Cellular senescence is a stable cell cycle arrest induced by diverse triggers, including replicative exhaustion, DNA damaging agents, oncogene activation, oxidative stress, and chromatin disruption. With important roles in aging and tumor suppression, cellular senescence has been implicated also in tumor promotion. Here we show that certain multiwalled carbon nanotubes (MWCNTs), as fiber-like nanomaterials, can trigger cellular senescence in primary human mesothelial cells. Using in vitro approaches, we found manifestation of several markers of cellular senescence, especially after exposure to a long and straight MWCNT. These included inhibition of cell division, senescence-associated heterochromatin foci, senescence-associated distension of satellites, LMNB1 depletion, γH2A.X nuclear panstaining, and enlarged cells exhibiting senescence-associated β-galactosidase activity. Furthermore, genome-wide transcriptome analysis revealed many differentially expressed genes, among which were genes encoding for a senescence-associated secretory phenotype. Our results clearly demonstrate the potential of long and straight MWCNTs to induce premature cellular senescence. This finding may find relevance in risk assessment of workplace safety, and in evaluating MWCNT’s use in medicine such as drug carrier, due to exposure effects that might prompt onset of age-related diseases, or even carcinogenesis.

细胞衰老是由多种触发因素引起的稳定的细胞周期停滞，包括复制耗竭、DNA 损伤剂、癌基因激活、氧化应激和染色质破坏。细胞衰老在衰老和肿瘤抑制中发挥着重要作用，也与肿瘤的促进有关。在这里，我们证明某些多壁碳纳米管（MWCNT）作为纤维状纳米材料，可以引发原代人间皮细胞的细胞衰老。使用体外方法，我们发现了几种细胞衰老标志物的表现，特别是在暴露于长而直的多壁碳纳米管之后。这些包括抑制细胞分裂、衰老相关的异染色质灶、衰老相关的卫星扩张、LMNB1 耗竭、γH2A.X 核泛染色以及表现出衰老相关 β-半乳糖苷酶活性的细胞增大。此外，全基因组转录组分析揭示了许多差异表达的基因，其中包括编码衰老相关分泌表型的基因。我们的结果清楚地证明了长而直的多壁碳纳米管诱导细胞过早衰老的潜力。这一发现可能与工作场所安全风险评估以及评估多壁碳纳米管在药物载体等医学中的应用有关，因为暴露效应可能会促进与年龄相关的疾病的发生，甚至致癌。