Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, RS, Pelotas, Brazil.
Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
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.
衰老细胞处于细胞周期停滞状态，并随着衰老和肥胖而积累，导致慢性炎症状态。使用衰老细胞溶解药物达沙替尼和槲皮素（D+Q）治疗可以减少几种组织中的衰老细胞负担，从而延长寿命。尽管如此，关于衰老细胞在女性生殖组织中积累的报道很少。因此，本研究的目的是描述肥胖基因（ob/ob）小鼠的卵巢储备及其与细胞衰老的关系。在实验 1 中，12 个月大的 ob/ob（n=5）和野生型（WT）小鼠（n=5）进行了评估。在实验 2 中，2 个月大的雌性 ob/ob 小鼠在 4 个月内接受衰老细胞溶解药物（D+Q，n=6）或安慰剂（n=6）治疗。肥胖小鼠的卵巢中衰老细胞更多，p21 和 p16 以及脂褐素染色和巨噬细胞浸润增加表明这一点。用 D+Q 治疗可显著减少肥胖小鼠卵巢中衰老细胞的负担。肥胖或用 D+Q 治疗均未影响卵巢滤泡的数量。总之，我们的数据表明，由于瘦素缺乏引起的肥胖会增加卵巢中衰老细胞的负荷，而衰老细胞溶解药物治疗可减少这种负荷。但是，肥胖或 D+Q 治疗均未影响卵巢储备。
