reproducibility of the seated SMHAF was extremely high, with an intraclass correlation coefficient of 0.98. In both men and women, significant correlations as indices of lower limb muscle strength (p<0.05) were found between supine SMHAF and quadriceps muscle strength. These results indicate that seated SMHAF may be a reproducible and valid indicator of lower limb muscle strength in young healthy adults.
Malnutrition is one of the most common geriatric syndromes, and patients in the intensive care unit (ICU) are particularly exposed to a degradation of their nutritional status.
By completing this chapter, the reader will be able to:
Recognize and define the subject group of interest in the context of this book.
Identify the individual roles caregivers fulfill.
Relate the concept of caregiver burden to caregiving activities including post-intensive care syndrome (PICS-F).
Describe individual consequences and effects of caregiving activities on the caregiver.
Describe coping and support strategies that may be adopted to overcome negative aspects of caregiving.
KeywordsCaregiverCarerCaretakerRelativesFamily members
Finite element models of the head and neck are widely used in automotive and clinical fields to understand spinal biomechanics. These models are developed based on CT and MRI scans of the subjects, but historically the muscle data are obtained from cadaveric specimen. The cadaver data is often obtained from older specimens which commonly have undergone degenerative changes resulting in reduction in muscle cross section area. The objective of the current study is to compare the muscle cross-section area used by various finite element models of neck muscles used in the literature and to develop a normalization technique to scale the MRI muscle cross-section area with those available in the literature. Four male and seven female healthy asymptomatic young adult volunteers enrolled in the study after obtaining necessary approval from Institutional Review Board. T1 and T2 weighted magnetic resonance imaging was performed in neutral upright sitting position wearing military helmet. Muscle cross sectional area was obtained for multifidus muscles from the MRI images. Data was compared with those in the literature. Based on the literature review of prior studies, the cross-sectional area of cadaver specimens was smaller than the MRI obtained muscle area. Multifidus muscle scaling factor was obtained by ratio of sum of MRI cross section area with that of cadaver data. Based on the analysis, the scaling factor for male data is 1.6 and for female data is 1.3. the cadaver data can be multiplied by the scaling factor to obtain the MRI specific cross-sectional area.
A Normalization technique was developed for scaling MRI data into finite element model. This technique can be used in developing subject specific finite element model of spine which has applications in clinical, automotive, and military environment.
Background: Existing literature suggests exercise has variable efficacy on gains in physiological performance which translate to improved functional outcomes. Methods: We analysed the Graded Resistance Exercise And Type 2 Diabetes in Older adults (GREAT2DO) participants to explore links between health status, physical characteristics, and functional performance outcomes. Then compared high-intensity power training (PT) vs. SHAM low intensity exercises analysing changes in muscle function and then the changes in functional performance associated with changes in muscle function. Lastly, we identified genetic contributants to functional performance before and after physical activity in older adults. Results: Muscle function, body composition and neuropsychological status, were significantly associated with the variance functional performance outcomes. Twelve months of PT resulted in significantly greater increases in muscle strength, peak power, and endurance total work, compared to the SHAM group. Surprisingly, no effect of group assignment on any changes over time nor any relationships between changes in strength or power and changes in any functional outcomes except for chest press power and static balance changes across both groups. A portion of this heterogeneity may be due to variations in genetic profile, ACE (D) allele, ACTN3 (RR) genotype, UCP2 (GG) genotype, IL6-174 (GG), TNFα-308 (GG) and IL10-1082 (GG) genotype all predicted significantly superior PPTs and self-reported physical function after prescribed exercise or in those with higher levels of PA. Conclusion: This should help design future exercise interventions, which may be needed to enhance adaptations. Our power training intervention significantly improved muscle function, this did not translate to functional benefits. Further research is needed to define optimal lifestyle approaches, identify those with genetic profiles predicting attenuated adaptation who may require individualised exercise prescriptions.
Frailty of the locomotory organs has become a widespread problem in the geriatric population. The major factor leading to frailty is an age-associated decrease in muscular mass and a reduced number of muscular cells and myofibers.
In aged muscular tissues, muscular satellite cells (MuSCs) are reduced due to abnormalities in their self-renewal and the induction of apoptosis. However, the molecular mechanisms connecting aging-associated physiological changes and the reduction of MuSCs are largely unknown.
NIMA-related kinase 2 (Nek2), a member of the Nek family of serine/threonine kinases, was found to be downregulated in aged MuSCs/progenitors. Further, Nek2 downregulation was found to inhibit self-renewal and apoptotic cell death by activating the p53-dependent checkpoint. Attenuated NEK2 expression was also observed in the muscular tissues of elderly donors, and its function was confirmed to be conserved in humans.
Overall, this study proposes a novel mechanism for inducing muscular atrophy to understand aging-associated muscular diseases.
Lower-body power measured by a linear position transducer during the sit-to-stand (STS) movement declines with age and may be a predictor of physical disability in older adults. The purpose of this study was to establish normative data for STS power across the lifespan and to determine if differences exist between age cohorts, sexes, and age cohort–sex subgroups. Adults ( N = 557) aged 18–89 were divided into five age cohorts and performed the STS connected to a linear position transducer, which calculated power and velocity during the movement. Significantly lower ( p < .01) velocity was observed in a younger age cohort in females than males, whereas males saw a significant average power decrement ( p < .01) in a younger age cohort than females. STS power norms give clinicians a metric predicting physical disability and may be of particular interest to males as their power production begins to decline at an earlier age.
Zielstellung der Arbeit ist die Weiterentwicklung urbaner Räume mittels intelligenter Informationstechnologien, um das Leben in der Stadt zu verbessern. Hierbei gilt ein besonderes Interesse der Inklusion von Menschen mit körperlichen Beeinträchtigungen. Eine bedeutende Gruppe ist dabei die Menge hochbetagter Bürger. Die angestrebte Weiterentwicklung zielt darauf ab, dass bis ins hohe Alter selbstbestimmte Teilhabe am städtischen Leben und somit am Leben in der Gesellschaft möglich sein soll. Denn Teilhabe am Leben in der Gesellschaft konkretisiert sich wesentlich an der selbstbestimmten Ausübung außerhäuslicher Aktivitäten. Motorische Beeinträchtigungen im Altersgang führen allerdings zu einer signifikant wahrgenommenen Abnahme der Sicherheit (Safety) im urbanen Raum und dazu, dass betroffene Menschen Angst haben, den außerhäuslichen urbanen Raum zu benutzen. Um der daraus folgenden Meidung des außerhäuslichen urbanen Raumes entgegenzuwirken, verfolgt die Arbeit den Ansatz städtebauliche Objekte mittels Technologien des Internets of Things zu neuartigen sogenannten Smarten Städtebaulichen Objekten zu transformieren, die aktive Unterstützung für außerhäusliche Aktivitäten leisten. Smarte Städtebauliche Objekte sind mit Sensorik, Aktuatorik und Informationsverarbeitungskapazitäten ausgestattet und fähig, sich an individuelle Erfordernisse von Passanten zu adaptieren. Aufgrund altentypischer motorischer Beeinträchtigungen bestehen beispielsweise besondere Erfordernisse für Sitzgelegenheiten. Neben der informationstechnologischen Transformation einzelner städtebaulicher Objekte bestehen im urbanen Raum darüber hinaus wichtige Anforderungen an smarte städtebauliche Objektverbünde. Mittels einer intelligent koordinierten, gezielten Zurverfügungstellung der unterstützenden Funktionalitäten einzelner Smarter Städtebaulicher Objekte wird der urbane Raum als Gesamtsystem zu Adaptivität an Passantenerfordernisse ertüchtigt. Die Arbeit eruiert die Konzeption für eine adaptive Stadt mit einem Safety-Engineering-Ansatz am Beispiel smarter Sitzgelegenheiten und entwickelt ein Verfahren zur intelligenten Koordination für den smarten städtebaulichen Objektverbund. Für eine erfordernisgenaue Allokation einzelner smarter Sitzgelegenheiten als öffentliche Objekte wird dazu ein Wohlfahrtskalkül zugrunde gelegt, welches in dem Sinne gerecht sein soll, dass eine Übervorteilung einzelner Passanten vermieden wird. Mithilfe von Methoden der Künstlichen Intelligenz entwickelt die Arbeit ein heuristisches Verfahren für die Suche nach einer Lösung gemäß des Wohlfahrtskalküls. Dies implementiert dem Wohlfahrtskalkül zugrundeliegende Aspekte der Theorie der Gerechtigkeit nach John Rawls für das Beispiel des urbanen Raums. Eine szenariobasierte Simulation weist nach, dass der entwickelte Lösungsansatz die Safety-orientierte Wohlfahrt im urbanen Raum effektiv erhöhen kann.
Although previous studies have highlighted the association between physical activity and lower extremity function (LEF) in elderly individuals, the mechanisms underlying this relationship remain debated. Our recent work has recognized the utility of nonlinear trimodal regression analysis (NTRA) parameters in characterizing changes in soft tissue radiodensity as a quantitative construct for sarcopenia in the longitudinal, population-based cohort of the AGES-Reykjavík study. For the present work, we assembled a series of prospective multivariate regression models to interrogate whether NTRA parameters mediate the 5-year longitudinal relationship between physical activity and LEF in AGES-Reykjavík participants. Healthy elderly volunteers from the AGES-Reykjavík cohort underwent mid-thigh X-ray CT scans along with a four-part battery of LEF tasks: normal gait speed, fastest-comfortable gait speed, isometric leg strength, and timed up-and-go. These data were recorded at two study timepoints which were separated by approximately 5 years: AGES-I (n = 3157) and AGES-II (n = 3098). Participants in AGES-I were likewise administered a survey to approximate their weekly frequency of engaging in moderate-to-vigorous physical activity (PAAGES-I). Using a multivariate mediation analysis framework, linear regression models were assembled to test whether NTRA parameters mediated the longitudinal relationship between PAAGES-I and LEFAGES-II; all models were covariate-adjusted for age, sex, BMI, and baseline LEF, and results were corrected for multiple statistical comparisons. Our first series of models confirmed that all four LEF tasks were significantly related to PAAGES-I; next, modelling the relationship between PAAGES-I and NTRAAGES-II identified muscle amplitude (Nm) and location (μm) as potential mediators of LEF to test. Finally, adding these two parameters into our PAAGES-I → LEFAGES-II models attenuated the prior effect of PAAGES-I; bootstrapping confirmed Nm and μm as significant partial mediators of the PAAGES-I → LEFAGES-II relationship, with the strongest effect found in isometric leg strength. This work describes a novel approach toward clarifying the mechanisms that underly the relationship between physical activity and LEF in aging individuals. Identifying Nm and μm as significant partial mediators of this relationship provides strong evidence that physical activity protects aging mobility through the preservation of both lean tissue quantity and quality.
Varios investigadores creen que los factores que coadyuvan al envejecimiento pueden ser primarios (genética) o también secundarios (ejercicio, nutrición, lesiones y trastornos patológicos. Es por ese motivo que los adultos mayores manifiestan alteraciones del control reactivo, junto a retrasos de las diferentes respuestas musculares por lo que requieren aún más tiempo para restablecer su equilibrio. Además, existe un retraso en la activación de las respuestas posturales en el control del equilibrio proactivo, lo que produce una inestabilidad mayor para poder realizar las actividades de la vida cotidiana (levantarse, subir y bajar gradas, etc.). Varios sistemas que se incluyen dentro del equilibrio, control postural y motor se ven afectados al pasar los años, al igual que la misma hipotrofia muscular que comienza a partir de los 30 años si es que el individuo es sedentario; así como las fibras musculares de tipo I (oxidativa lenta, utilizada en actividades como control postural), que según varios estudios demostraron existe una pérdida de este tipo de fibras musculares relacionadas con la edad; de manera específica, describiendo a los factores que puedan contribuir al envejecimiento y sus complicaciones en la rehabilitación en adultos mayores tomando en cuenta los cambios relacionados con la vejez y la alteración del control postural.
Calpain activation has been postulated as a potential contributor to the loss of muscle mass and function associated with both aging and disease but limitations of previous experimental approaches have failed to completely examine this issue. We hypothesized that mice overexpressing calpastatin, an endogenous inhibitor of calpain (CalpOX), solely in skeletal muscle would show an amelioration of the aging muscle phenotype. We assessed 4 groups of mice (age in months): (1) young wild type (5.71±0.43) (WT); (2) young CalpOX (5.6±0.5); (3) old WT (25.81±0.56); and (4) old CalpOX (25.91±0.60) for diaphragm and limb muscle (extensor digitorum longus, EDL) force frequency relations. Aging significantly reduced diaphragm and EDL peak force in old WT mice, and decreased the force-time integral during a fatiguing protocol by 48% and 23% in aged WT diaphragm and EDL, respectively. In contrast, we found that CalpOX mice had significantly increased diaphragm and EDL peak force in old mice, similar to that observed in young mice. The impact of aging on the force-time integral during a fatiguing protocol was abolished in the diaphragm and EDL of old CalpOX animals. Surprisingly, we found that CalpOX had a significant impact on longevity, increasing median survival from 20.55 months in WT mice to 24 months in CalpOX mice (p = 0.0006).
Understanding the hip loading environment for daily activities is useful for hip fracture prevention, rehabilitation, and the design of osteogenic exercises. Seventeen older adults (50–70 yrs) and twenty young adults (18–30 yrs) were recruited. A rigid body model combined with a musculoskeletal model was used to estimate lower extremity loading. An elliptical cross-section model of the femoral neck was used to estimate femoral neck stress during stair ascent and descent. Two peaks were identified in the stress curves, corresponding to the peaks in the vertical ground reaction force. During stair ascent, significantly higher tension on the superior femoral neck was found for the young group at peak 1 (young: 13.5±6.1 MPa, older: 4.2±6.5 MPa, p<0.001). Also during stair ascent, significantly higher compression on the posterior femoral neck was found for the older group at peak 2 (young: -11.4±4.9 MPa, old: -18.1±8.6 MPa, p = 0.006). No significant difference was found for stair descent. Components of stress (muscle vs. reaction forces; axial forces vs. bending moments) were also examined for each trial of stair ascent and descent. The stresses and their components provided loading magnitude and locations of higher stress on the femoral neck during stair ascent and descent. Understanding femoral neck stresses may be used to help prevent hip fractures, reduce pain, improve rehabilitation, and design osteogenic exercises.
AUT00063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K+ channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on auditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic startle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug administration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT00063 and AUT00202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT00063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT00063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT00063 and AUT00202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.
Sarcopenia is attracting attention today because it is associated with life prognosis, but the definition of sarcopenia has not been established. Until now, muscle mass reduction was considered an indispensable element of sarcopenia, but in 2019 EWGSOP announced that sarcopenia must firstly involve reduced muscle strength, adding that both muscle mass and muscle quality are important. We must also recognize the differences between disuse syndrome and sarcopenia. Although increasing reports are emerging of dysphagia due to sarcopenia, it is important to understand that general muscle sarcopenia and sarcopenia of swallowing muscles are different. The muscle related to swallowing is the striated muscle, but it is embryologically close to the respiratory muscle derived from the branchial arch and has characteristics different from those of the limb skeletal muscles. The swallowing muscle is difficult to become disused because it is driven by respiratory input at rest. The only exception is the geniohyoid muscle, which is prone to sarcopenia. While it is important to understand the dysphagia caused by sarcopenia of the swallowing muscles, many diseases that cause dysphagia in the elderly are complicated with sarcopenia, complicating the pathophysiology.
To clarify the clinical usefulness of the strength of the muscles involved in hip abduction with flexion, the influences of knee pain on such strength and that of the quadriceps femoris were examined, involving 227 community-dwelling elderly females divided into 2 groups with (45) and without (182) knee pain. For both groups, the strengths of the muscles involved in hip abduction with flexion and quadriceps femoris, toe and hand grip strengths, number of sit-ups, CS-30, TUG, and 5MWT scores, and body composition (muscle mass, skeletal muscle mass, and lower limb muscle mass) were measured. The strength of the muscles involved in hip abduction with flexion was significantly correlated with all physical function parameters in both groups. The quadriceps femoris muscle strength was significantly correlated with all physical function parameters in the group without knee pain, but it was not significantly correlated with TUG or 5MWT scores in the group with it. The results suggest that the strength of the muscles involved in hip abduction with flexion is more useful than that of the quadriceps femoris to assess the dynamic standing balance and walking abilities of elderly people with knee pain.
To clarify simple methods to assess community-dwelling elderly femalesʼlower extremity functions, 154 elderly females leading an independent life in communities were assessed using the 30-second Chair Stand Test (CS-30) and 10-second Chair Stand Test for the Frail Elderly (Frail CS-10), and the correlations between scores from these tests and the upper/lower limb and trunk muscle strength, flexibility, and static/dynamic standing balance were analyzed. Multiple regression analysis revealed that both CS-30 and Frail CS -10 scores are correlated independently with 3 parameters: the quadriceps femoris muscle strength, number of sit-ups, and TUG score. The results support the usefulness of CS-30 and Frail CS-10 as simple and convenient scales not requiring special devices to assess community-dwelling elderly femalesʼlower limb muscle strength and dynamic balance. Frail CS-10 was suggested to be particularly useful as a method to simply assess the lower extremity functions of such females, including those leading an independent life.
New findings:
What is the central question of this study? Estradiol (E2 ) plays an important role in regulating skeletal muscle strength in females. Here, we asked to what extent E2 deficiency affects recovery of strength and satellite cell number when muscle is challenged by multiple injuries. What is the main finding and its importance? E2 deficiency impairs the adaptive potential of skeletal muscle following repeated injuries, as measured by muscle mass and strength. The impairment is likely multifactorial with our data indicating that one mechanism is reduction in satellite cell number. Our findings have implications for aging, hormone replacement and regenerative medicine in regards to maintaining satellite cell number and ultimately the preservation of skeletal muscle's adaptive potential.
Abstract:
Estradiol effects on skeletal muscle are multifactorial including the preservation of mass, contractility and regeneration. Here, we aimed to determine the extent to which estradiol deficiency affects strength recovery when muscle is challenged by multiple BaCl2 -induced injuries and to assess how satellite cell number is influenced by the combination of estradiol deficiency and repetitive skeletal muscle injuries. A longitudinal study was designed, using an in vivo anesthetized mouse approach to precisely and repeatedly measure maximal isometric torque, coupled with endpoint fluorescent-activated cell sorting to quantify satellite cells. Isometric torque and strength gains were lower in ovariectomized mice at several time points after the injuries compared to those treated with 17β-estradiol. Satellite cell number was 41-43% lower in placebo- than estradiol-treated ovariectomized mice, regardless of injury status or number of injuries. Together, these results indicate that the loss of estradiol blunts adaptive strength gains and that the number of satellite cells likely contributes to the impairment. This article is protected by copyright. All rights reserved.
Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the “Skeletal Muscle Physiology” presentation located on the American Physiological Society Archive of Teaching Resources Web site ( http://www.apsarchive.org ).
The present study investigated the effects of aging on the contractile properties of the adult diaphragm in 42 Golden Syrian hamsters. Experiments were performed on isolated diaphragm strips from three groups of animals 4.9 +/- 0.4 (SE), 12.8 +/- 0.2, and 18.8 +/- 0.3 months of age. Aging was associated with a decrease in the maximal isometric tension generated per unit cross-sectional area of muscle and slowing in the time-to-peak tension and rate of muscle relaxation. The velocity of muscle shortening at a given load was also significantly less in older than in younger animals, and the force-velocity curve became flatter with advancing age as reflected by increases in the Hill coefficient (a/P0). Changes in maximal active tension and maximal velocity of unloaded shortening with aging correlated weakly (r greater than 0.3; p less than 0.05) and were of similar magnitude (-17 to -21%), suggesting that aging affects these two indices of muscle function in similar fashion. Finally, the diaphragm fatigued more rapidly in older than in younger animals. We conclude that aging depresses the ability of the adult diaphragm to generate tension and to shorten and resist fatigue.
1. Cat soleus (slow twitch) was cross‐reinnervated with nerve to flexor hallucis or digitorum longus muscle (fast twitch). More than 3 years later motor unit isometric contractions and muscle immunohistochemistry and histochemistry were investigated. All muscles differed from normal fast or slow muscle.
2. The motor units could be divided into two groups: one with fast twitches and low tetanic tension, the other with slow twitches and high tension. This is the reverse of the relation between motor unit twitch time and tetanic tension in normal muscle (fast or slow).
3. Motor unit twitch time to peak decreased with axonal conduction velocity, as in normal muscle, but so did tetanic tension, which is abnormal.
4. Twitch—tetanus ratio increased with twitch time to peak in the group of slow units but not in the fast group (although the range of ratios was as great).
5. A tetanus depressed the twitch tension of slow motor units and potentiated fast ones as in normal muscle but the potentiation was often accompanied by an abnormal prolongation of the twitch.
6. The mean conduction velocity of axons was slightly higher than at 6 months' reinnervation but below the normal value for fast muscle.
7. Antibody to slow myosin was bound strongly to Type I fibres but not to Type II fibres, confirming the histochemical division of fibres into Types I and II.
8. More than 95% of the fibres were oxidative, with Type I predominating over Type II a in the ratio of about 2:1.
9. The higher tension of the slow motor units was the result of three factors: the number of fibres per motor unit was at least three times that in the fast; Type I fibres had cross‐sectional areas little less than Type II (a and b together) and were estimated to develop more tension per unit area. All three findings were different from those in normal fast muscle.
10. One flexor hallucis longus muscle was self‐reinnervated and examined histochemically. This muscle was abnormal in that a large majority of the fibres were Type I.
Metabolite concentrations of adenosine-5'-phosphate, phosphocreatine, and lactate were compared in adult and aged rat soleus and superficial, medial and deep, lateral gastrocnemius muscles after 3 min of moderate or intense stimulation in situ. The concentration of phosphocreatine in all muscles progressively decreased as contractile frequency increased. In most muscles, lactate increased coincident with greater contractile frequency. These changes were greater in aged muscles. Decreases in the concentration of adenosine-5'-phosphate with stimulation, where evident, were also greater in aged muscles. Metabolite levels in nonstimulated muscles were effected minimally by age. The cytochrome-c concentration was reduced with age in each muscle section. The results indicate that aged skeletal muscle has a lesser ability than adult skeletal muscle to maintain energy balance during contraction.
Twelve men and twelve women 78-81 years of age were studied with muscle biopsies from the right vastus lateralis and biceps brachii and with measurements of isometric and isokinetic strength for knee-extention and isometric strength for elbow-flexion. Bicycle ergometry with determination of heart rate and oxygen uptake at submaximal (50 W) and "maximal" work loads was also performed. Body cell mass was estimated from measurements of total body potassium. Muscle fibre composition with respect to slow twitch (ST = type I) and fast twitch (FT = type II) fibres did not differ between the sexes and the younger subjects drawn from population studies. The mean fibre areas averaged in vastus lateralis 4.7 and 3.3 micrometers 2 X 10(3) in men and women, respectively. This is less than 10 up to 30% of values found in sedentary younger subjects. The decline dominated in FT fibres, especially FTb fibres. In contrast biceps brachii did not show any matched fibre size reduction. The number of atrophic fibres was high and so was the frequency of "enclosed" fibres and areas with type grouping (ST fibres), indicating denervation--reinnervation. Such abnormalities are rarely seen in younger ages. Correlation analysis showed that only a minor part of the reduction in body cell mass with age could be explained by a reduction in fibre areas and that a reduction with age of the number of muscle fibres of both fibre types must be assumed. Positive correlations were observed between muscle strength and mean fibre and FT fibre areas. Comparing the present findings of skeletal muscle morphology to those in younger age groups, it is apparent that during the 8th decade of life major changes do occur. The measurements of aerobic and anaerobic enzymatic activities and of muscle capillary supply showed that levels comparable to those of younger age groups are maintained. Thus, quantitative rather than qualitative changes may explain the reduction in work performance with age.
Age trends in record running performances, over distances from 100 yards to the marathon, were analyzed for males between 40-74 years. Within event distances, an exponential model most accurately related performance time to age. In terms of this model, rate of age decline in running performance was greater for middle and longer distance events than for sprints. Within age-levels, linear and power models were highly accurate in relating performance time to event distance. A general model, that proved highly accurate in accounting for variance in performance times over the full age and distance ranges, expressed performance as the product of a power function of distance and an exponential function of age. Findings are discussed in terms of anaerobic and aerobic processes that underlie running performance at different event distances.