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Updated: Sep 26, 2025
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary
Jéssica D Hense1, Driele N Garcia2, José V Isola3,4
1Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, RS, Pelotas, Brazil.
Abstract:
Senescent cells are in a cell cycle arrest state and accumulate with aging and obesity, contributing to a chronic inflammatory state. Treatment with senolytic drugs dasatinib and quercetin (D + Q) can reduce senescent cell burden in several tissues, increasing lifespan. Despite this, there are few reports about senescent cells accumulating in female reproductive tissues. Therefore, the aim of the study was to characterize the ovarian reserve and its relationship with cellular senescence in genetically obese mice (ob/ob). In experiment 1, ob/ob (n = 5) and wild-type (WT) mice (n = 5) at 12 months of age were evaluated. In experiment 2, 2-month-old female ob/ob mice were treated with senolytics (D + Q, n = 6) or placebo (n = 6) during the 4 months. Obese mice had more senescent cells in ovaries, indicated by increased p21 and p16 and lipofuscin staining and macrophage infiltration. Treatment with D + Q significantly reduced senescent cell burden in ovaries of obese mice. Neither obesity nor treatment with D + Q affected the number of ovarian follicles. In conclusion, our data indicate that obesity due to leptin deficiency increases the load of senescent cells in the ovary, which is reduced by treatment by senolytics. However, neither obesity nor D + Q treatment affected the ovarian reserve.
Insights
Obesity increases senescent cells in ovaries, but senolytic drugs dasatinib and quercetin reduce this burden. Neither obesity nor treatment impacted ovarian reserve in mice.
Area of Science:
- Reproductive biology
- Cellular senescence
- Obesity research
Background:
- Cellular senescence, a state of cell cycle arrest, accumulates with aging and obesity, promoting chronic inflammation.
- Senolytic drugs, such as dasatinib and quercetin (D+Q), can reduce senescent cell burden and extend lifespan.
- Limited research exists on senescent cell accumulation in female reproductive tissues.
Purpose of the Study:
- To investigate the presence and impact of cellular senescence in the ovaries of genetically obese mice (ob/ob).
- To determine if senolytic treatment (D+Q) can reduce ovarian senescent cell burden in obese mice.
- To assess the effect of obesity and senolytic treatment on ovarian reserve.
Main Methods:
- Comparison of ovarian senescence markers (p21, p16, lipofuscin, macrophage infiltration) between 12-month-old obese (ob/ob) and wild-type (WT) mice.
- Treatment of 2-month-old obese mice with D+Q or placebo for 4 months.
- Evaluation of ovarian senescence and ovarian follicle counts post-treatment.
Main Results:
- Obese mice exhibited increased senescent cells in their ovaries compared to WT mice.
- Senolytic treatment with D+Q significantly reduced senescent cell burden in the ovaries of obese mice.
- Neither obesity nor D+Q treatment affected the number of ovarian follicles, indicating no impact on ovarian reserve.
Conclusions:
- Leptin deficiency-induced obesity increases ovarian senescent cell load.
- Senolytic therapy effectively reduces senescent cells in the ovaries of obese mice.
- Obesity and senolytic treatment did not alter the ovarian reserve in this mouse model.
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