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父母的遗传学与宫内环境相互作用,重新编程新生儿的端粒和免疫。

Parental Genetics Communicate with Intrauterine Environment to Reprogram Newborn Telomeres and Immunity.

机构信息

Department Biochemistry, Ziauddin University, Karachi 74600, Pakistan.

Department Gynecology and Obstetrics, Ziauddin University, Karachi 74600, Pakistan.

出版信息

Cells. 2022 Nov 25;11(23):3777. doi: 10.3390/cells11233777.

Abstract

Telomeres, markers for cellular senescence, have been found substantially influenced by parental inheritance. It is well known that genomic stability is preserved by the DNA repair mechanism through telomerase. This study aimed to determine the association between parents−newborn telomere length (TL) and telomerase gene (TERT), highlighting DNA repair combined with TL/TERT polymorphism and immunosenescence of the triad. The mother−father−newborn triad blood samples (n = 312) were collected from Ziauddin Hospitals, Pakistan, between September 2021 and June 2022. The telomere length (T/S ratio) was quantified by qPCR, polymorphism was identified by Sanger sequencing, and immunosenescence by flow cytometry. The linear regression was applied to TL and gene association. The newborns had longest TL (2.51 ± 2.87) and strong positive association (R = 0.25, p ≤ 0.0001) (transgenerational health effects) with mothers’ TL (1.6 ± 2.00). Maternal demographics—socioeconomic status, education, and occupation—showed significant effects on TL of newborns (p < 0.015, 0.034, 0.04, respectively). The TERT risk genotype CC (rs2736100) was predominant in the triad (0.6, 0.5, 0.65, respectively) with a strong positive association with newborn TL (β = 2.91, <0.0011). Further analysis highlighted the expression of KLRG 1+ in T-cells with shorter TL but less frequent among newborns. The study concludes that TERT, parental TL, antenatal maternal health, and immunity have a significantly positive effect on the repair of newborn TL.

摘要

端粒是细胞衰老的标志物,其长度受到父母遗传的显著影响。众所周知,基因组稳定性通过端粒酶的 DNA 修复机制得以维持。本研究旨在确定父母-新生儿端粒长度 (TL) 和端粒酶基因 (TERT) 之间的关联,强调 DNA 修复与 TL/TERT 多态性和三联体的免疫衰老相结合。2021 年 9 月至 2022 年 6 月,从巴基斯坦 Ziauddin 医院采集了母亲-父亲-新生儿三联体血液样本(n = 312)。通过 qPCR 定量端粒长度(T/S 比),通过 Sanger 测序鉴定多态性,通过流式细胞术鉴定免疫衰老。应用线性回归分析 TL 和基因的关联。新生儿的端粒最长(2.51 ± 2.87),与母亲的端粒呈强烈正相关(R = 0.25,p ≤ 0.0001)(跨代健康影响)。母亲的人口统计学特征-社会经济地位、教育和职业-对新生儿的 TL 有显著影响(p < 0.015、0.034 和 0.04,分别)。TERT 风险基因型 CC(rs2736100)在三联体中占主导地位(0.6、0.5 和 0.65,分别),与新生儿 TL 呈强烈正相关(β = 2.91,<0.0011)。进一步的分析强调了较短 TL 的 T 细胞中 KLRG1+的表达,但在新生儿中较少见。该研究得出结论,TERT、父母 TL、产前母亲健康和免疫对新生儿 TL 的修复有显著的积极影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72df/9735452/7af17d550769/cells-11-03777-g001.jpg

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