Myostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies

Baig, Mohammad Hassan; Ahmad, Khurshid; Moon, Jun Sung; Park, Soyoung; Lim, Jeong Ho; Chun, Hee Jin; Qadri, Afsha Fatima; Hwang, Ye Chan; Jan, Arif Tasleem; Ahmad, Syed Sayeed; Ali, Shahid; Shaikh, Sibhghatulla; Lee, Eun Ju; Choi, Inho

doi:10.3389/fphys.2022.876078

Cited by 38 publications

(27 citation statements)

References 182 publications

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“…Myostatin, as a muscle atrophy index, increases in the older population [ 7 ]. It binds to the activin type II receptor and suppresses muscle growth signaling pathways, protein synthesis, satellite cell activation, and negatively regulates myogenic differentiation and myofiber hypertrophy [ 8 , 9 ]. In contrast, follistatin as a member of the transforming growth factor-β family, blocking myostatin [ 4 ] and activating satellite cells [ 10 ], leading to hypertrophy and preventing age-associated muscle wastes.…”

Section: Introductionmentioning

confidence: 99%

Effects of functional training with blood occlusion on the irisin, follistatin, and myostatin myokines in elderly men

Pazokian

Amani-Shalamzari

Rajabi

2022

Eur Rev Aging Phys Act

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Background This study aimed to determine the efficacy of functional training with and without blood flow restriction (BFR) on muscle hypertrophy indices and strength in older men. Methods Thirty older adults (67.7 ± 5.8 years) were randomly assigned to three groups: functional training (FT), functional training with BFR (FTBFR), and control (C). Participants in experimental groups were trained in three sessions per week for six weeks. They performed 11 whole body exercises, in 2–4 sets of 10 repetitions. FTBFR group wore pneumatic cuffs on their extremities that began with 50% of estimated arterial occlusion pressure which increased by 10% every two weeks. Blood samples were obtained, and static strength tests were evaluated at baseline and after the training program. A One-Way Analysis of Covariance was used to interpret the data. Results A significant increase in follistatin levels (p = 0.002) and reduction in myostatin levels (p = 0.001) were observed in FT and FTBFR groups; there was a considerable increase in the F:M ratio in both training groups (p = 0.001), whereas it decreased in C group. These changes were accompanied by significant improvements in handgrip (p = 0.001) and shoulder girdle (p = 0.001) strength in both experimental groups, especially in the FTBFR group. However, the levels of irisin were not statistically changed following interventions (p = 0.561). Conclusion The findings showed that FT was effective in increasing circulating biomarkers involved in hypertrophy in older adults while adding BFR to FT had a slight increase in these biomarkers but had a tremendous increase in muscle strength.

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Section: Introductionmentioning

confidence: 99%

Effects of functional training with blood occlusion on the irisin, follistatin, and myostatin myokines in elderly men

Pazokian

Amani-Shalamzari

Rajabi

2022

Eur Rev Aging Phys Act

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“…This result indicates that MID-35 peptide was delivered to skeletal muscle as the intact form by ItP and the delivered MID-35 functioned in skeletal muscle. In previous reports, the weight of the tibialis anterior muscle was found to increase by a similar amount (1.33-fold) upon intramuscular injection of MID-35 [ 20 ], though it should be noted that the dose of MID-35 for ItP (75 nmol) was higher than that for intramuscular injection (30 nmol). Thus, we succeeded in increasing skeletal muscle weight by delivering MID-35 with the non-invasive intramuscular delivery technology ItP in this study.…”

Section: Discussionmentioning

confidence: 73%

“…Myostatin (growth differentiation factor-8, GDF-8) is a member of the transforming growth factor-β (TGF-β) superfamily and negatively regulates muscle growth by binding to activin type I and type II receptors and thus activating Smad 2/3 signaling [ 4 , 5 , 6 , 7 , 8 ]. Accordingly, myostatin inhibitors, including antibody, recombinant protein, and peptide, have been shown to be useful tools for inducing muscle growth, leading to the promising treatment of muscle atrophic disorders, such as muscular dystrophy, sarcopenia, and cancer-associated cachexia [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. However, clinical use for improving muscle wasting have not been achieved yet; hence, there is still room for the new strategies.…”

Section: Introductionmentioning

confidence: 99%

Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis

et al. 2023

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Sarcopenia is a major public health issue that affects older adults. Myostatin inhibitory-D-peptide-35 (MID-35) can increase skeletal muscle and is a candidate therapeutic agent, but a non-invasive and accessible technology for the intramuscular delivery of MID-35 is required. Recently, we succeeded in the intradermal delivery of various macromolecules, such as siRNA and antibodies, by iontophoresis (ItP), a non-invasive transdermal drug delivery technology that uses weak electricity. Thus, we expected that ItP could deliver MID-35 non-invasively from the skin surface to skeletal muscle. In the present study, ItP was performed with a fluorescently labeled peptide on mouse hind leg skin. Fluorescent signal was observed in both skin and skeletal muscle. This result suggested that the peptide was effectively delivered to skeletal muscle from skin surface by ItP. Then, the effect of MID-35/ItP on skeletal muscle mass was evaluated. The skeletal muscle mass increased 1.25 times with ItP of MID-35. In addition, the percentage of new and mature muscle fibers tended to increase, and ItP delivery of MID-35 showed a tendency to induce alterations in the levels of mRNA of genes downstream of myostatin. In conclusion, ItP of myostatin inhibitory peptide is a potentially useful strategy for treating sarcopenia.

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“…15,30,37 Several animal studies have shown that myostatin inhibition was associated with increased muscle mass and tumor regression. 15,30,37 Further studies are required to better understand the role and mechanism of muscle metabolism in cancer care.…”

Section: Discussionmentioning

confidence: 99%

Sarcopenia predicts short‐term treatment‐related toxicity in patients undergoing curative‐intent therapy for head and neck cancer: A systematic review and meta‐analysis

Mascarella,

Ferdus,

Vendra

et al. 2024

Head & Neck

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Sarcopenia is an increasingly recognized biomarker associated with poorer outcomes. The objective of this study was to ascertain the effect of sarcopenia on treatment tolerance and short‐term toxicity in head and neck cancer (HNC). A systematic review was performed using multiple databases. An inverse‐variation, random‐effects model was used to perform the meta‐analysis to evaluate the effect of sarcopenia on severe treatment toxicity and poor treatment tolerance. Sixteen observational studies, including 3187 patients with HNC, were analyzed. The combined odds ratio (OR) for severe treatment toxicity and tolerance was 2.22 (95%CI 1.50–3.29) and 1.40 (95%CI 0.84–2.32), respectively. The effect of sarcopenia on short‐term severe treatment toxicity was similar with upfront surgery (OR 2.03, 95%CI 1.22–3.37) and definitive radiotherapy (OR 2.24, 95%CI 1.18–4.27) Patients with sarcopenia are more than twice as likely to suffer a short‐term treatment‐related toxicity when undergoing curative‐intent HNC treatment.

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Myostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies

Cited by 38 publications

References 182 publications

Effects of functional training with blood occlusion on the irisin, follistatin, and myostatin myokines in elderly men

Effects of functional training with blood occlusion on the irisin, follistatin, and myostatin myokines in elderly men

Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis

Sarcopenia predicts short‐term treatment‐related toxicity in patients undergoing curative‐intent therapy for head and neck cancer: A systematic review and meta‐analysis

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