scholarly journals Skeletal Muscle Mitochondrial Physiology in Children With Cerebral Palsy: Considerations for Healthy Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Sudarshan Dayanidhi
Keyword(s):  
Skeletal Muscle ◽  
Cerebral Palsy ◽  
Endurance Exercise ◽  
Gene Networks ◽  
Healthy Aging ◽  
Mitochondrial Protein ◽  
Mitochondrial Activity ◽  
Endurance Capacity ◽  
Inner Mitochondrial Membrane ◽  
Children With Cerebral Palsy

Skeletal muscle contractile proteins require a constant supply of energy to produce force needed for movement. Energy (ATP) is primarily produced by mitochondrial organelles, located within and around muscle fibers, by oxidative phosphorylation that couples electron flux through the electron transport chain to create a proton gradient across the inner mitochondrial membrane that is in turn used by the ATP synthase. Mitochondrial networks increase in size by biogenesis to increase mitochondrial abundance and activity in response to endurance exercise, while their function and content reduce with constant inactivity, such as during muscle atrophy. During healthy aging, there is an overall decline in mitochondrial activity and abundance, increase in mitochondrial DNA mutations, potential increase in oxidative stress, and reduction in overall muscular capacity. Many of these alterations can be attenuated by consistent endurance exercise. Children with cerebral palsy (CP) have significantly increased energetics of movement, reduced endurance capacity, and increased perceived effort. Recent work in leg muscles in ambulatory children with CP show a marked reduction in mitochondrial function. Arm muscles show that mitochondrial protein content and mitochondria DNA copy number are lower, suggesting a reduction in mitochondrial abundance, along with a reduction in markers for mitochondrial biogenesis. Gene expression networks are reduced for glycolytic and mitochondrial pathways and share similarities with gene networks with aging and chronic inactivity. Given the importance of mitochondria for energy production and changes with aging, future work needs to assess changes in mitochondria across the lifespan in people with CP and the effect of exercise on promoting metabolic health.

Skeletal muscle maximal mitochondrial activity in ambulatory children with cerebral palsy

2021 ◽  
Author(s):  
Sudarshan Dayanidhi ◽  
Elisa H Buckner ◽  
Robin S Redmond ◽  
Henry G Chambers ◽  
Simon Schenk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cerebral Palsy ◽  
Mitochondrial Activity ◽  
Children With Cerebral Palsy

scholarly journals Skeletal muscle mitochondrial protein synthesis and respiration in response to the energetic stress of an ultra-endurance race

2017 ◽  
Vol 123 (6) ◽  
pp. 1516-1524 ◽  
Author(s):  
Adam R. Konopka ◽  
William M. Castor ◽  
Christopher A. Wolff ◽  
Robert V. Musci ◽  
Justin J. Reid ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Endurance Exercise ◽  
Mitochondrial Respiration ◽  
Endurance Athlete ◽  
Control Period ◽  
Mitochondrial Protein ◽  
Mitochondrial Bioenergetics ◽  
Mitochondrial Protein Synthesis ◽  
Ultra Endurance

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s−1·mg tissue−1) and ETS (231 pmol·s−1·mg tissue−1) capacities that rank among the highest published to date in humans. Mitochondrial (3.2-fold), cytoplasmic (2.3-fold), and myofibrillar (1.5-fold) protein synthesis rates were greater during CTR compared with CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (−12 and −14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (−26 and −31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics. NEW & NOTEWORTHY The mechanisms that maintain skeletal muscle function during extreme stresses remain incompletely understood. In the current study, greater rates of mitochondrial protein synthesis during the energetic demands of ultra-endurance exercise may contribute to rapid adaptations in mitochondrial bioenergetics. The endurance athlete herein achieved mitochondrial respiratory capacities among the highest published for humans. Greater mitochondrial protein synthesis during ultra-endurance exercise may contribute to improved mitochondrial respiration and serve as a mechanism to resist cellular energetic stresses.

scholarly journals The Appendicular Lean Mass Index Is a Suitable Surrogate for Muscle Mass in Children with Cerebral Palsy

2019 ◽  
Vol 149 (10) ◽  
pp. 1863-1868
Author(s):  
Ibrahim Duran ◽  
Kyriakos Martakis ◽  
Mirko Rehberg ◽  
Christina Stark ◽  
Anne Koy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cerebral Palsy ◽  
Muscle Mass ◽  
Lean Mass ◽  
Skeletal Muscle Mass ◽  
Rehabilitation Program ◽  
Appendicular Lean Mass ◽  
Significant Difference ◽  
Children With Cerebral Palsy ◽  
Level I

ABSTRACT Background Densitometrically measured lean body mass (LBM) is often used to quantify skeletal muscle mass in children with cerebral palsy (CP). Since LBM depends on the individual's height, the evaluation of $\frac{{{\rm{LBM}}}}{{heigh{t^2}}}\ $ (lean BMI) is often recommended. However, LBM includes not only skeletal muscle mass but also the mass of skin, internal organs, tendons, and other components. This limitation applies to a far lesser extent to the appendicular lean mass index (LMIapp). Objectives The aim of the study was to evaluate skeletal muscle mass in children with CP using total lean BMI (LMItot) and LMIapp. Methods The present study was a monocentric retrospective analysis of prospectively collected data among children and adolescents with CP participating in a rehabilitation program. In total, 329 children with CP [148 females; Gross Motor Function Classification Scale (GMFCS) I, 32 children; GMFCS II, 73 children; GMFCS III, 133 children; GMFCS IV, 78 children; and GMFCS V, 13 children] were eligible for analysis. The mean age was 12.3 ± 2.75 y. Pediatric reference centiles for age-adjusted LMIapp were generated using data from NHANES 1999–2004. Low skeletal muscle mass was defined as a z score for DXA determined LMItot and LMIapp less than or equal to −2.0. Results The z scores for LMIapp were significantly lower than LMItot in children with CP, GMFCS levels II–V (P < 0.001), with the exception of GMFCS level I (P = 0.121), where no significant difference was found. The prevalence of low LMItot (16.1%; 95% CI: 16.1, 20.1%) was significantly lower (P < 0.001) than the prevalence of LMIapp (42.2%; 95% CI: 36.9, 47.9%) in the study population. Conclusions The prevalence of low skeletal muscle mass in children with CP might be underestimated by LMItot. LMIapp is more suitable for the evaluation of skeletal muscle mass in children with CP.

scholarly journals Utilization of lipids during exercise in human subjects: metabolic and dietary constraints

1998 ◽  
Vol 79 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Fred Brouns ◽  
Ger J. van der Vusse
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Dietary Factors ◽  
High Rate ◽  
Strenuous Exercise ◽  
Caffeine Intake ◽  
Limiting Factor ◽  
Endurance Capacity ◽  
Glycogen Depletion ◽  
Dietary Interventions

During endurance exercise, skeletal muscle relies mainly on both carbohydrate (CHO) and fat oxidation to cover energy needs. Numerous scientific studies have shown that increasing the exercise intensity leads to a progressive utilization of CHO. The latter will induce a state of glycogen depletion which is generally recognized as being a limiting factor for the continuation of strenuous exercise. Different dietary interventions have been proposed to overcome this limitation. A high-CHO diet during periods of intense training and competition, as well as CHO intake during exercise, are known to maintain a high rate of CHO oxidation and to delay fatigue. However, it has been recognized also that enhancing fatty acid (FA) oxidation during exercise induces a reduced rate of glycogen degradation, resulting in an improved endurance capacity. This is most strikingly observed as a result of frequent endurance exercise which improves a number of factors known to govern the FA flux and the oxidative capacity of skeletal muscle. Such factors are: (1) blood flow and capillarization; (2) lipolysis of triacylglycerol (TAG) in adipose tissue and circulating TAG and transport of FA from blood plasma to the sarcoplasm; (3) availability and rate of hydrolysis of intramuscular TAG; (4) activation of the FA and transport across the mitochondrial membrane; (5) the activity of enzymes in the oxidative pathway; (6) hormonal adaptations, i.e. sensitivity to catecholamines and insulin. The observation that the plasma FA concentration is an important factor in determining the rate of FA oxidation, and that some dietary factors may influence the rate of FA supply to muscle as well as to the mitochondria, has led to a number of dietary interventions with the ultimate goal to enhance FA oxidation and endurance performance. It appears that experimental data are not equivocal that dietary interventions, such as a high-fat diet, medium-chain TAG-fat emulsions and caffeine intake during exercise, as well as L-carnitine supplementation, do significantly enhance FA oxidation during exercise. So far, only regular endurance exercise can be classified as successful in achieving adaptations which enhance FA mobilization and oxidation.

scholarly journals Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Ronny Lesmana ◽  
Rohit A. Sinha ◽  
Brijesh K. Singh ◽  
Jin Zhou ◽  
Kenji Ohba ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Protein Kinase ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Protein ◽  
Adenosine Monophosphate ◽  
Mitochondrial Activity ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Stimulation Of

Abstract Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time-dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5′adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)- Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3 (LC3), Sequestosome 1 (p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5′adenosine monophosphate-activated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH-mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation.

scholarly journals Skeletal Muscle Mitochondrial Capacity Is Similar In Ambulatory And Non-ambulatory Children With Cerebral Palsy

2020 ◽  
Vol 52 (7S) ◽  
pp. 295-296
Author(s):  
Sudarshan Dayanidhi ◽  
Alexia Rudofski ◽  
Marysol Encarnacíon ◽  
Jill Larson ◽  
Vineeta Swaroop
Keyword(s):  
Skeletal Muscle ◽  
Cerebral Palsy ◽  
Children With Cerebral Palsy ◽  
Mitochondrial Capacity
Sign in / Sign up

Export Citation Format

Share Document