Age-related impeded regeneration of mouse minced anterior tibial muscle
Abstract:
The effect of increasing age on the completeness of anterior tibial muscle regeneration from autotransplants of minced muscle has been studied in Swiss Webster and C57/B6J mice aged 18 to 120 days. A progressively declining capability to regenerate new myofibers was associated with a decreasing phagocytic clearance of implanted myofiber debris. Concurrently, there was decreased presumptive myoblast proliferation and new myofiber formation. The importance of age-related host factors, including nonspecific macrophage activity, in muscle mince regeneration was demonstrated by: (1) the successful regeneration of muscle in heterotransplanted muscle minces from older mice implanted in younger animals and (2) the failure of muscle regeneration when the reverse experiment was performed in syngeneic animals. Heterologous striated muscle from the diaphragm regenerated in the bed of the excised anterior tibial muscle, whereas heterologous cardiac muscle failed to regenerate as expected because of the absence of satellite cells. The failure of phagocytic clearance of implanted myofiber mince and concurrent retardation of regeneration suggests a major age-related nonimmune role of phagocytic macrophages in the early stages of regeneration of anterior tibial muscle from isotopic minced muscle implants.
Insights
Increasing age impairs muscle regeneration by reducing the clearance of debris and the formation of new muscle fibers. Macrophage activity, crucial for this process, declines with age.
Area of Science:
- Muscle regeneration
- Skeletal muscle physiology
- Aging research
Background:
- Autotransplantation of minced muscle is a potential method for skeletal muscle regeneration.
- Age-related changes can significantly impact regenerative capabilities.
- The role of host factors in muscle regeneration is not fully understood.
Purpose of the Study:
- To investigate the effect of increasing age on anterior tibial muscle regeneration from minced muscle autotransplants in mice.
- To determine the relationship between age, phagocytic clearance, myoblast proliferation, and myofiber formation.
- To elucidate the role of age-related host factors, specifically macrophage activity, in muscle regeneration.
Main Methods:
- Studied Swiss Webster and C57/B6J mice aged 18 to 120 days.
- Assessed anterior tibial muscle regeneration following minced muscle autotransplantation.
- Evaluated phagocytic clearance of myofiber debris, presumptive myoblast proliferation, and new myofiber formation.
- Performed heterotransplantation experiments between young and old mice, and syngeneic transplants.
Main Results:
- Increasing age progressively reduced the capability for myofiber regeneration.
- Declining phagocytic clearance of implanted myofiber debris correlated with reduced regeneration.
- Decreased presumptive myoblast proliferation and new myofiber formation were observed in older mice.
- Heterotransplantation of older muscle minces into younger hosts facilitated regeneration, while the reverse failed, highlighting host age importance.
- Heterologous diaphragm muscle regenerated, but cardiac muscle did not, due to satellite cell absence.
Conclusions:
- Age-related decline in phagocytic clearance by macrophages significantly impairs skeletal muscle regeneration.
- Age-related host factors, particularly macrophage activity, play a critical non-immune role in the early stages of muscle regeneration.
- The findings suggest that enhancing macrophage function could be a therapeutic strategy for improving muscle regeneration in older individuals.
