Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression
Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression
复制标题
小檗碱通过调节 p16 和细胞周期蛋白表达改善细胞衰老并延长小鼠寿命
DOI：
10.1111/acel.13060
复制
发表时间：
2019-11-26
期刊：
影响因子：
7.8
通讯作者：
Xie, Zhengwei
中科院分区：
文献类型：
--
作者：
Dang, Yao;An, Yongpan;Xie, Zhengwei
尽管在过去的几十年里，人们对衰老和衰老进行了广泛的研究，但临床上还缺乏抗衰老的治疗方法。这项研究介绍了黄连素(BBR)对衰老过程的影响，从而有望延长模式生物的寿命。BBR延长了人胎肺二倍体成纤维细胞(2BS和WI38)的复制寿命，改善了细胞形态，并增强了复制衰老的返老性标志物。BBR还通过晚期种群倍增(PD)挽救了衰老细胞。此外，在含BBR的培养液中生长的晚期PD细胞的衰老相关β-半乳糖苷酶(SA-β-GAL)阳性细胞率比对照细胞低72%，其形态与年轻细胞相似。从机制上讲，BBR通过促进细胞周期从G(0)或G(1)期进入S/G(2)-M期，从而促进细胞的生长和增殖。最重要的是，BBR将化疗小鼠和自然衰老小鼠的寿命分别延长了52%和16.49%。自然衰老小鼠的剩余寿命延长了80%，从85.5天延长到154天。口服BBR可显著改善小鼠的健康寿命、皮毛密度和行为活动。因此，BBR可能是开发抗衰老药物的理想候选者。
Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti-aging. This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts (2BS and WI38). BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence-associated beta-galactosidase (SA-beta-gal)-positive cell rates of late PD cells grown in the BBR-containing medium were similar to 72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically, BBR improved cell growth and proliferation by promoting entry of cell cycles from the G(0) or G(1) phase to S/G(2)-M phase. Most importantly, BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by similar to 52% and similar to 16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.