Aging impairs cartilage repair, with young animals exhibiting superior regenerative capacity due to enhanced tissue repairing and reduced inflammation compared to aged counterparts. This study employed single-cell omics to dissect age-dependent immune cell heterogeneity in cartilage injury, revealing a critical deficiency in anti-inflammation macrophage subsets in aged animals. We identified Arg-1 as a central regulator of macrophage polarization, demonstrating that its overexpression rescues impaired repair in aged animals. These findings establish Arg-1 as a novel therapeutic target to counteract age-related declines in cartilage regeneration, offering new insights into macrophage-driven tissue repair mechanisms. The integration of single-cell analysis with functional validation provides a framework for developing precision interventions for age-impaired tissue regeneration.
Chu et al. (Tue,) studied this question.