TY - JOUR
T1 - Catalase, a therapeutic target in the reversal of estrogen-mediated aging
AU - Elliot, Sharon J.
AU - Catanuto, Paola
AU - Pereira-Simon, Simone
AU - Xia, Xiaomei
AU - Pastar, Irena
AU - Thaller, Seth
AU - Head, Cheyanne R.
AU - Stojadinovic, Olivera
AU - Tomic-Canic, Marjana
AU - Glassberg, Marilyn K.
N1 - Publisher Copyright:
© 2021 The American Society of Gene and Cell Therapy
PY - 2022/2/2
Y1 - 2022/2/2
N2 - 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.
AB - 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.
KW - aging
KW - catalase
KW - estrogen
KW - estrogen receptor
KW - mesenchymal stem cells
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U2 - 10.1016/j.ymthe.2021.06.020
DO - 10.1016/j.ymthe.2021.06.020
M3 - Article
C2 - 34174444
AN - SCOPUS:85114686766
SN - 1525-0016
VL - 30
SP - 947
EP - 962
JO - Molecular Therapy
JF - Molecular Therapy
IS - 2
ER -