Catalase, a therapeutic target in the reversal of estrogen-mediated aging

Sharon J. Elliot, Paola Catanuto, Simone Pereira-Simon, Xiaomei Xia, Irena Pastar, Seth Thaller, Cheyanne R. Head, Olivera Stojadinovic, Marjana Tomic-Canic, Marilyn K. Glassberg

Research output: Contribution to journalArticlepeer-review

Abstract

Despite increasing interest in the reversal of age-related processes, there is a paucity of data regarding the effects of post-menopausal-associated estrogen loss on cellular function. We studied human adipose-derived mesenchymal stem cells (hASCs) isolated from women younger than 45 years old (pre-menopause, pre-hASC) or older than 55 years old (post-menopause, post-hASC). In this study, we provide proof of concept that the age-related ineffective functionality of ASCs can be reversed to improve their ability in promoting tissue repair. We found reduced estrogen receptor expression, decreased estrogen receptor activation, and reduced sensitivity to 17β-estradiol in post-hASCs. This correlated with decreased antioxidants (catalase and superoxide dismutase [SOD] expression) and increased oxidative stress compared with pre-hASCs. Increasing catalase expression in post-hASCs restored estrogen receptor (ER) expression and their functional capacity to promote tissue repair as shown in human skin ex vivo wound healing and in vivo mouse model of lung injury. Our results suggest that the consequences of 17β-estradiol decline on the function of hASCs may be reversible by changing the oxidative stress/antioxidant composition.

Original languageEnglish (US)
Pages (from-to)947-962
Number of pages16
JournalMolecular Therapy
Volume30
Issue number2
DOIs
StatePublished - Feb 2 2022

Keywords

  • aging
  • catalase
  • estrogen
  • estrogen receptor
  • mesenchymal stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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