Publication Type

Journal Article

Version

publishedVersion

Publication Date

9-2018

Abstract

Physicians have observed that surgical wounds in the elderly heal with thinner scars than wounds in young patients. Understanding this phenomenon may reveal strategies for promoting scarless wound repair. We show that full-thickness skin wounds in aged but not young mice fully regenerate. Exposure of aged animals to blood from young mice by parabiosis counteracts this regenerative capacity. The secreted factor, stromal-derived factor 1 (SDF1), is expressed at higher levels in wounded skin of young mice. Genetic deletion of SDF1 in young skin enhanced tissue regeneration. In aged mice, enhancer of zeste homolog 2 (EZH2) and histone H3 lysine 27 trimethylation are recruited to the SDF1 promoter at higher levels, and pharmacologic inhibition of EZH2 restores SDF1 induction and prevents tissue regeneration. Similar age-dependent EZH2-mediated SDF1 suppression occurs in human skin. Our findings counter the current dogma that tissue function invariably declines with age and suggest new therapeutic strategies in regenerative medicine.

Keywords

tissue regeneration, scar, aging, skin, epigenetics, SDF1, CXCL12, organ regeneration

Discipline

Econometrics | Medical Sciences

Research Areas

Econometrics

Publication

Cell Reports

Volume

24

Issue

13

First Page

3383

Last Page

3392

ISSN

2211-1247

Identifier

10.1016/j.celrep.2018.12.056

Publisher

Elsevier (Cell Press): OAJ / Elsevier

Copyright Owner and License

Authors

Additional URL

https://doi.org/10.1016/j.celrep.2018.12.056

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