Pharmacology and Toxicology Laboratory, Food & Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India.
Food & Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India.
Probiotics Antimicrob Proteins. 2020 Jun;12(2):563-576. doi: 10.1007/s12602-019-09576-z.
Information regarding cellular anti-senescence attributes of probiotic bacteria vis-à-vis modulation of senescence-associated secretory phenotype (SASP) and mTOR signaling is very limited. The present study assessed anti-senescence potential of secretory metabolites of probiotic Lactobacillus fermentum (Lact. fermentum) using HO-induced model of senescence in 3T3-L1 preadipocytes. Application of HO-induced cellular senescence characterized by increased cell size and SA-β-gal activity, activation of SASP and reactive oxygen species (ROS), DNA damage response and induction of cell cycle inhibitors (p53/p21/p16). Further, a robust stimulation of the PI3K/Akt/mTOR pathway and AMPK signaling was also observed in HO-treated cells. However, exposure of cells to cell-free supernatant of Lact. fermentum significantly attenuated phosphorylation of PI3K/Akt/mTOR pathway and alleviated senescence markers p53, p21, SA-β-gal, p38MAPK, iNOS, cox-2, ROS, NF-κB, and DNA damage response. These results provide evidence that secretory metabolites of Lact. fermentum can mitigate the development as well as severity of stress-induced senescence thereby indicating its utility for use as anti-aging or age-delaying agent.
关于益生菌细菌的细胞抗衰老特性的信息，以及对衰老相关分泌表型（SASP）和 mTOR 信号的调节作用的信息非常有限。本研究使用 3T3-L1 前脂肪细胞中的 HO 诱导的衰老模型，评估了益生菌发酵乳杆菌（Lact. fermentum）分泌代谢物的抗衰老潜力。HO 诱导的细胞衰老的应用特征为细胞体积增大和 SA-β-半乳糖酶活性增加、SASP 和活性氧（ROS）的激活、DNA 损伤反应和细胞周期抑制剂（p53/p21/p16）的诱导。此外，还观察到 HO 处理细胞中 PI3K/Akt/mTOR 途径和 AMPK 信号的强烈刺激。然而，细胞暴露于发酵乳杆菌的无细胞上清液中可显著减弱 PI3K/Akt/mTOR 途径的磷酸化，并减轻衰老标志物 p53、p21、SA-β-半乳糖酶、p38MAPK、iNOS、cox-2、ROS、NF-κB 和 DNA 损伤反应。这些结果表明，发酵乳杆菌的分泌代谢物可以减轻应激诱导的衰老的发展和严重程度，从而表明其作为抗衰老或延缓衰老剂的用途。
