Impact of ageing on muscle cell regeneration

Carosio, Silvia; Berardinelli, Maria Grazia; Aucello, Michela; Musarò, Antonio

doi:10.1016/j.arr.2009.08.001

Cited by 130 publications

(135 citation statements)

References 110 publications

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“…The final outcome of muscle healing was suggested to be improved only when the microenvironment is modified to be favorable for stem cell functions. [11][12] In the current study, we discovered that muscle healing in the aged muscle was improved by relaxin. The observation of an increased number of stem cells and accelerated muscle regeneration indicates that relaxin administration might have resulted in both stem cell activation and improvement of the local microenvironment in the aged muscle.…”

Section: Discussionmentioning

confidence: 81%

“…[7][8] Also, an improved local microenvironment favorable to satellite cell functioning is especially necessary for the healing of aged muscle. 9,11 Here we hypothesized that relaxin-promoted satellite cell activation and muscle regeneration in younger muscle may be repeatable in the aged muscle. To verify this possibility, GM muscles of 18-month-old mice were laceration-injured and then injected with relaxin on the second day.…”

Section: Relaxin Administration Improves Muscle Healing Of Aged Musclementioning

confidence: 99%

“…5,[7][8][9][10] Recent studies have further indicated that during the healing of aged muscle, the systemic microenvironment is less effective in supporting and maintaining the activation, recruitment, and myogenic fate of resident muscle stem cells but facilitates a conversion to fibrogenic fate. [11][12] Interestingly, evidence has shown that the hostile microenvironment of muscle regeneration is restorable by either neutralizing the activity of transformation growth factor (TGF)-␤1 12 or introducing activated matrix metalloproteinase (MMP)-9 during cell therapy. 13 MMPs have positive roles in muscle healing by promoting muscle regeneration and reducing fibrosis, partially via their ability in inhibiting TGF-␤1.…”

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confidence: 99%

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Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice

Urso

Murray

et al. 2010

The American Journal of Pathology

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The polypeptide hormone relaxin has been proven to be effective in promoting both the remodeling and regeneration of various tissues, including cardiac muscle. In addition, our previous study demonstrated that relaxin is beneficial to skeletal muscle healing by both promoting muscle regeneration and preventing fibrosis formation. However, the molecular and cellular mechanisms of relaxin in regulating both myogenic cell differentiation and muscle healing process are still unclear. In this study, C2C12 mouse myoblasts and primary human myoblasts were treated with relaxin to investigate its potential effect in vitro; relaxin was also injected intramuscularly into the injured site of the mouse on the second day after injury to observe its function in vivo, especially in the aged muscle. Results showed that relaxin promoted myogenic differentiation, migration, and activation of matrix metalloproteinases (MMPs) of cultured myoblasts in vitro. In the injured muscle, relaxin administration promoted the activation of Pax7-positive skeletal muscle satellite cells and increased its local population compared with nontreated control muscles. Meanwhile, both angiogenesis and revascularization were increased, while the extended inflammatory reaction was repressed in the relaxin-treated injured muscle. Moreover, relaxin similarly promoted muscle healing in mice with aged muscle. These results revealed the multiple effects of relaxin in systematically improving muscle healing as well as its potential for clinical applications in patients with skeletal muscle injuries and diseases. (Am J Pathol

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Section: Discussionmentioning

confidence: 81%

Section: Relaxin Administration Improves Muscle Healing Of Aged Musclementioning

confidence: 99%

mentioning

confidence: 99%

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Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice

Urso

Murray

et al. 2010

The American Journal of Pathology

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“…Impaired regenerative properties of muscle, associated with aging, have been shown to be both the result of a decrease in the myogenic progenitor cell number and of a decreased production of secreted chemokines/growth factor, 3,20 including VEGFA. 21 Several studies now suggest that molecules that are involved in embryonic development and more particularly in vasculogenesis and muscle differentiation regulate angiogenesis and ischemic muscle repair in adults.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog-Dependent Regulation of Angiogenesis and Myogenesis Is Impaired in Aged Mice

Renault

Robbesyn

Chapouly

et al. 2013

ATVB

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Objective-The purpose of this study is to further document alteration of signal transduction pathways, more particularly of hedgehog (Hh) signaling, causing impaired ischemic muscle repair in old mice. Approach and Results-We used 12-week-old (young mice) and 20-to 24-month-old C57BL/6 mice (old mice) to investigate the activity of Hh signaling in the setting of hindlimb ischemia-induced angiogenesis and skeletal muscle repair. In this model, delayed ischemic muscle repair observed in old mice was associated with an impaired upregulation of Gli1. Sonic Hh expression was not different in old mice compared with young mice, whereas desert Hh (Dhh) expression was downregulated in the skeletal muscle of old mice both in healthy and ischemic conditions. The rescue of Dhh expression by gene therapy in old mice promoted ischemia-induced angiogenesis and increased nerve density; nevertheless, it failed to promote myogenesis or to increase Gli1 mRNA expression. After further investigation, we found that, in addition to Dhh, smoothened expression was significantly downregulated in old mice. We used smoothened haploinsufficient mice to demonstrate that smoothened knockdown by 50% is sufficient to impair activation of Hh signaling and ischemia-induced muscle repair. Conclusions-The present study demonstrates that Hh signaling is impaired in aged mice

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“…The functional performance of skeletal muscle tissues declines during postnatal life and is compromised in different diseases due to an alteration in muscle fiber composition, atrophy, and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue [162][163][164][165]. Despite no conclusive evidence, it is becoming more widely accepted that the chronic nature of the inflammatory response to tissue damage is a key driver of the fibrotic response in diverse organs and tissues.…”

Section: Muscle Regeneration Is Affected In Aging and Muscle Diseasesmentioning

confidence: 99%

The Basis of Muscle Regeneration

Musarò

2014

Advances in Biology

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Muscle regeneration recapitulates many aspects of embryonic myogenesis and is an important homeostatic process of the adult skeletal muscle, which, after development, retains the capacity to regenerate in response to appropriate stimuli, activating the muscle compartment of stem cells, namely, satellite cells, as well as other precursor cells. Moreover, significant evidence suggests that while stem cells represent an important determinant for tissue regeneration, a "qualified" environment is necessary to guarantee and achieve functional results. It is therefore plausible that the loss of control over these cell fate decisions could lead to a pathological transdifferentiation, leading to pathologic defects in the regenerative process. This review provides an overview about the general aspects of muscle development and discusses the cellular and molecular aspects that characterize the five interrelated and time-dependent phases of muscle regeneration, namely, degeneration, inflammation, regeneration, remodeling, and maturation/functional repair.

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Impact of ageing on muscle cell regeneration

Cited by 130 publications

References 110 publications

Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice

Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice

Hedgehog-Dependent Regulation of Angiogenesis and Myogenesis Is Impaired in Aged Mice

The Basis of Muscle Regeneration

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