IGFBP-3 plays an important role in senescence as an aging marker

Aging study requires aging markers to measure the degree of aging process. The aging markers such as senescence associated-β-galactosidase (SA-β-gal), lipofuscin, telomere, p53 and p16 have been known in aging study until now. Therefore, we investigated the role of genes and proteins related to aging in young, senescent and H₂O₂-induced old cells to develop a novel aging marker involved in aging mechanism. After cellular aging was compared in young, senescent and H₂O₂-induced old cells using SA-β-galactosidase staining assay, the expression level of genes and proteins in senescent and H₂O₂-induced old cells were compared and analyzed with those of young cells using RT-PCR, western blot and immunofluorescence staining. First of all, the senescent cells and the cells aged by H₂O₂ showed higher level of SA-β-galactosidase staining than young cells. In particular, the expression level of IGFBP-3 was decreased in senescent and H₂O₂-induced old cells compared with young cells. Moreover, the senescent and H2O2-induced old cells showed higher expression levels of p-PI3K, Akt-1, p-mTOR, p-FoxO1 and FoxO1 than young cells. Furthermore, the expression levels of p300, Ac-p53, p53, p-p21 and p16 were significantly increased in senescent and H₂O₂-induced cells compared to young cells. However, the expression level of SIRT-1 was decreased in senescent and H₂O₂-induced old cells compared to young cells. In conclusion, IGFBP-3 up-regulates PI3K/Akt/mTOR signaling pathway and down-regulates autophagy during cell aging. These results suggest that IGFBP-3 could play a key role in aging study as an important aging marker.