Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated β-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

中文翻译：

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神经酸抑制人沃顿胶源性间充质干细胞的复制衰老。

细胞衰老导致细胞周期停滞并促进增殖永久停止。由于间充质干细胞 (MSC) 的衰老会降低增殖和多能性并增加免疫原性，因此衰老的 MSC 不适合细胞治疗。因此，抑制MSCs的细胞衰老非常重要。最近有报道称代谢物可以控制衰老疾病。因此，我们的目的是鉴定调节 MSC 复制衰老的新代谢物。使用粪便代谢物库，我们确定神经酸（NA）作为复制衰老调节的候选代谢物。在复制性衰老 MSC 中，NA 减少了衰老相关的β-半乳糖苷酶阳性细胞、衰老相关基因的表达，并增加了干性和脂肪生成。此外，在非衰老的MSC中，NA处理延迟了连续传代培养引起的衰老并促进增殖。我们首次证实 NA 可以延迟和抑制细胞衰老。考虑到药物治疗的最佳浓度、持续时间和时机，NA是一种新型的潜在代谢物，可用于开发调节细胞衰老的技术。