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轻度认知障碍与老年人基因组中核糖体基因的低拷贝数有关。

Mild cognitive impairment is associated with low copy number of ribosomal genes in the genomes of elderly people.

作者信息

Veiko Natalia N, Ershova Elizaveta S, Veiko Roman V, Umriukhin Pavel E, Kurmyshev Marat V, Kostyuk Georg P, Kutsev Sergey I, Kostyuk Svetlana V

机构信息

Research Centre for Medical Genetics (RCMG), Moscow, Russia.

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A. Negovsky Research Institute of General Reanimatology, Moscow, Russia.

出版信息

Front Genet. 2022 Sep 19;13:967448. doi: 10.3389/fgene.2022.967448. eCollection 2022.

Abstract

: Mild cognitive impairments (MCI) accompanying aging are associated with oxidative stress. The ability of cells to respond to stress is determined by the protein synthesis level, which depends on the ribosomes number. Ribosomal deficit was documented in MCI. The number of ribosomes depends, together with other factors, on the number of ribosomal genes copies. We hypothesized that MCI is associated with low rDNA CN in the elderly person genome. rDNA CN and the telomere repeat (TR) content were determined in the DNA of peripheral blood leukocytes of 93 elderly people (61-91 years old) with MCI and 365 healthy volunteers (16-91 years old). The method of non-radioactive quantitative hybridization of DNA with biotinylated DNA probes was used for the analysis. In the MCI group, rDNA CN (mean 329 ± 60; median 314 copies, = 93) was significantly reduced ( < 10) compared to controls of the same age with preserved cognitive functions (mean 412 ± 79; median 401 copies, = 168) and younger (16-60 years) control group (mean 426 ± 109; median 416 copies, = 197). MCI is also associated with a decrease in TR DNA content. There is no correlation between the content of rDNA and TR in DNA, however, in the group of DNA samples with rDNA CN > 540, TR content range was significantly narrowed compared to the rest of the sample. Mild cognitive impairment is associated with low ribosomal genes copies in the elderly people genomes. A low level of rDNA CN may be one of the causes of ribosomal deficit that was documented in MCI. The potential possibilities of using the rDNA CN indicator as a prognostic marker characterizing human life expectancy are discussed.

摘要

衰老伴随的轻度认知障碍(MCI)与氧化应激有关。细胞对应激的反应能力由蛋白质合成水平决定,而蛋白质合成水平取决于核糖体数量。在MCI中已记录到核糖体缺陷。核糖体数量与其他因素一起,取决于核糖体基因拷贝数。我们假设MCI与老年人基因组中低核糖体DNA拷贝数(rDNA CN)有关。测定了93名患有MCI的老年人(61 - 91岁)和365名健康志愿者(16 - 91岁)外周血白细胞DNA中的rDNA CN和端粒重复序列(TR)含量。采用生物素化DNA探针与DNA进行非放射性定量杂交的方法进行分析。在MCI组中,与认知功能正常的同龄对照组(平均412±79;中位数401拷贝,n = 168)和年轻(16 - 60岁)对照组(平均426±109;中位数416拷贝,n = 197)相比,rDNA CN(平均329±60;中位数314拷贝,n = 93)显著降低(p < 0.01)。MCI还与TR DNA含量降低有关。DNA中rDNA和TR的含量之间没有相关性,然而,在rDNA CN > 540的DNA样本组中,TR含量范围与其余样本相比显著变窄。轻度认知障碍与老年人基因组中低核糖体基因拷贝数有关。低水平的rDNA CN可能是MCI中记录到的核糖体缺陷的原因之一。讨论了将rDNA CN指标用作表征人类预期寿命的预后标志物的潜在可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a33/9527325/2cd5dfc2b7bf/fgene-13-967448-g001.jpg

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