Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Yamakawa, Hiroyuki; Kusumoto, Dai; Hashimoto, Hisayuki; Yuasa, Shinsuke

doi:10.3390/ijms21051830

Cited by 102 publications

(79 citation statements)

References 161 publications

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“…Skeletal muscle comprises approximately 40% of the total body weight. Maintenance of skeletal muscle homeostasis is essential for maintaining the body's various functions (Ferreira et al, 2019;Yamakawa et al, 2020). An imbalance in skeletal muscle homeostasis can cause skeletal muscle hyperplasia or atrophy.…”

Section: Introductionmentioning

confidence: 99%

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

et al. 2020

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Although denervated muscle atrophy is common, the underlying molecular mechanism remains unelucidated. We have previously found that oxidative stress and inflammatory response may be early events that trigger denervated muscle atrophy. Isoquercitrin is a biologically active flavonoid with antioxidative and anti-inflammatory properties. The present study investigated the effect of isoquercitrin on denervated soleus muscle atrophy and its possible molecular mechanisms. We found that isoquercitrin was effective in alleviating soleus muscle mass loss following denervation in a dose-dependent manner. Isoquercitrin demonstrated the optimal protective effect at 20 mg/kg/d, which was the dose used in subsequent experiments. To further explore the protective effect of isoquercitrin on denervated soleus muscle atrophy, we analyzed muscle proteolysis via the ubiquitinproteasome pathway, mitophagy, and muscle fiber type conversion. Isoquercitrin significantly inhibited the denervation-induced overexpression of two muscle-specific ubiquitin ligases-muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx), and reduced the degradation of myosin heavy chains (MyHCs) in the target muscle. Following isoquercitrin treatment, mitochondrial vacuolation and autophagy were inhibited, as evidenced by reduced level of autophagy-related proteins (ATG7, BNIP3, LC3B, and PINK1); slow-to-fast fiber type conversion in the target muscle was delayed via triggering expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α); and the production of reactive oxygen species (ROS) in the target muscle was reduced, which might be associated with the upregulation of antioxidant factors (SOD1, SOD2, NRF2, NQO1, and HO1) and the downregulation of ROS production-related factors (Nox2, Nox4, and DUOX1). Furthermore, isoquercitrin treatment reduced the levels of inflammatory factors-interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)-in the target muscle and inactivated the JAK/STAT3 signaling pathway. Overall, isoquercitrin may alleviate soleus muscle atrophy and mitophagy and reverse the slow-to-fast fiber type conversion following denervation via inhibition of oxidative stress and inflammatory response. Our study findings enrich the knowledge regarding the molecular regulatory mechanisms of denervated muscle atrophy and provide a scientific basis for isoquercitrin as a protective drug for the prevention and treatment of denervated muscle atrophy.

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Section: Introductionmentioning

confidence: 99%

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

et al. 2020

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“…Aging is a major risk factor for impaired muscle healing due to tissue fibrosis. Several studies at the cellular and molecular level have examined age‐related differences in muscle healing potential and have identified an age‐related decline in the potency of muscle progenitor cells (MPCs) 44‐46 . It has been reported that exposure to some factors present in the serum of young mice by heterochronic parabiosis (connecting the circulatory systems of a young and an old mouse) can restore the activation of Notch signaling as well as the proliferation and regenerative capacity of aged satellite cells 47 .…”

Section: Introductionmentioning

confidence: 99%

Enhancement of myogenic potential of muscle progenitor cells and muscle healing during pregnancy

et al. 2021

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The decline of muscle regenerative potential with age has been attributed to a diminished responsiveness of muscle progenitor cells (MPCs). Heterochronic parabiosis has been used as a model to study the effects of aging on stem cells and their niches. These studies have demonstrated that, by exposing old mice to a young systemic environment, aged progenitor cells can be rejuvenated. One interesting idea is that pregnancy represents a unique biological model of a naturally shared circulatory system between developing and mature organisms. To test this hypothesis, we evaluated the muscle regeneration potential of pregnant mice using a cardiotoxin (CTX) injury mouse model. Our results indicate that the pregnant mice demonstrate accelerated muscle healing compared to nonpregnant control mice following muscle injury based on improved muscle histology, superior muscle regeneration, and a reduction in inflammation and necrosis. Additionally, we found that MPCs isolated from pregnant mice display a significant improvement of myogenic differentiation capacity in vitro and muscle regeneration in vivo when compared to the MPCs from nonpregnant mice. Furthermore, MPCs from nonpregnant mice display enhanced myogenic capacity when cultured in the presence of serum obtained from pregnant mice. Our proteomics data from these studies provides potential therapeutic targets to enhance the myogenic potential of progenitor cells and muscle repair.

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“…Notably, the capacity to reach this adaptation is almost intact in aged human skeletal muscle [ 55 ]. This is of importance as muscle regenerative capacity is impaired in aged skeletal muscle [ 56 ]. Therefore, aged skeletal muscle cells show a low renewal rate but almost intact mitochondrial function (at least in response to exercise) which somewhat mimics the physiology of cardiomyocytes [ 57 ].…”

Section: The Mitochondria–macrophage Connection Regulates Metabolimentioning

confidence: 99%

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity

Casuso

Huertas

2021

Life

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The incidence and severity of metabolic diseases can be reduced by introducing healthy lifestyle habits including moderate exercise. A common observation in age-related metabolic diseases is an increment in systemic inflammation (the so-called inflammaging) where mitochondrial reactive oxygen species (ROS) production may have a key role. Exercise prevents these metabolic pathologies, at least in part, due to its ability to alter immunometabolism, e.g., reducing systemic inflammation and by improving immune cell metabolism. Here, we review how exercise regulates immunometabolism within contracting muscles. In fact, we discuss how circulating and resident macrophages alter their function due to mitochondrial signaling, and we propose how these effects can be triggered within skeletal muscle in response to exercise. Finally, we also describe how exercise-induced mitochondrial adaptations can help to fight against virus infection. Moreover, the fact that moderate exercise increases circulating immune cells must be taken into account by public health agencies, as it may help prevent virus spread. This is of interest in order to face not only acute respiratory-related coronavirus (SARS-CoV) responsible for the COVID-19 pandemic but also for future virus infection challenges.

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Stem Cell Aging in Skeletal Muscle Regeneration and Disease

Cited by 102 publications

References 161 publications

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

Enhancement of myogenic potential of muscle progenitor cells and muscle healing during pregnancy

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity

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