A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress‐induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the over‐expression of NAMPT, which is the rate‐limiting enzyme in mammalian NAD⁺ salvage pathway, delays replicative senescence in vitro. However, whether Nampt‐overexpressing cells are tolerant of stress‐induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt‐overexpressing transgenic mice (Nampt Tg‐MEF cells) possess resistance against stress‐induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg‐MEF cells compared to wild‐type cells. Moreover, we found that Nampt Tg‐MEF cells show acute expression of unfolded protein response (UPR)‐related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD⁺ axis functions to protect cells not only from replicative senescence, but also from stress‐induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD⁺ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging.

中文翻译：

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烟酰胺磷酸核糖基转移酶在小鼠细胞中的过量表达赋予抗氧化和内质网应激诱导的早衰的保护作用。

衰老生物的主要特征是衰老细胞的积累。衰老的生物体中积累的衰老细胞，特别是应激诱导的衰老细胞，导致组织的再生潜力和功能下降。我们最近报道说，NAMPT的过度表达是哺乳动物NAD ⁺打捞途径中的限速酶，它会延迟体外复制衰老。但是，尚不清楚Nampt过表达的细胞是否能耐受应激诱导的过早衰老。在这里，我们显示了源自Nampt过表达的转基因小鼠（Nampt的原代小鼠胚胎成纤维细胞Tg-MEF细胞在体外具有抗应激诱导的早衰的能力。我们发现与野生型细胞相比，Nampt Tg-MEF细胞需要更高的氧化或内质网（ER）应力才能诱导过早衰老。此外，我们发现Nampt Tg-MEF细胞显示未折叠的蛋白反应（UPR）相关基因的急性表达，这反过来又有助于恢复蛋白稳态并避免细胞衰老。我们的结果表明NAMPT / NAD ⁺轴不仅可以保护细胞免受复制性衰老，而且还可以保护细胞免受应激诱导的过早衰老。我们预计体内NAMPT活性的激活或NAD ^+的增加 可以保护组织免于过早衰老细胞的积累，从而保持健康的衰老。