Brian C. Clark

Functional consequences of sarcopenia and dynapenia in the elderly.

Purpose of reviewThe economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article, we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed. Recent findingsRecent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia. SummaryAlthough muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood and further research is needed to better elucidate these mechanisms between muscle groups and across populations.

Blood flow restricted exercise and skeletal muscle health.

For nearly half a century, high mechanical loading and mechanotransduction pathways have guided exercise recommendations for inducing muscle hypertrophy. However, emerging research on low-intensity exercise with blood flow restriction challenges this paradigm. This article will describe the BFR exercise model and discuss its efficacy, potential mechanisms, and clinical viability.

What is dynapenia

Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by neurologic or muscular diseases. Dynapenia predisposes older adults to an increased risk for functional limitations and mortality. For the past several decades, the literature has largely focused on muscle size as the primary cause of dynapenia; however, recent findings have clearly demonstrated that muscle size plays a relatively minor role. Conversely, subclinical deficits in the structure and function of the nervous system and/or impairments in the intrinsic force-generating properties of skeletal muscle are potential antecedents to dynapenia. This review highlights in the contributors to dynapenia and the etiology and risk factors that predispose individuals to dynapenia. In addition, we address the role of nutrition in the muscular and neurologic systems for the preservation of muscle strength throughout the life span.

Older adults exhibit more intracortical inhibition and less intracortical facilitation than young adults.

BACKGROUND Aging results in decreased neuromuscular function, which is likely associated with neurologic alterations. At present little is known regarding age-related changes in intracortical properties. METHODS In this study we used transcranial magnetic stimulation (TMS) to measure intracortical facilitation (ICF), short- and long-interval intracortical inhibition (SICI and LICI), motor evoked potential amplitude, and silent period duration in young and older adults (21.4+/-0.8years and 70.9+/-1.8years). These variables were assessed from the flexor carpi radialis muscle of the non-dominant arm under resting conditions, and during a submaximal contraction (intensity 15% maximum strength). RESULTS Older adults exhibited increased SICI and LICI in comparison to young adults (SICI: 29.0+/-9.2% vs. 46.2+/-4.8% of unconditioned pulse; LICI: 6.5+/-1.7% vs. 15.8+/-3.3% of unconditioned pulse; P=0.04), and less ICF under resting conditions (74.6+/-8.7% vs. 104.9+/-6.9% of unconditioned pulse; P=0.02). These age-related differences disappeared during contraction, although the older adults did exhibit a longer silent period during contraction (112.5+/-6.5 vs. 84.0+/-3.9ms; P<0.01). CONCLUSIONS Collectively, these findings suggest increased GABA mediated intracortical inhibition with age.

Relative safety of 4 weeks of blood flow‐restricted resistance exercise in young, healthy adults

This study evaluated the effect of 4 weeks of low‐load resistance exercise with blood flow restriction (BFRE) on increasing strength in comparison with high‐load resistance exercise (HLE), and assessed changes in blood, vascular and neural function. Healthy adults performed leg extension BFRE or HLE 3 days/week at 30% and 80% of strength, respectively. During BFRE, a cuff on the upper leg was inflated to 30% above systolic blood pressure. Strength, pulse‐wave velocity (PWV), ankle‐brachial index (ABI), prothrombin time (PT) and nerve conduction (NC) were measured before and after training. Markers of coagulation (fibrinogen and D‐dimer), fibrinolysis [tissue plasminogen activator (tPA)] and inflammation [high sensitivity C‐reactive protein (hsCRP)] were measured in response to the first and last exercise bouts. Strength increased 8% with BFRE and 13% with HLE (P<0.01). No changes in PWV, ABI, PT or NC were observed following training for either group (P>0.05). tPA antigen increased 30–40% immediately following acute bouts of BFRE and HLE (P=0.01). No changes were observed in fibrinogen, D‐dimer or hsCRP (P>0.05). These findings indicate that both protocols increase the strength without altering nerve or vascular function, and that a single bout of both protocols increases fibrinolytic activity without altering selected markers of coagulation or inflammation in healthy individuals.

Age-Related Changes in Motor Cortical Properties and Voluntary Activation of Skeletal Muscle

Aging is associated with dramatic reductions in muscle strength and motor control, and many of these agerelated changes in muscle function result from adaptations in the central nervous system. Aging is associated with widespread qualitative and quantitative changes of the motor cortex. For example, advancing age has been suggested to result in cortical atrophy, reduced cortical excitability, reduced cortical plasticity, as well as neurochemical abnormalities.The associated functional effects of these changes likely influence numerous aspects of muscle performance such as muscle strength and motor control. For example, there is evidence to suggest that the muscle weakness associated with aging is partially due to impairments in the nervous systems ability to fully activate motor neurons- particularly in the larger proximal muscle groups. In this review article we discuss age-related changes in the motor cortex, as well as the abilityor lack thereof- of older adults to voluntarily activate skeletal muscle. We also provide perspectives on scientific and clinical questions that need to be addressed in the near future.

Myogenic and proteolytic mRNA expression following blood flow restricted exercise.

Aim:  Resistance exercise performed at low loads (20–30% of maximal strength) with blood flow restriction (BFR) acutely increases protein synthesis and induces hypertrophy when performed chronically. We investigated myogenic and proteolytic mRNA expression 8 h following an acute bout of knee extension exercise.

In vivo alterations in skeletal muscle form and function after disuse atrophy.

Prolonged reductions in muscle activity and mechanical loading (e.g., bed rest, cast immobilization) result in alterations in skeletal muscle form and function. The purpose of this review article was to synthesize recent findings from several studies on the dramatic effects of disuse on skeletal muscle morphology and muscle performance in humans. Specifically, the following are discussed: 1) how the antigravity muscles are most susceptible to atrophy and how the degree of atrophy varies between muscle groups; 2) how disuse alters muscle composition by increasing intermuscular adipose tissue; 3) the influence of different disuse models on regulating the loss of muscle mass and strength, with immobilization causing greater reductions than bed rest and limb suspension do; 4) the observation that disuse decreases strength to a greater extent than muscle mass and the role of adaptations in both neural and contractile properties that influences this excessive loss of strength; 5) the equivocal findings on the effect of disuse on muscle fatigue resistance; and 6) the reduction in motor control after prolonged disuse. Lastly, emerging data warranting further inquiry into the modulating role of biological sex on disuse-induced adaptations are also discussed.

Derecruitment of the lumbar musculature with fatiguing trunk extension exercise.

Study Design. This was a descriptive study involving 20 healthy individuals. Objectives. To evaluate the neuromuscular activation patterns of the lumbar paraspinal and hip extensor muscles during isotonic trunk extension exercise. Summary of Background Data. Few studies have evaluated the effect of muscle fatigue on the lumbar musculature during isotonic exercise. Methods. Electromyographic activity was recorded continuously from the lumbar paraspinal, gluteus maximus, and biceps femoris muscles during isotonic trunk extension exercise performed to muscular failure. Root mean squared electromyography was determined over the concentric portion of each repetition, and polynomial regression analysis was used to describe the association between fatigue and the recruitment patterns. Results. The lumbar paraspinals demonstrated an increase in the electromyogram signal up to 57.9% of maximal fatigue, at which point decrements in electromyography were observed (lumbar [quadratic curve] R2 = 0.0807, SEE = 0.228; &bgr;2 = −8.245−5) (P < 0.000). Associated with fatigue, the gluteus maximus demonstrated an increase in electromyography, with an exponential breakpoint occurring at 35.9% of maximal fatigue (gluteus maximus [quadratic curve]: R2 = 0.5059, SEE = 0.865; &bgr;2 = 0.00017) (P = 0.014). The biceps femoris demonstrated a linear increase in electromyography with fatigue (R2 = 0.4667, SEE = 0.284; &bgr; = 0.0091) (P < 0.000). To further investigate the derecruitment of the lumbar extensors associated with fatigue, study participants were analyzed individually with regression analyses. Results revealed that the majority of study participants (68.5%) demonstrated a significant decrease (quadratic bend) in lumbar electromyography, with decrements in muscle activity beginning at 53% of maximum. Conclusion. During fatiguing trunk extension exercise, an increase in the lumbar paraspinal electromyogram signal occurs up to approximately 55% of maximum fatigue, at which point a decrease in electromyography is observed. Associated with this derecruitment is a concomitant increase in hip extensor muscle activity, suggesting that as the lumbar musculature becomes fatigued, these muscles allow for continuation of the exercise.

Aging and muscle: a neuron’s perspective

Purpose of reviewAge-related muscle weakness causes a staggering economic, public, and personal burden. Most research has focused on internal muscular mechanisms as the root cause to strength loss. Here, we briefly discuss age-related impairments in the brain and peripheral nerve structures that may theoretically lead to muscle weakness in old age. Recent findingsNeuronal atrophy in the brain is accompanied by electrical noise tied to declines in dopaminergic neurotransmission that degrades communication between neurons. Additionally, sensorimotor feedback loops that help regulate corticospinal excitability are impaired. In the periphery, there is evidence for motor unit loss, axonal atrophy, demyelination caused by oxidative damage to proteins and lipids, and modified transmission of the electrical signal through the neuromuscular junction. SummaryRecent evidence clearly indicates that muscle weakness associated with aging is not entirely explained by classically postulated atrophy of muscle. In this issue, which focuses on ‘Ageing: Biology and Nutrition’ we will highlight new findings on how nervous system changes contribute to the aging muscle phenotype. These findings indicate that the ability to communicate neural activity to skeletal muscle is impaired with advancing age, which raises the question of whether many of these age-related neurological changes are mechanistically linked to impaired performance of human skeletal muscle. Collectively, this work suggests that future research should explore the direct link of these ’upstream’ neurological adaptions and onset of muscle weakness in elders. In the long term, this new focus might lead to novel strategies to attenuate the age-related loss of muscle strength.