Aging Delays Epimorphic Regeneration in Mice

Regina Brunauer*, Ian G. Xia, Shabistan N. Asrar, Lindsay A. Dawson, Connor P. Dolan, Ken Muneoka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Epimorphic regeneration is a multitissue regeneration process where amputation does not lead to scarring, but blastema formation and patterned morphogenesis for which cell plasticity and concerted cell-cell interactions are pivotal. Tissue regeneration declines with aging, yet if and how aging impairs epimorphic regeneration is unknown. Here, we show for the first time that aging derails the spatiotemporal regulation of epimorphic regeneration in mammals, first, by exacerbating tissue histolysis and delaying wound closure, and second, by impairing blastema differentiation and skeletal regrowth. Surprisingly, aging did not limit stem cell availability in the blastema but reduced osteoblast-dependent bone formation. Our data suggest that aging delays regeneration not by stem cell exhaustion, but functional defects of differentiated cells that may be driven by an aged wound environment and alterations in the spatiotemporal regulation of regeneration events. Our findings emphasize the importance of accurate timing of signaling events for regeneration and highlight the need for carefully timed interventions in regenerative medicine.

Original languageEnglish
Pages (from-to)1726-1733
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number10
StatePublished - 1 Oct 2021
Externally publishedYes


  • Cell differentiation
  • Osteoblasts
  • Regenerative medicine
  • Stem cells
  • Wound healing


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