Changes of the expression for genes related with senescence and the telomerase activity during cellular replicative and premature senescence in human embryonic lung fibroblasts

Abstract

Objective: To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro. Methods: The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H(2)O(2)(premature senescence, PS). The telomerase activity was detected by ELISA assay during cellular replicative and premature senescence. The mRNA level of oxidative stress responsive genes related with senescence for Foxo1, Foxo3, Pdx1, apoA-I and MMP1 was per-formed by RT-Q-PCR separately. Results: The mRNA level for Foxo1, Foxo3, apoA-I and Pdx1 was decreased separately during cellular replicative senescence compared to that in the young-stage cells with statistical signifi-cance (P<0.05). The expression of MMP1 was up-regulated 5.1-fold obviously (P<0.05). In premature senes-cence, the mRNA level was only decreased for Foxo1, Foxo3 and apoA-I, but up-regulated 2.3-fold and 6.2-fold for Pdx1 and MMP1 respcetively vs 22PDL significantly (P<0.05). The telomerase activity in young cells was not detected, and it increased in mid-aged cells and replicative senescence stages during cellular replicative se-nescence as compared to 22PDL with statistical significance (P<0.05). The telomerase activity in premature se-nescence was highly active. Conclusion: The expression for genes related with senescence has differences be-tween replicative and premature senescence and hydrogen peroxide modifies their expression levels. The telomer-ase activity has been going up with increased PDLs.