Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.

Journal Article (Journal Article)

Tissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell-derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate the degree of age-associated immunosenescence; moreover, this immunosenescence phenotype was accentuated by fracture injury. The number of CD11b+ Ly6Cintermediate Ly6Ghigh neutrophils significantly decreased with age in association with defective tissue regeneration. In response to fracture injury, the frequencies of neutrophils and associated plasma EVs were significantly higher in fracture calluses than in peripheral blood. Exposure of aged mice to youthful circulation through heterochronic parabiosis increased the number of neutrophils and their correlated Ly6G+ plasma EVs, which were associated with improved fracture healing in aged mice of heterochronic parabiosis pairs. Our findings create a foundation for utilizing specific immune cells and EV subsets as potential biomarkers and therapeutic strategies to promote resilience to stressors during aging.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Baht, GS; Huang, R; Chen, Y-H; Molitoris, KH; Miller, SE; Kraus, VB

Published Date

  • July 2022

Published In

Volume / Issue

  • 21 / 7

Start / End Page

  • e13651 -

PubMed ID

  • 35657721

Pubmed Central ID

  • PMC9282841

Electronic International Standard Serial Number (EISSN)

  • 1474-9726

Digital Object Identifier (DOI)

  • 10.1111/acel.13651


  • eng

Conference Location

  • England