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  • br Conclusion In this review we summarized the various


    Conclusion In this review, we summarized the various models commonly used in longevity and aging research, focusing on their genetic background, key findings, and their advantages/disadvantages in study of organismal (Table 3) and systemic aging (Table 4). These suggestions are helpful to select the suitable models to understand aging and longevity. In addition, we discussed about the evolutionary conservation of pathways associated with longevity, including Insulin signaling, mTOR, AMPK, and beta-adrenergic pathways. Among these, the beta-adrenergic system is mentioned to be the conserved pathway associated to longevity for the first time. Interestingly, all these conserved pathways link to 1196800-39-1 metabolism, suggesting that the energy control plays an essential role in longevity and aging. Supportively, caloric restriction is widely accepted intervention to prevent degenerative diseases and extend lifespan and/or healthspan [92,141,[153], [154], [155]]. Aging is an unescapable stage in life cycle. Like other stages, aging may be initiated programmatically (reversible), however, it becomes disordered (irreversible) at the end, which eventually leads to death. How these pathways function during these processes remains to be further investigated.
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    Acknowledgements This study was supported by grants from the National Basic Research Program of the Chinese Ministry of Science and Technology (973 Grants 2013CB530700 and 2007CB512103) and the National Natural Science Foundation of China (81630034 and 81130003) to Xiao-Li Tian.
    Introduction Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids and fibrous elements in the large arteries. The vascular endothelium is responsible for the regulation of vascular tone and the maintenance of vascular homeostasis [1,2]. Many studies have reported that alterations of endothelial function are early events in atherosclerosis development [3]. During the early stage of atherosclerosis, oxidized low-density lipoprotein (OxLDL) is known to enhance oxidative stress and inflammation, thereby inducing endothelial dysfunction and the formation of atherosclerotic plaques [4,5]. Numerous studies have demonstrated that OxLDL increases endothelial permeability and the expression of adhesion molecules that lead to anabatic adherence and the penetration of monocytes into the vascular endothelium [[6], [7], 1196800-39-1 [8]]. β‑catenin is a key modulator in the Wnt signaling pathway, which is involved in vasculogenesis, angiogenesis, intimal thickening and atherosclerosis [[9], [10], [11]]. β‑catenin associates with transcriptional T-cell factor/lymphocyte enhancing factor (TCF/LEF), thus regulating the coordination of cell-cell adhesion and the expression of numerous target genes, including cyclin D1, c-Myc and c-Jun. In recent years, several studies have reported that β‑catenin plays an important role in OxLDL-induced endothelial dysfunction [12,13]. Nevertheless, how OxLDL regulates the β‑catenin pathway remains unclear. As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells [14]. Under physiological conditions, NO is produced mainly from L-arginine by endothelial nitric oxide synthase (eNOS) in the endothelium of blood vessel walls [15]. Recently, eNOS has been demonstrated to interact directly with β‑catenin in endothelial cells, and eNOS activation leads to β‑catenin translocation to the nucleus with resultant effects on gene transcription and downstream functional responses [16]. These results indicate that the β‑catenin signaling pathway might rely on its interaction with eNOS and eNOS activity. Protein S-nitrosylation, the covalent modification of a protein cysteine thiol by an NO group to generate an S-nitrosothiol (SNO) [17], plays an important role in the progression of cardiovascular diseases [[18], [19], [20]]. eNOS can be S-nitrosylated in endothelial, cells and this modification reversibly attenuates enzyme activity. These studies have also identified zinc-tetrathiolate cysteine residues as the sites in eNOS that undergo S-nitrosylation in intact endothelial cells [[21], [22], [23]]. To our knowledge, the possibility that S-nitrosylation of cysteine residues on eNOS is involved in the modulation of its interaction with β‑catenin remains unexplored.