Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary

Geroscience. 2022 Jun;44(3):1747-1759. doi: 10.1007/s11357-022-00573-9. Epub 2022 Apr 23.


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.

Keywords: Cell senescence; Dasatinib; Obesity; Ovarian reserve; Quercetin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cellular Senescence
  • Dasatinib / pharmacology
  • Female
  • Mice
  • Mice, Obese
  • Obesity / drug therapy
  • Ovary*
  • Quercetin / pharmacology
  • Senotherapeutics*


  • Senotherapeutics
  • Quercetin
  • Dasatinib