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Catalase, a therapeutic target in the reversal of estrogen-mediated aging.
Elliot SJ, Catanuto P, Pereira-Simon S, Xia X, Pastar I, Thaller S, Head CR,
Stojadinovic O, Tomic-Canic M, Glassberg MK
Submitted Externally on 3/9/2022
Molecular therapy : the journal of the American Society of Gene Therapy
Volume : Pages
30 : 947 - 962
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 17ß-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 17ß-estradiol decline on the function of hASCs
may be reversible by changing the oxidative stress/antioxidant composition.
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Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
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