The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation

Richard J. Acton, Wei Yuan, Fei Gao, Yudong Xia, Emma Bourne, Eva Wozniak, Jordana Bell, Karen Lillycrop, Jun Wang, Elaine Dennison, Nicholas C. Harvey, Charles A. Mein, Tim D. Spector, Pirro G. Hysi, Cyrus Cooper, Christopher G. Bell

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16-82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.

Original languageEnglish
Article number2655
Pages (from-to)2655
Number of pages1
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2021


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