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Utilizing TERRA-capture RNA-seq and Oxford Nanopore direct RNA sequencing to acquire full-length TERRA, we annotate TERRA transcription regions in the human T2T-CHM13 reference genome. TERRA transcripts encompass hundreds to over a thousand nucleotides of telomeric repeats, predominantly originating from 61\u201329-37 bp repeat promoters enriched with H3K4me3, RNA Pol II, CTCF, and R-loops. We develop a bioinformatics tool, TERRA-QUANT, for quantifying TERRA using RNA-seq datasets and find that TERRA increases with age in blood, brain, and fibroblasts. TERRA upregulation in aged leukocytes is confirmed by reverse transcription quantitative polymerase chain reaction. Single-cell RNA-seq analysis demonstrates TERRA expression across various cell types, with upregulation observed in neurons during human embryonic stem cell differentiation. Additionally, TERRA levels are elevated in brain cells in the early stage of Alzheimer\u2019s disease. Our study provides evidence linking TERRA to human aging and diseases.<\/jats:p>","DOI":"10.1093\/nar\/gkaf597","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:46:36Z","timestamp":1749714396000},"source":"Crossref","is-referenced-by-count":13,"title":["Telomeric repeat-containing RNA increases in aged human cells"],"prefix":"10.1093","volume":"53","author":[{"given":"Yu-Hung","family":"Hsieh","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Taiwan University , No.\u00a01 Sec. 4 Roosevelt Road , Taipei 10617 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Hua","family":"Tai","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Taiwan University , No.\u00a01 Sec. 4 Roosevelt Road , Taipei 10617 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ting","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Taiwan University , No.\u00a01 Sec. 4 Roosevelt Road , Taipei 10617 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Taiwan University , No.\u00a01 Sec. 4 Roosevelt Road , Taipei 10617 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7247-4558","authenticated-orcid":false,"given":"Po-Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Taiwan University , No.\u00a01 Sec. 4 Roosevelt Road , Taipei 10617 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