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Updated: Feb 11, 2026

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery
Published on: May 11, 2011
Myeloid Cell Responses to Contraction-induced Injury Differ in Muscles of Young and Old Mice
Darcée D Sloboda1, Lemuel A Brown2, Susan V Brooks1,2
1Department of Biomedical Engineering, University of Michigan, Ann Arbor.
Abstract:
Myeloid cells play a critical role in regulating muscle degeneration and regeneration. Thus, alterations with aging in the myeloid cell response to muscle damage may affect the progression of the injury in old animals. We hypothesized that neutrophil levels remain elevated and that macrophage accumulation is reduced or delayed in injured muscles of old compared with young animals. Muscles of young and old mice were injured with lengthening contractions and analyzed 2 or 5 days later. Regardless of age, neutrophil (Gr-1+) and macrophage (CD68+) content increased dramatically by Day 2. Between 2 and 5 days, macrophages increased further, whereas neutrophils declined to a level that in old muscles was not different from uninjured controls. M2 macrophages (CD163+) also increased between 2 and 5 days, reaching higher levels in muscles of old mice than in young mice. Although no evidence of persisting neutrophils or reduced M2 accumulation in old muscle was found, total macrophage accumulation was lower in old mice. Furthermore, messenger RNA levels showed age-related changes in macrophage-associated genes that may indicate alterations in myeloid cell function. Overall, differences between muscles of old and young mice in the inflammatory response through the early stages of injury may contribute to defects in muscle regeneration.
Insights
Aging alters the muscle
Area of Science:
- Muscle regeneration and aging research
- Immunology and cell biology
- Skeletal muscle physiology
Background:
- Myeloid cells are crucial for muscle repair after injury.
- Aging may impair the myeloid cell response, affecting muscle healing.
- Understanding age-related changes in myeloid cells is vital for muscle health.
Purpose of the Study:
- To investigate age-related differences in myeloid cell accumulation and function following muscle injury.
- To test the hypothesis that old mice exhibit elevated neutrophils and reduced/delayed macrophages in injured muscle.
Main Methods:
- Inducing muscle injury via lengthening contractions in young and old mice.
- Analyzing neutrophil (Gr-1+) and macrophage (CD68+, CD163+) content at 2 and 5 days post-injury.
- Measuring messenger RNA (mRNA) levels of macrophage-associated genes.
Main Results:
- Both young and old mice showed increased neutrophils and macrophages by Day 2.
- Neutrophils decreased by Day 5, while total macrophages increased, but were lower in old mice.
- M2 macrophages (CD163+) increased in both groups, with higher levels in old mice by Day 5.
- Age-related changes in macrophage gene expression suggest altered function in older mice.
Conclusions:
- Contrary to hypothesis, neutrophils did not persist, and M2 macrophages accumulated in old muscle.
- Total macrophage accumulation was lower in old mice after injury.
- Altered myeloid cell responses, particularly macrophage dynamics and gene expression, may contribute to impaired muscle regeneration in aging.
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