DNA methylation variations and epigenetic aging in telomere biology disorders

被引：5

作者：

Carlund, Olivia ^{[1
]}

Norberg, Anna ^{[2
]}

Osterman, Pia ^{[1
]}

Landfors, Mattias ^{[1
]}

Degerman, Sofie ^{[1
,3
]}

Hultdin, Magnus ^{[1
]}

机构：

[1] Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden

[2] Umea Univ, Dept Med Biosci, Med & Clin Genet, Umea, Sweden

[3] Umea Univ, Dept Clin Microbiol, Umea, Sweden

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

LENGTH; LYMPHOCYTES; MUTATIONS; CLOCK; GENE; AGE;

D O I：

10.1038/s41598-023-34922-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Telomere Biology Disorders (TBDs) are characterized by mutations in telomere-related genes leading to short telomeres and premature aging but with no strict correlation between telomere length and disease severity. Epigenetic alterations are also markers of aging and we aimed to evaluate whether DNA methylation (DNAm) could be part of the pathogenesis of TBDs. In blood from 35 TBD cases, genome-wide DNAm were analyzed and the cases were grouped based on relative telomere length (RTL): short (S), with RTL close to normal controls, and extremely short (ES). TBD cases had increased epigenetic age and DNAm alterations were most prominent in the ES-RTL group. Thus, the differentially methylated (DM) CpG sites could be markers of short telomeres but could also be one of the mechanisms contributing to disease phenotype since DNAm alterations were observed in symptomatic, but not asymptomatic, cases with S-RTL. Furthermore, two or more DM-CpGs were identified in four genes previously linked to TBD or telomere length (PRDM8, SMC4, VARS, and WNT6) and in three genes that were novel in telomere biology (MAS1L, NAV2, and TM4FS1). The DM-CpGs in these genes could be markers of aging in hematological cells, but they could also be of relevance for the progression of TBD.

引用

页数：12

共 62 条

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