In vivo GDF3 administration abrogates aging related muscle regeneration delay following acute sterile injury

Andreas Patsalos, Zoltan Simandi, Tristan T. Hays, Matthew Peloquin, Matine Hajian, Isabella Restrepo, Paul M. Coen, Alan J. Russell, L. Nagy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Tissue regeneration is a highly coordinated process with sequential events including immune cell infiltration, clearance of damaged tissues, and immune-supported regrowth of the tissue. Aging has a well-documented negative impact on this process globally; however, whether changes in immune cells per se are contributing to the decline in the body's ability to regenerate tissues with aging is not clearly understood. Here, we set out to characterize the dynamics of macrophage infiltration and their functional contribution to muscle regeneration by comparing young and aged animals upon acute sterile injury. Injured muscle of old mice showed markedly elevated number of macrophages, with a predominance for Ly6Chigh pro-inflammatory macrophages and a lower ratio of the Ly6Clow repair macrophages. Of interest, a recently identified repair macrophage-derived cytokine, growth differentiation factor 3 (GDF3), was markedly downregulated in injured muscle of old relative to young mice. Supplementation of recombinant GDF3 in aged mice ameliorated the inefficient regenerative response. Together, these results uncover a deficiency in the quantity and quality of infiltrating macrophages during aging and suggest that in vivo administration of GDF3 could be an effective therapeutic approach.

Original languageEnglish
JournalAging Cell
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Growth Differentiation Factor 3
Regeneration
Macrophages
Muscles
Wounds and Injuries
Down-Regulation
Cytokines

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Cite this

In vivo GDF3 administration abrogates aging related muscle regeneration delay following acute sterile injury. / Patsalos, Andreas; Simandi, Zoltan; Hays, Tristan T.; Peloquin, Matthew; Hajian, Matine; Restrepo, Isabella; Coen, Paul M.; Russell, Alan J.; Nagy, L.

In: Aging Cell, 01.01.2018.

Research output: Contribution to journalArticle

Patsalos, Andreas ; Simandi, Zoltan ; Hays, Tristan T. ; Peloquin, Matthew ; Hajian, Matine ; Restrepo, Isabella ; Coen, Paul M. ; Russell, Alan J. ; Nagy, L. / In vivo GDF3 administration abrogates aging related muscle regeneration delay following acute sterile injury. In: Aging Cell. 2018.
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AU - Coen, Paul M.

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