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Effect of senolytic drugs in young female mice chemically induced to estropause
Bianca M Ávila1, Bianka M Zanini1, Karina P Luduvico2
1Nutrition College, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Aims:
This study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs.
Main Methods:
Estropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D + Q) or fisetin were given by oral gavage once a month from five to 11 months of age.
Key Findings:
VCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause.
Significance:
Overall, the findings suggest that estropause leads to minor metabolic changes in young females, and the senolytics D + Q and fisetin had no protective effects despite increased ovarian senescence.
Insights
Estropause in young female mice caused minor metabolic changes and increased ovarian senescence. Senolytic drugs, dasatinib plus quercetin (D + Q) and fisetin, did not reduce this cellular senescence.
Area of Science:
- Reproductive biology
- Gerontology
- Metabolic research
Background:
- Estropause, a state of reproductive aging, can impact metabolic health.
- Cellular senescence is implicated in aging and age-related diseases.
- Senolytic drugs target and eliminate senescent cells.
Purpose of the Study:
- To investigate the metabolic effects of induced estropause in young female mice.
- To evaluate the efficacy of senolytic drugs (dasatinib + quercetin and fisetin) in mitigating estropause-induced cellular senescence.
- To assess changes in senescent cell burden and metabolic parameters.
Main Methods:
- Estropause was induced in young female mice using 4-vinylcyclohexene diepoxide (VCD).
- Mice received monthly oral gavage of dasatinib + quercetin (D + Q) or fisetin from five to 11 months of age.
- Metabolic parameters, redox markers, and senescent cell markers in adipose tissue, liver, and ovaries were analyzed.
Main Results:
- VCD-induced estropause increased body mass and decreased albumin but did not affect insulin sensitivity or lipid profiles.
- Estropause reduced catalase activity in adipose tissue and increased ovarian senescence markers and fibrosis.
- Senolytic treatments (D + Q and fisetin) did not reduce estropause-induced ovarian cellular senescence.
Conclusions:
- Estropause in young female mice induces limited metabolic alterations and significant ovarian senescence.
- Current senolytic drugs tested showed no protective effect against estropause-induced ovarian senescence.
- Further research is needed to explore senolytic efficacy in reproductive aging models.
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