Regulation of skeletal muscle capillarization involves distinct signaling pathways and growth factors including nitric oxide and vascular endothelial growth factor. Our understanding of this complex regulation continues to expand with the identification of new angiogenic growth factors. Future work needs to increase the use of advanced molecular techniques to expand our knowledge of the regulation of basal and exercise-induced capillarization.
capillaries; exercise; mitochondria; muscle fiber size; VEGF; nitric oxide; 5′-AMP activated protein kinase
This review presents the hypothesis that muscle is a source of secreted factors (myokines) that can influence bone mass in both positive and negative ways. Growth factor secretion by muscle may therefore be one pathway through which mechanical signals are transduced biologically.
IGF-1; FGF-2; Myostatin; periosteum; muscle injury
Severe obesity is increasing at a disproportionate rate compared to milder grade obesity. Our research group has obtained evidence indicative of an “obesity metabolic program” in the skeletal muscle of severely obese individuals which may be genetically or epigenetically determined. We believe this represents a paradigm shift in thinking about metabolic regulation in obesity.
Bariatric surgery; Exercise training; Fat oxidation; Class III obesity; Insulin action; Mitochondria; Obesity
Statins are effective for reducing low-density lipoprotein cholesterol and cardiac events, but can produce muscle side effects. We have hypothesized that statin-related muscle complaints are exacerbated by exercise and influenced by factors including mitochondrial dysfunction, membrane disruption and/or calcium handling. The interaction between statins, exercise and muscle symptoms may be more effectively diagnosed and treated as rigorous scientific studies accumulate.
cholesterol-lowering medication; muscle strength; aerobic capacity; myalgia; Vitamin D; HMG CoA Reductase Inhibitor
Human exposure to cold stimulates cutaneous vasoconstriction by activating both sympathetic reflex and locally mediated pathways. Older humans are vulnerable to hypothermia because primary aging impairs thermoregulatory cutaneous vasoconstriction. This article highlights recent findings discussing how age-related decrements in sympathetic neurotransmission contribute directly to thermoregulatory impairment, whereas changes in local cold-induced intracellular signaling suggest a more generalized age-associated vascular dysfunction.
skin blood flow; aging; temperature regulation; adrenergic; Rho kinase; cold
Enhanced external counterpulsation (EECP) is a non-invasive treatment for coronary artery disease (CAD) patients who have angina pectoris that is refractory to pharmacotherapy and revascularization. The popular concept is that EECP may promote collateral development and improve myocardial perfusion. We hypothesize that improvements in peripheral arterial function are responsible for the clinical benefits of EECP.
angina pectoris; nitric oxide; endothelium; flow-mediated dilation; arterial stiffness
Mitochondria are dynamic organelles in skeletal muscle critical in physical performance and disease. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes, conferring positive impacts on skeletal muscle contractile and metabolic functions. This review focuses on the regulation of these processes by endurance exercise and discusses potential benefits in health and disease.
Skeletal muscle; exercise-induced adaptation; mitochondrial biogenesis; mitochondrial fission; mitochondrial fusion; autophagy; mitophagy
Questionnaires that assess active and sedentary behaviors in large-scale epidemiologic studies are known to contain substantial errors. We present three options for improving measures of physical activity behaviors in large-scale epidemiologic studies, discuss the problems and prospects for each of these options, and highlight a new direction for measuring these behaviors in such studies.
Exposure assessment; Exercise; Sitting; Measurement error; Disease prevention
Concussion has been viewed historically as a transient injury with no evidence supporting the existence of persistent effects. However, our recent work demonstrates electroencephalographic and motor control changes in otherwise healthy individuals with a history of concussion. We therefore hypothesize that concussive and subconcussive head impacts set about a cascade of pathological events that accelerates declines in cognitive function typically associated with the aging process.
Endogenous heat shock proteins (HSP) are decreased in disease states associated with insulin resistance and aging. Induction of HSPs has been shown to decrease oxidative stress, inhibit inflammatory pathways, and enhance metabolic characteristics in skeletal muscle. As such, HSPs have the potential to function as an important defense system against the development of insulin resistance and type 2 diabetes.
insulin signaling; glucose uptake; oxidative stress; stress kinases; mitochondria; aging; obesity
Older adults exhibit greater motor variability, which impairs their accuracy and function, compared with young adults. Low-intensity training that emphasizes muscle coordination reduces variability in older adults. Furthermore, low amount of visual feedback minimizes age-associated differences in variability. We hypothesize that an intervention that combines muscle coordination and reduced visual feedback would be advantageous to improve motor control in older adults.
neuromuscular control; force variability; movement control; aging; intervention; training
Total knee arthroplasty (TKA) is associated with persistent quadriceps dysfunction. Since quadriceps dysfunction impairs functional performance, minimizing quadriceps dysfunction by attenuating central activation deficits early after surgery may improve function later in life. Rehabilitation strategies incorporating neuromuscular electrical stimulation and early, aggressive quadriceps strengthening may prove beneficial. Further, surgical approaches such as minimally invasive TKA may minimize post-operative quadriceps dysfunction.
Strength; muscle inhibition; rehabilitation; neuromuscular electrical stimulation; joint replacement
Muscle power declines earlier and more precipitously with advancing age compared to muscle strength. Peak muscle power has also emerged as an important predictor of functional limitations in older adults. Our current working hypothesis is focused on examining lower extremity muscle power as a more discriminant variable for understanding the relationships between impairments, functional limitations and resultant disability with aging.
Aging; muscle power; exercise physiology; physical function; mobility-disability
Physical activities undertaken in childhood, particularly activities which apply large forces quickly convey optimal benefits to bone mass, size, and structure. Evidence is accumulating that benefits persist well beyond activity cessation. This review examines the potential for early childhood activity to improve bone mineralization and structure and explores childhood activity as prevention for osteoporosis in later life.
Osteoporosis; Bone mineral content; Bone strength; Weight-bearing physical activity; Puberty; Peak bone mass
This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research.
exercise genomics; candidate genes; single nucleotide polymorphism; genome-wide association study; genomic predictors
Even when adults meet physical activity guidelines, sitting for prolonged periods can compromise metabolic health. TV time and objective-measurement studies show deleterious associations, and breaking up sedentary time is beneficial. Sitting time, TV time, and time sitting in automobiles increase premature mortality risk. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required.
environmental and social change; TV time; breaks in sedentary time; accelerometer measurement; blood glucose; triglycerides; metabolic health
Mitochondrial dysfunction and oxidative stress are thought to play important roles in mammalian aging. Resveratrol is a plant-derived polyphenol that exerts diverse anti-aging activities, mimicking some of the molecular and functional effects of dietary restriction. This review focuses on the molecular mechanisms underlying the mitochondrial protective effects of resveratrol, which could be exploited for the prevention or amelioration of age-related diseases in the elderly.
senescence; bioenergetics; mitochondria; aging; caloric restriction; cardiovascular disease; phytochemicals; 3,5,4′-trihydroxystilbene
We have demonstrated in several studies that obesity and adipokines are more strongly associated with asthma in women than in men. The reason for this controversial sex difference is not known. Based on our prior studies, we hypothesize that sex-related difference in ectopic fat may explain the obesity-asthma association in women.
adipokine; leptin; adiponectin; physical activity; gonadal hormones; obesity
Whole-body heating decreases pulmonary capillary wedge pressure and cerebral vascular conductance, and causes an inotropic shift in the Frank-Starling curve. Whole-body cooling increases pulmonary capillary wedge pressure and cerebral vascular conductance without changing systolic function. These and other data indicate factors affecting cardiac function may mechanistically contribute to syncope during heat stress and improvements in orthostatic tolerance during cold stress.
hyperthermia; hypothermia; cardiac contractility; pressure-volume relations; orthostatic tolerance
The leading joint hypothesis (LJH) offers a novel interpretation of control of human movements that involve multiple joints. The LJH makes control of each multijoint movement transparent. This review highlights effective applications of the LJH to learning of new motor skills and to analysis of movement changes caused by aging and motor disorders.
arm movement; intersegmental dynamics; torque analysis; coordination; motor learning; motor disorder
Low-frequency fatigue (LFF) is characterized by a proportionally greater loss of force at low compared to high activation frequencies and a prolonged recovery. Recent work suggests a calcium-induced uncoupling of excitation-contraction coupling underlies LFF. Here newly characterized triadic proteins are described and possible mechanisms by which they may contribute to LFF are suggested.
Sarcoplasmic reticulum; Ryanodine receptor; Junctophilin; Mitsugumin; JFP-45; Calcium channels
A single bout of exercise can lead to a postexercise decrease in blood pressure in hypertensive individuals, called postexercise hypotension. Compelling evidence suggests that the central baroreflex pathway plays a crucial role in the development of postexercise hypotension. This review focuses on the exercise-induced changes in brainstem nuclei involved in blood pressure regulation.
baroreflex; brainstem; exercise; hypertension; neuroplasticity
Ghrelin and leptin, putative controllers of human appetite, have no effect on human meal-to-meal appetite but respond to variations in energy availability. Nonhomeostatic characteristics of appetite and spontaneous activity stem from inhibition by leptin and ghrelin of brain reward circuit that is responsive to energy deficit, but refractory in obesity, and from the operation of a meal-timing circadian clock.
Leptin; insulin; ghrelin; motivation; reward; obesity
This decadal perspective summarizes novel, insightful observations achieved in exercise science. The topics span genomics and gene function, epigenetics, cell signaling, epidemiological phenomena and other important areas. A future strategy is presented along two parallel, integrated paths involving: 1) a continuance of genomic discovery and gene function; 2) classical biochemical/ physiological approaches toward solving biological- and health/disease-related phenomena.
gene regulation; muscle as an endocrine organ; epigenetics; cell signaling; biochemistry; epidemiology; obesity
Muscle weakness ensues when serum testosterone declines with age in men. Testosterone’s female counterpart, estrogen, has also been implicated in age-related strength loss but these results are less conclusive. Our working hypothesis is that estrogens do benefit muscle strength, and that the underlying mechanism involves estrogen receptors to improve muscle quality more so than quantity.
aging; skeletal muscle; hormone replacement therapy; 17β-estradiol; myosin; estrogen receptor