Mitochondrial Impairment Mechanism in D-galactose-induced Senescence in Experimental Fibroblast Cell Model

To establish an effective model for cellular senescence, human embryo lung fibroblast cells (MRC-5) were cultured in D-galactose (D-Gal) medium respectively, as cont rol, same concentration of D-glucose (D-Glu) was used. Decrease in cell proliferation, increase in senescence associated β-galactosidase activity, up-expression of p21 protein, and cell cycle arrest at S-phage were observed in D-Gal-treated cells. Meanwhile, D-Gal-treated cells showed the significant increased ROS and MDA level and decreased SOD activity. Furthermore, mitochondrial impairment and decrease in efficiency of oxidative phosphorylation (OXPHOS) was induced by D-Gal as evidenced by the decreased transmembrane potential, reduction of ATP production and change s of respiration function. Additionally, the significant decrease of mitochondrial quantity, mitochondrial DNA (mtDNA) copy number and increased mtDNA damage were detected in D-Gal-treated cells. Our data demonstrate that D-Gal induces mitochondrial oxidative impairment associated with increased generation of ROS, ultimately inhibiting the ATP synthesis which contributes to premature cellular senescence.