Effect of senolytic drugs in young female mice chemically induced to estropause

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2024-09-21 DOI:10.1016/j.lfs.2024.123073

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引用次数: 0

Abstract

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.

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化学诱导雌性小鼠衰老药物的效果

目的：本研究旨在评估年轻雌性小鼠在诱导雌激素减少并接受衰老药物治疗后的代谢反应和衰老细胞负担：主要方法：在两个月大的小鼠体内注射 4-乙烯基环己烯二环氧化物（VCD）诱导雌激素减少。主要研究结果：VCD诱导的雌激素减少会导致小鼠雌激素减少：与未经处理的周期性小鼠相比，VCD诱导的雌激素导致体重增加和白蛋白浓度降低，但不影响胰岛素敏感性、血脂、肝酶或总蛋白。雌激素减少了脂肪组织中过氧化氢酶的活性，但对脂肪组织和肝组织中的其他氧化还原参数没有显著影响。菲赛汀能降低雌激素过多小鼠肝组织中的 ROS 水平。雌激素停滞不会影响脂肪组织和肝组织中与衰老相关的 beta-半乳糖苷酶活性，但会增加衰老细胞标志物和卵巢纤维化。溶酶治疗并不能降低雌激素停经诱导的卵巢细胞衰老：总体而言，研究结果表明，雌激素减少会导致年轻女性发生轻微的新陈代谢变化，尽管卵巢衰老增加，但解老剂 D + Q 和鱼腥草素没有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.