scholarly journals Mitochondrial Mechanisms of Neuromuscular Junction Degeneration with Aging

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 197 ◽  
Author(s):  
Maria-Eleni Anagnostou ◽  
Russell T. Hepple
Keyword(s):  
Neuromuscular Junction ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Permeability Transition ◽  
Motor Units ◽  
Age Related ◽  
Increased Risk ◽  
Aging Muscle

Skeletal muscle deteriorates with aging, contributing to physical frailty, poor health outcomes, and increased risk of mortality. Denervation is a major driver of changes in aging muscle. This occurs through transient denervation-reinnervation events throughout the aging process that remodel the spatial domain of motor units and alter fiber type. In advanced age, reinnervation wanes, leading to persistent denervation that accelerates muscle atrophy and impaired muscle contractility. Alterations in the muscle fibers and motoneurons are both likely involved in driving denervation through destabilization of the neuromuscular junction. In this respect, mitochondria are implicated in aging and age-related neurodegenerative disorders, and are also likely key to aging muscle changes through their direct effects in muscle fibers and through secondary effects mediated by mitochondrial impairments in motoneurons. Indeed, the large abundance of mitochondria in muscle fibers and motoneurons, that are further concentrated on both sides of the neuromuscular junction, likely renders the neuromuscular junction especially vulnerable to age-related mitochondrial dysfunction. Manifestations of mitochondrial dysfunction with aging include impaired respiratory function, elevated reactive oxygen species production, and increased susceptibility to permeability transition, contributing to reduced ATP generating capacity, oxidative damage, and apoptotic signaling, respectively. Using this framework, in this review we summarize our current knowledge, and relevant gaps, concerning the potential impact of mitochondrial impairment on the aging neuromuscular junction, and the mechanisms involved.

scholarly journals Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

2016 ◽  
Vol 26 (4) ◽  
Author(s):  
Simone Mosole ◽  
Ugo Carraro ◽  
Helmut Kern ◽  
Stefan Loefler ◽  
Sandra Zampieri
Keyword(s):  
Motor Neurons ◽  
Fiber Type ◽  
Functional Decline ◽  
Muscle Fibers ◽  
Motor Units ◽  
The Body ◽  
Age Related ◽  
Immuno Histochemistry ◽  
High Level ◽  
And Function

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977.

What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature

2019 ◽  
Vol 25 (28) ◽  
pp. 3005-3010
Author(s):  
Georges Samouri ◽  
Alexandre Stouffs ◽  
Lionel V. Essen ◽  
Olivier Simonet ◽  
Marc De Kock ◽  
...  
Keyword(s):  
Frail Elderly ◽  
Muscle Fibers ◽  
Motor Units ◽  
The Elderly ◽  
Hepatic Function ◽  
Volume Of Distribution ◽  
Neuromuscular Blocking ◽  
Cancer Surgery ◽  
Old People ◽  
Age Related

Introduction: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. Method: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. Results: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. : Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. : No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. Conclusion: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

scholarly journals Caloric restriction: powerful protection for the aging heart and vasculature

2011 ◽  
Vol 301 (4) ◽  
pp. H1205-H1219 ◽  
Author(s):  
Edward P. Weiss ◽  
Luigi Fontana
Keyword(s):  
Arterial Stiffness ◽  
Cardiovascular System ◽  
Current Knowledge ◽  
Left Ventricular Diastolic Function ◽  
The United States ◽  
Left Ventricular ◽  
Cvd Risk ◽  
Beneficial Effects ◽  
Age Related ◽  
Increased Risk

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.

Progress of Age-Related Changes in Properties of Motor Units in the Gastrocnemius Muscle of Rats

2004 ◽  
Vol 92 (3) ◽  
pp. 1357-1365 ◽  
Author(s):  
Miho Sugiura ◽  
Kenro Kanda
Keyword(s):  
Gastrocnemius Muscle ◽  
Muscle Tension ◽  
Muscle Fibers ◽  
Motor Units ◽  
Medial Gastrocnemius ◽  
Motor Nucleus ◽  
Twitch Contraction ◽  
Age Related ◽  
Old Rats ◽  
Whole Muscle

The mechanical properties of individual motor units in the medial gastrocnemius muscle, as well as the whole muscle properties and innervating motor nucleus, were investigated in dietary-restricted, male Fischer 344/DuCrj rats at ages of 4, 7, 12, 21/22, 27, 31, and 36 mo. The tetanic tension of the type S units continuously increased until the age of 36 mo. Those of type FF and FR units declined from 21/22 to 27 mo of age but did not change further while the whole muscle tension decreased greatly. The atrophy of muscle fibers, the decline in motoneuron number and axonal conduction velocity, and the decrease in the posttetanic potentiation of twitch contraction of motor units seemed to start after 21/22 mo of age and were accelerated with advancing age. Prolongation of twitch contraction time was evident for only type S and FR units in 36-mo-old rats. The fatigue index was greatly increased for type FF units in 36-mo-old rats. These findings indicated that the progress of changes in various properties occurring in the senescent muscle was different in terms of their time course and degree and also dependent on the types of motor unit. The atrophy and decrease in specific tension of muscle fibers affected the decline in tension output of motor units. This was effectively compensated for by the capture of denervated muscle fibers over time.

Valvular heart disease and calcification in CKD: more common than appreciated

2019 ◽  
Vol 35 (12) ◽  
pp. 2046-2053 ◽  
Author(s):  
Pablo Ureña-Torres ◽  
Luis D’Marco ◽  
Paolo Raggi ◽  
Xavier García–Moll ◽  
Vincent Brandenburg ◽  
...  
Keyword(s):  
Heart Disease ◽  
Vascular Calcification ◽  
Heart Valves ◽  
Current Knowledge ◽  
Arterial Disease ◽  
Therapeutic Implications ◽  
Risk Of Death ◽  
Age Related ◽  
Increased Risk ◽  
Clinical Consequences

Abstract Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

Development of homogeneous fast and slow motor units in the neonatal mouse soleus muscle

Development ◽  
1990 ◽  
Vol 109 (3) ◽  
pp. 723-732
Author(s):  
T. Fladby ◽  
J.K. Jansen
Keyword(s):  
Lucifer Yellow ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Age Groups ◽  
Motor Units ◽  
Substantial Part ◽  
Synapse Elimination ◽  
Glycogen Depletion ◽  
Subsequent Period ◽  
Type Composition

We studied the fiber type composition and contractile properties of mouse soleus motor units at 2 days, 5 days and 2 weeks of age. We used Lucifer Yellow injection to mark muscle fibers belonging to the same motor unit in the two youngest age groups, and the traditional method of glycogen depletion in the oldest. The age groups were chosen because 2 days is at the end of muscle fiber production; 5 days is at the start of synapse elimination in the muscle and 2 weeks is at the end. Muscle fibers were classified as fast (F) or slow (S) on the basis of their myosin heavy chain (MHC) content, as determined by different monoclonal antibodies. Motor units are already dominated by either F- or S-fibers at 2 days, suggesting an early preferential innervation of the two types of fibers. A substantial part of the remaining refinement of the innervation takes place during the next 3 days, while the total number of terminals in the muscle remains constant. This is most easily explained by an exchange of aberrant for correct synapses during this period. A smaller part of the refinement of the innervation occurs during the subsequent period of synapse elimination.

Mitochondrial Permeability Transition Pore Sealing Agents and Antioxidants Protect Oxidative Stress and Mitochondrial Dysfunction Induced by Naproxen, Diclofenac and Celecoxib

Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 598-605 ◽  
Author(s):  
Ahmad Salimi ◽  
Mohammad Reza Neshat ◽  
Parvaneh Naserzadeh ◽  
Jalal Pourahmad
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Isolated Rat Heart ◽  
Atp Depletion ◽  
Mitochondrial Permeability ◽  
Pore Sealing ◽  
Increased Risk

AbstractNonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen, diclofenac and celecoxib used to reduce pain. Many of these drugs have been associated with an increased risk of cardiovascular disease (CVD). The molecular mechanism(s) by which NSAIDs induce CVD up to now is unknown. We investigated the effects of naproxen, diclofenac and celecoxib with different structures and mechanism action on isolated rat heart mitochondria. All tested NSAIDs increased reactive oxygen species (ROS) formation, mitochondrial membrane collapse (MMP), mitochondrial swelling, lipid peroxidation, and glutathione and ATP depletion, which all of them play important roles in developing cardiotoxicity. We reported that mitochondrial permeability transition (MPT) pore sealing agents and antioxidants have the capacity to significantly prevent mitochondrial toxicity. Therefore, the inhibition of mitochondrial oxidative stress and mitochondrial dysfunction by MPT pore sealing agents and antioxidants can double confirm NSAID-induced cardiomyocytes toxicity is resulted from induction of apoptosis signaling trough ROS-mediated mitochondrial permeability transition.

scholarly journals Eicosapentaenoic acid changes muscle transcriptome and intervenes in aging-related fiber type transition in male mice

2020 ◽  
Author(s):  
Hiroki Yamazaki ◽  
Mayu Nishimura ◽  
Masaaki Uehara ◽  
Akiko Kuribara-Souta ◽  
Motohisa Yamamoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Eicosapentaenoic Acid ◽  
Grip Strength ◽  
Muscle Mass ◽  
Fiber Type ◽  
Male Mice ◽  
Type Transition ◽  
Age Related ◽  
Normal Chow ◽  
Aging Muscle

Age-related sarcopenia is associated with a variety of changes in skeletal muscle. These changes are interrelated with each other and associated with systemic metabolism, the details of which, however, are largely unknown. Eicosapentaenoic acid (EPA) is a promising nutrient against sarcopenia and has multifaceted effects on systemic metabolism. In this study, we hypothesized that the aging process in skeletal muscle can be intervened by the administration of EPA. Seventy-five-week-old male mice were assigned to groups fed with EPA-deprived diet (EPA-) or EPA-enriched diet with 1wt% EPA (EPA+) for 12 weeks. Twenty-four-week-old male mice fed with normal chow were also analyzed. At baseline, the grip strength of the aging mice was lower than that of the young mice. After 12 weeks, EPA+ showed similar muscle mass but increased grip strength compared to EPA-. EPA+ displayed higher insulin sensitivity than EPA-. Immunohistochemistry and gene expression analysis of myosin heavy chains (MyHCs) revealed fast-to-slow fiber type transition in aging muscle, which was partially inhibited by EPA. RNA-seq analysis suggested that EPA supplementation exerts pathway-specific effects in skeletal muscle including the signatures of slow-to-fast fiber type transition. In conclusion, we revealed that aging skeletal muscle in male mice­ shows lower grip strength and fiber type changes, both of which can be inhibited by EPA supplementation irrespective of muscle mass alteration.

Fiber architecture and histochemistry in the cat neck muscle, biventer cervicis

1988 ◽  
Vol 60 (1) ◽  
pp. 46-59 ◽  
Author(s):  
F. J. Richmond ◽  
J. B. Armstrong
Keyword(s):  
Fiber Type ◽  
Muscle Fibers ◽  
Motor Units ◽  
Neck Muscle ◽  
Fiber Architecture ◽  
Cross Sectional ◽  
Lateral Muscle ◽  
Tension Properties ◽  
In Series ◽  
Length Changes

1. Biventer cervicis (BC) is an anatomically complex muscle that is divided by tendinous inscriptions into five in-series compartments of motor units. We have analyzed the fiber architecture and fiber-type composition of these different compartments using microdissection and histochemical methods. 2. BC narrows as it runs rostrally, but its in-series compartments have similar cross-sectional areas. The tapered shape of BC comes about because tendinous inscriptions and the tendon of insertion are oriented obliquely and muscle fibers attach in a progressively offset fashion from the medial to the lateral muscle edge. 3. Individual compartments of BC differ from one another in their architecture. The rostral two compartments (1 and 2) contain fibers of similar length that run between two plates of tendinous tissue. Compartments 3 and 4 are divided into two or three in-parallel subvolumes whose fiber bundles differ in their lengths and sites of attachment. Compartment 5 is the most variable in its structure. In some cats it is separated from compartment 4 by a tendinous inscription, but in other cats, it blends with a dorsomedial part of compartment 4 to form a single subvolume. 4. The relative lengths of fibers in different compartments were analyzed when the head and neck were held in different postures. Fibers in rostromedial regions were stretched more effectively when the head was flexed at suboccipital joints, and appeared to be less sensitive to movements at lower cervical joints. Movements across lower cervical joints produced substantial length changes in caudolateral parts of BC. 5. Muscle fibers of different histochemical types were not distributed evenly within each muscle compartment. Slow, oxidative (SO) fibers accounted for the majority of fibers near the nuchal midline but for only 30%-45% of fibers in lateral muscle regions. Proportions of fast, glycolytic (FG) fibers were greatest in lateral regions. Fast, oxidative-glycolytic (FOG) fibers were distributed quite uniformly throughout each compartment. 6. The specialized architecture of BC may shape its physiological capabilities. The complex internal structures of different compartments may alter the length-tension properties of BC.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

2013 ◽  
Vol 305 (4) ◽  
pp. H459-H476 ◽  
Author(s):  
Emanuele Marzetti ◽  
Anna Csiszar ◽  
Debapriya Dutta ◽  
Gauthami Balagopal ◽  
Riccardo Calvani ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cardiovascular System ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Late Life ◽  
Age Related ◽  
Functional Consequences ◽  
Cardiovascular Aging ◽  
The Life Course

Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The age-related accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD.

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