Objective The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. Methods First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. Results In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. Conclusion Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.

HOU Yu Li;WANG Yi Fei;SONG Qiao;ZHANG Xiao Min;LIU Jing;WANG Ya Qi;CUI Yu Ting;FU Jing Xuan;FENG Zi Yi;ZHANG Chi;WANG Pei Chang

Department of Clinical Laboratory,Xuanwu Hospital,National Clinical Research Center for Geriatric Diseases,Capital Medical University,Beijing 100053,China;Clinical Laboratory Diagnostics,Capital Medical University,Beijing 100053,China

生物医学与环境科学（英文版）

[1]HOU Yu Li;WANG Yi Fei;SONG Qiao;ZHANG Xiao Min;LIU Jing;WANG Ya Qi;CUI Yu Ting;FU Jing Xuan;FENG Zi Yi;ZHANG Chi;WANG Pei Chang-.IGF-1 Accelerates Cell Aging by Inhibiting POLD1 Expression)[J].生物医学与环境科学（英文版）,2022(11):981-991,中插1

linsitinib

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