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Science:端粒长度与性别、种族和慢性病相关,且因人体组织类型而异!

2020-09-17 王木木 生物探索

端粒是在染色体末端发现的重复的非编码DNA序列,就像保护帽一样,可以保护染色体末端免于降解和融合,使重要的遗传信息不致丢失。随着细胞的不断分裂,端粒长度(TL)会随时间逐渐缩短,最终触发细胞衰老。

端粒是在染色体末端发现的重复的非编码DNA序列,就像保护帽一样,可以保护染色体末端免于降解和融合,使重要的遗传信息不致丢失。随着细胞的不断分裂,端粒长度(TL)会随时间逐渐缩短,最终触发细胞衰老,因此TL长期以来也一直被认为是人类衰老和疾病的重要生物标志物。

正常衰老与端粒缩短有关,而端粒缩短与死亡率和与年龄有关的疾病相关。但端粒缩短,衰老与疾病之间的关系目前仍不完全清楚,且由于有关端粒长度与健康之间关系的大多数研究仅在血液中进行,因此也存在一个问题,血细胞中的端粒是否可以替代其他组织中的?

近日,来自美国芝加哥大学的研究人员通过对952个个体的共6000多种不同组织的端粒长度进行检测,发现遗传变异影响多种组织类型中的TL,全血中的TL具有足够的代表性,且TL与年龄、种族、性别等,以及慢性疾病的发生风险相关。相关研究结果于9月11日发表在《Science》上。

研究人员测量并使用Luminex分析了952名基因型组织表达(GTEx)项目捐赠者(已故,年龄20至70岁)的25种组织类型中的相对TL(RTL,相对于标准样品的端粒重复丰度)。之后使用线性混合模型分析了RTL和年龄、性别、民族等协变量之间的关系,对TL变异的来源,年龄、组织类型与TL之间的关系以及TL的生物学决定因素和相关性进行了研究,并对全血TL能否作为其他组织类型TL的替代物进行了评估。

人体组织中的TL

对各种人类组织类型中的TL分析表明,RTL在全血中最短,在睾丸中最长,组织RTL可分为三个聚类:中胚层和外胚层(如肌肉和皮肤)、内胚层起源的组织(如胃和肺)以及甲状腺和脑小脑。而这种组织类型中TL的差异可能是由于整个组织的内在因素(细胞分裂率和病史等)和外在因素(对环境暴露的响应)变化而导致的。

TLs在不同的人体组织类型之间存在差异,但在不同的组织类型之间存在相关性

研究还发现,全血的RTL与23种组织类型中的15种组织特异性RTL呈正相关性,这也表明全血中的TL可以代表许多组织类型中TL。此外,TL在个体间也各不相同,相比男性,女性的端粒更长;种族方面,非洲血统的个体在许多组织类型中具有更长的TL;BMI和吸烟状态也与较短的RTL相关;24个组织中,RTL与21种组织类型的年龄呈负相关性。

多数组织中年龄与TL呈负相关,在端粒较短的组织中相关性最强

研究人员检查了常见的与年龄相关的慢性疾病与组织内和跨组织的RTL之间的关联,发现2型糖尿病与所有组织的RTL较短以及胰腺RTL和冠状动脉RTL较短有关;多数慢性疾病与所有组织以及睾丸,冠状动脉,肾皮质和小脑的RTL缩短相关。但其未观察到RTL与癌症病史之间的任何关联。

文章的通讯作者Brandon L. Pierce说:“这些结果将有助于研究人员了解端粒长度的哪些方面是由于遗传所导致的,哪些方面可能会受到人们生活方式、环境暴露等的影响。反过来,这也将让科学家更容易研究和了解特定生物标记物在衰老和疾病中的作用 。”

原始出处:

Kathryn Demanelis, Farzana Jasmine, Lin S Chen,et al.Determinants of telomere length across human tissues.Science. 2020 Sep 11;369(6509):eaaz6876. doi: 10.1126/science.aaz6876.

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    2022-10-19 ms5000001410456216

    学习了

    0

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    2020-10-16 芹菜

    学习了

    0

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    2020-09-19 qjddjq
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    2020-09-19 jichang
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    2020-09-17 Baodongxu

    生命健康重要生物标志物

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