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首页> 外文期刊>Cell cycle >Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity
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Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity

机译：衰老的人类成纤维细胞的睫状畸形损害了增殖能力

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摘要

Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence.
机译：有限次数的分裂无限期地阻止了它们的增殖之后，体细胞在培养中就会感觉到衰弱。 DNA损伤和衰老增加了中心体的细胞数量，中心体是确保双极有丝分裂纺锤体的2个微管组织中心。中心体还提供了初级纤毛从其延伸的基体，以感测和转导各种细胞外信号，特别是刺猬。暂时的细胞周期退出可通过细胞静止促进初级纤毛形成，但衰老对纤毛的影响尚不清楚。我们发现衰老的人类成纤维细胞增加了原发纤毛的频率和长度。衰老细胞中的负睫状调节因子CP110的水平降低，刺猬通路的关键元素水平也降低。刺猬抑制作用降低了年轻细胞的增殖，并伴随着细胞周期停滞而增加了纤毛长度，这暗示了刺猬在初级纤毛中的调节功能。年轻细胞群中CP110的消耗增加了纤化频率并减少了细胞增殖。这些数据表明原发纤毛可能是导致衰老的细胞增殖减少的新决定因素。

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