Related Experiment Video
Updated: Dec 23, 2025
Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing
Maria Borja-Gonzalez1, Jose C Casas-Martinez1, Brian McDonagh1
1School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, Ireland.
Abstract:
Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H2O2, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.
Insights
In aged mice, elevated inflammation and oxidative stress increase miR-21 in muscle stem cells, impairing regeneration. Inhibiting miR-21 restores muscle-forming potential, suggesting a therapeutic target for age-related muscle decline.
Area of Science:
- Muscle stem cell biology
- Molecular mechanisms of aging
- MicroRNA regulation
Background:
- Aging disrupts skeletal muscle homeostasis, leading to reduced regenerative capacity.
- Molecular pathways driving age-related decline in muscle regeneration are not fully understood.
- MicroRNAs are key regulators of gene expression in tissues, including skeletal muscle.
Purpose of the Study:
- To investigate the role of microRNA-21 (miR-21) in age-related decline of muscle stem cell function.
- To determine how inflammatory cytokines and oxidative stress influence miR-21 expression in muscle cells.
- To assess the therapeutic potential of inhibiting miR-21 for improving muscle regeneration in aged individuals.
Main Methods:
- Studied satellite cells isolated from adult and old mice.
- Assessed the impact of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL6), and hydrogen peroxide (H₂O₂) on miR-21 expression and myoblast function.
- Inhibited miR-21 function in primary myoblasts and evaluated its effect on myogenesis and myotube size.
- Analyzed miR-21's regulatory role in IL6 receptor (IL6R), phosphatase and tensin homolog (PTEN), and forkhead box O3 (FOXO3) signaling pathways.
Main Results:
- Inhibition of miR-21 in satellite cells from old mice enhanced myogenesis.
- Increased levels of TNFα, IL6, and H₂O₂ elevated miR-21 expression in primary myoblasts, reducing their viability and myogenic potential.
- Blocking miR-21 function rescued the diminished myotube size caused by TNFα or IL6 treatment.
- miR-21 was shown to inhibit myogenesis in vitro by regulating IL6R, PTEN, and FOXO3 signaling.
Conclusions:
- Upregulation of miR-21 in aged satellite cells may be triggered by elevated TNFα and IL6.
- Increased miR-21 contributes to skeletal muscle aging and impaired regeneration.
- Targeting miR-21 presents a potential strategy to combat age-related muscle degeneration and enhance regenerative capacity.
Related Concept Videos
01:13Formation of Muscle Fibers from Myoblasts
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
01:37Mitochondria
01:19The Effect of Aging on Tissues
02:23Abnormal Proliferation