Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H 2 O 2 -Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes.

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 H ₂ O ₂ -induced model of senescence in 3T3-L1 preadipocytes. Application of H ₂ O ₂ -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 ^WAF1 /p16 ^INK4a ). Further, a robust stimulation of the PI3K/Akt/mTOR pathway and AMPK signaling was also observed in H ₂ O ₂ -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 ^WAF1 , 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.