全新发现“垃圾DNA”序列在衰老、癌症中的潜在作用

2021-07-24 Sunny MedSci原创

人体基本上由数万亿个活细胞组成。它随着细胞老化而老化,当这些细胞最终停止复制和分裂时就会发生老化。

人体基本上由数万亿个活细胞组成。它随着细胞老化而老化,当这些细胞最终停止复制和分裂时就会发生老化。科学家们早就知道基因会影响细胞的衰老方式和人类的寿命,但它究竟是如何运作的仍不清楚。由华盛顿州立大学的研究人员领导的一项新研究的发现解决了这个难题的一小部分,使科学家离解开衰老之谜又近了一步。

由药学院教授朱继悦领导的研究小组最近发现了一个名为VNTR2-1的DNA区域,该区域似乎可以驱动端粒酶基因的活性,该基因已被证明可以防止某些类型的衰老细胞。该研究发表在美国国家科学院院刊( PNAS ) 上。

Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene.Proceedings of the National Academy of Sciences Jun 2021, 118 (26) e2019043118; DOI: 10.1073/pnas.2019043118

端粒酶基因控制端粒酶的活性,端粒酶有助于产生端粒,端粒是每条DNA链末端的帽,保护细胞内的染色体。在正常细胞中,每次细胞在分裂之前复制它们的DNA时,端粒的长度都会变短一点。当端粒太短时,细胞就不能再繁殖,导致它们老化和死亡。然而,在某些细胞类型中——包括生殖细胞和癌细胞——端粒酶基因的活性确保端粒在DNA复制时重置为相同的长度。这本质上是重新启动新后代衰老时钟的原因,但也是癌细胞可以继续繁殖并形成肿瘤的原因。

了解端粒酶基因是如何被调节和激活的,以及为什么它只在某些类型的细胞中活跃,有一天可能成为了解人类如何衰老以及如何阻止癌症扩散的关键。这就是为什么朱在过去20年的科学家职业生涯中一直专注于研究这种基因的原因。

朱说,他的团队最新发现VNTR2-1有助于驱动端粒酶基因的活性,这一发现尤其值得注意,因为它代表的DNA序列类型。

“我们基因组的近50%由不编码蛋白质的重复DNA组成,”朱说。“这些 DNA 序列往往被认为是我们基因组中的‘垃圾 DNA’或暗物质,它们很难研究。我们的研究描述了其中一个单元实际上具有增强端粒酶基因活性的功能。 ”

他们的发现基于一系列实验,这些实验发现从癌细胞中删除DNA序列——无论是在人类细胞系还是小鼠中——都会导致端粒缩短、细胞老化和肿瘤停止生长。随后,他们进行了一项研究,研究了乔治亚州百岁老人研究中白人和非裔美国百岁老人以及对照组参与者的DNA 样本中的序列长度,该研究对1988年至2008年间的100岁或以上人群进行了跟踪研究。研究人员发现,该序列的长度从DNA的53次重复或拷贝到160次重复不等。

“它变化很大,我们的研究实际上表明,端粒酶基因在序列较长的人中更活跃,”朱说。

由于仅在非裔美国人参与者中发现了非常短的序列,他们更仔细地观察了该组,发现与对照组参与者相比,具有短VNTR2-1序列的百岁老人相对较少。然而,朱说值得注意的是,序列较短并不一定意味着你的寿命会更短,因为这意味着端粒酶基因不太活跃,你的端粒长度可能更短,这可能会降低你患癌症的可能性。

“我们的研究结果告诉我们,这个VNTR2-1序列有助于我们衰老和我们如何患癌症的遗传多样性,”朱说。“我们知道致癌基因——或癌症基因——和肿瘤抑制基因并不能解释我们患癌症的所有原因。我们的研究表明,情况比致癌基因的突变要复杂得多,并且会产生强大的影响。扩大我们的研究范围以更仔细地研究这种所谓的垃圾DNA。”

朱指出,由于非裔美国人世代居住在美国,他们中的许多人都有白人祖先,他们可能从他们那里继承了一些这个序列。因此,下一步,他和他的团队希望能够在非洲人群中研究该序列。

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    2022-05-18 hxzhang
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    2021-12-02 cardio

    学习了

    0

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    2021-07-25 452946589

    学习了,谢谢

    0

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    2021-07-24 @gxl

    非常受用

    0

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    2021-07-24 Drfaith

    很棒的文章

    0

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    2021-07-24 医鸣惊人

    认真学习了

    0