Streptococcus thermophilus CNCM I-5570 lysate counteracts the aging process in human dermal fibroblast cells by neutralizing harmful free radicals and impacting antioxidant and anti-inflammatory pathways, thus restoring their physiological functions

Previous studies have highlighted the in vitro and in vivo anti-aging potential of Streptococcus thermophilus prompting us to investigate the biomolecular mechanisms underlying its effects. We evaluated the reparative ability of S. thermophilus lysate in a hydrogen peroxide (H₂O₂)-induced senescence model of human dermal fibroblasts (HDFs). Cell proliferation, cell number, and senescence level were evaluated by IncuCyte® Live Cell Imager system, trypan blue dye exclusion test and β-galactosidase activity, respectively. We analyzed p21, prolyl 4-hydroxylase A1, intracellular collagen I, nuclear factor E2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB) and heme oxygenase-1 expression through western blot. Extracellular levels of collagen I, interleukin-1β, and IL-6 were assessed by ELISA. The oxidative stress markers were assayed using standard methods. The direct antioxidant activity of probiotic was quantified using multiple techniques. The presence of antioxidant genes in probiotic was detected via PCR assay. Probiotic lysate exposure increased the proliferation rate, counteracted the aging by reducing β-galactosidase activity and p21 levels, promoted collagen I synthesis and neutralized oxidative stress by activating Nrf2. The probiotic lysate inhibited the NF-κB pathway with pro-inflammatory marker downregulation. Notably, we revealed that probiotic exhibited strong free radical scavenging ability, iron-chelating properties, and significant ferric reducing power in a concentration-dependent manner. We identified seven genes with antioxidant function in its genome. Our results show that S. thermophilus lysate is efficacious in suppressing the biomolecular events associated with H₂O₂-induced cellular aging, thus supporting the reparative action of S. thermophilus, helpful in treating skin aging.