Adjudin delays cellular senescence through Sirt3‑mediated attenuation of ROS production

Geng,Keyi; Fu,Ningzhen; Yang,Xiao; Xia,Weiliang

doi:10.3892/ijmm.2018.3917

Adjudin delays cellular senescence through Sirt3‑mediated attenuation of ROS production

Authors:
- Keyi Geng
- Ningzhen Fu
- Xiao Yang
- Weiliang Xia
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Affiliations: State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
Published online on: October 8, 2018 https://doi.org/10.3892/ijmm.2018.3917
Pages: 3522-3529

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Abstract

Aging, marked by the physical and functional decline in numerous biological processes, is associated with multiple pathologies including cancer, neurodegenerative diseases and cardiocerebral vascular diseases. The accumulation of reactive oxygen species (ROS) production is considered one of the major causes of aging‑associated diseases and a major therapeutic target. Hydroxyurea has been widely used for cellular senescence model. The expression level of cell cycle-related protein, ROS production and senescence-associated β-galactosidase are considered to be markers of cellular senescence. Strategies to slow senescence may be beneficial for various aging‑associated diseases. The results of the current study indicated that adjudin, a multi‑functional small molecule compound, delayed hydroxyurea‑induced senescence in mouse embryo fibroblasts (MEFs). Adjudin reduced the proportion of senescence‑associated β‑galactosidase‑positive cells and decreased the expression levels of senescence‑associated markers, p16 and p21. Mechanistically, adjudin exerted its anti‑senescence effect by elevating the expression level of sirtuin 3 (Sirt3), which attenuated ROS production through the regulation of forkhead box O3a and manganese superoxide dismutase expression. Furthermore, by comparing wild‑type and Sirt3‑knockout MEFs, it was demonstrated that Sirt3 mediated the anti‑senescence effect of adjudin. Taken together, the findings indicated that adjudin has anti‑aging properties that may be exploited to treat aging‑associated diseases.

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