Armeli Federica, Mengoni Beatrice, Schifano Emily, Lenz Thomas, Archer Trevor, Uccelletti Daniela, Businaro Rita
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
Department of Human Sciences, European University of Rome, 00163 Rome, Italy.
Antioxidants (Basel). 2025 Mar 27;14(4):393. doi: 10.3390/antiox14040393.
Autophagy, a catabolic process essential for maintaining cellular homeostasis, declines with age and unhealthy lifestyles, contributing to neurodegenerative diseases. Probiotics, including Milmed yeast, have demonstrated anti-inflammatory and antioxidant properties. This study evaluated the activity of Milmed on BV-2 microglial cells in vitro and in the in vivo model of () in restoring autophagic processes. BV-2 microglial cells were incubated with (Milmed treated yeast or untreated yeast) and then stimulated with lipopolysaccharide (LPS). mRNAs of the autophagic factors and antioxidant enzymes were assessed by qPCR; mTOR and NRF2 were evaluated by ELISA. pNRF2 compared with cytosolic NRF2 was evaluated by immunofluorescence. The longevity, body size, and reactive oxygen species (ROS) levels of were measured by fluorescence microscopy. Treatment with Milmed YPD cultured yeast or the dried powder obtained from it promoted autophagic flux, as shown by the increased expression of the , , , and mRNAs and the inhibition of mTOR, as evaluated by ELISA. It also enhanced the antioxidant response by increasing the expression of , , and ; moreover, pNRF2 expression compared with cytosolic NRF2 expression was enhanced, as shown by immunofluorescence. Milmed dietary supplementation prolonged the survival of and reduced the age-related ROS accumulation without changing the expression of The pro-longevity effect was found to be dependent on SKN-1/Nrf2 activation, as shown by the absence of benefit in mutants. Milmed yeast demonstrates significant pro-autophagy and antioxidant activity with significant pro-longevity effects in , thereby extending the lifespan and improving stress resistance, which, together with the previously demonstrated anti-inflammatory activity, highlights its role as a highly effective probiotic for its beneficial health effects. Activation of the SKN-1/NRF2 pathway and the modulation of autophagy support the therapeutic potential of Milmed in neuroprotection and healthy aging.
自噬是维持细胞内稳态所必需的分解代谢过程，会随着年龄增长和不健康的生活方式而下降，进而导致神经退行性疾病。包括米尔梅德酵母在内的益生菌已显示出抗炎和抗氧化特性。本研究评估了米尔梅德在体外BV-2小胶质细胞以及在体内（）模型中恢复自噬过程的活性。将BV-2小胶质细胞与（米尔梅德处理过的酵母或未处理的酵母）孵育，然后用脂多糖（LPS）刺激。通过qPCR评估自噬因子和抗氧化酶的mRNA；通过ELISA评估mTOR和NRF2。通过免疫荧光评估与细胞溶质NRF2相比的pNRF2。通过荧光显微镜测量（）的寿命、体型和活性氧（ROS）水平。用米尔梅德YPD培养的酵母或从中获得的干粉处理可促进自噬通量，这通过ELISA评估的、、、和mRNA表达增加以及mTOR的抑制得以体现。它还通过增加、和的表达增强了抗氧化反应；此外，如免疫荧光所示，与细胞溶质NRF2表达相比，pNRF2表达增强。米尔梅德膳食补充剂延长了（）的存活时间并减少了与年龄相关的ROS积累，而不改变（）的表达。发现延寿作用依赖于SKN-1/Nrf2激活，如在（）突变体中无益处所示。米尔梅德酵母在（）中表现出显著的促自噬和抗氧化活性以及显著的延寿作用，从而延长了寿命并提高了抗应激能力，这与先前证明的抗炎活性一起，突出了其作为具有有益健康作用的高效益生菌的作用。SKN-1/NRF2途径的激活和自噬的调节支持了米尔梅德在神经保护和健康衰老方面的治疗潜力。
Zotero 插件
