Related Experiment Video
Updated: Aug 1, 2025
Minimally Invasive Muscle Embedding MIME - A Novel Experimental Technique to Facilitate Donor-Cell-Mediated Myogenesis
Published on: August 24, 2017
Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration
Neuza S Sousa1, Margarida F Brás1, Inês B Antunes1
1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Abstract:
Age-related decline in skeletal muscle regenerative capacity is multifactorial, yet the contribution of immune dysfunction to regenerative failure is unknown. Macrophages are essential for effective debris clearance and muscle stem cell activity during muscle regeneration, but the regulatory mechanisms governing macrophage function during muscle repair are largely unexplored. Here, we uncover a new mechanism of immune modulation operating during skeletal muscle regeneration that is disrupted in aged animals and relies on the regulation of macrophage function. The immune modulator mesencephalic astrocyte-derived neurotrophic factor (MANF) is induced following muscle injury in young mice but not in aged animals, and its expression is essential for regenerative success. Regenerative impairments in aged muscle are associated with defects in the repair-associated myeloid response similar to those found in MANF-deficient models and could be improved through MANF delivery. We propose that restoring MANF levels is a viable strategy to improve myeloid response and regenerative capacity in aged muscle.
Insights
Aging impairs muscle regeneration by disrupting macrophage function. Restoring mesencephalic astrocyte-derived neurotrophic factor (MANF) levels can improve the immune response and enhance muscle repair in older individuals.
Area of Science:
- Immunology
- Muscle Biology
- Aging Research
Background:
- Skeletal muscle regeneration declines with age, but immune dysfunction's role is unclear.
- Macrophages are crucial for muscle repair, yet regulatory mechanisms remain poorly understood.
Purpose of the Study:
- Investigate immune modulation in age-related muscle regeneration failure.
- Identify mechanisms regulating macrophage function during muscle repair.
Main Methods:
- Compared muscle regeneration in young and aged mice post-injury.
- Assessed the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in macrophage function and repair.
- Evaluated MANF delivery as a therapeutic strategy.
Main Results:
- MANF is induced in young mice after injury but not in aged mice, correlating with regenerative success.
- Aged muscle regeneration defects resemble MANF-deficient models, showing impaired myeloid response.
- MANF delivery improved myeloid response and regeneration in aged muscle models.
Conclusions:
- MANF is a key immune modulator in muscle regeneration, disrupted in aging.
- Restoring MANF levels offers a potential strategy to enhance myeloid function and muscle regeneration in aged individuals.
Related Concept Videos
01:21Satellite Stem Cells and Muscular Dystrophy
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
01:40Cell-mediated Immune Responses
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...