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Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis. Curcumin, a natural phenol, possesses antioxidant and anti-inflammatory properties. However, the effect of curcumin on endothelial senescence is unclear. This study explores the effect of curcumin on hydrogen peroxide (H 2 O 2 )-induced endothelial premature senescence and the mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured, and premature senescence was induced with 100 µM H 2 O 2 . Results showed that pretreatment with curcumin significantly attenuated the H 2 O 2 -induced HUVECs' premature senescence, which was evidenced by a decreased percentage of senescence-associated β-galactosidase positive cells, improved cell division and decreased expression of senescence-associated protein p21 (all p<0.05). Pretreatment with curcumin decreased oxidative stress and apoptosis in H 2 O 2 -treated HUVECs. Treatment of HUVECs with H 2 O 2 also down-regulated the phosphorylation of endothelial nitric oxide synthase (eNOS), decreased the level of nitric oxide in the culture medium, and inhibited the protein expression and enzymatic activity of silent information regulator 1 (SIRT1), while pretreatment with curcumin partly reversed these effects (all p<0.05). Treatment with curcumin alone enhanced the enzymatic activity of SIRT1, but didn't affect cellular senescence, cell growth or apoptosis compared to the Control. The inhibition of SIRT1 using SIRT1 short interfering RNA (siRNA) could decrease the expression and phosphorylation of eNOS and abrogate the protective effect of curcumin on H 2 O 2 -induced premature senescence. These findings suggest that curcumin could attenuate oxidative stress-induced HUVECs' premature senescence via the activation of SIRT1.Key words curcumin; endothelial senescence; silent information regulator 1 (SIRT1); hydrogen peroxide Cellular senescence is defined as an irreversible state of growth arrest and accompanied by a specific set of phenotypic changes, gene expression and cell function.1) It has been realized that senescence is induced by a variety of insults, including those causing intracellular oxidative stress, such as hydrogen peroxide (H 2 O 2 ).2) This kind of cellular senescence is called the stress-induced premature senescence (SIPS). Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis.3) Human studies showed that there were vascular cells exhibiting the morphological features of cellular senescence. [4][5][6] Silent information regulator 1 (SIRT1) is a member of the sirtuin family of proteins, which are homologs of the Sir2 gene in Saccharomyces (S.) cerevisiae. SIRT1 has been known as an oxidized form of nicotinamide adenine dinucleotide (NAD + )-dependent class III histone deacetylase (HDAC) and plays a key role in regulating cellular senescence, cell survival and metabolism through deacetylation of various histones and non-histone substrates.7,8) SIRT1 is highly expressed in the vasculature. A gro...