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.

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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