The Role of TERRA, a Long Non-Coding RNA, in Human Aging and Alzheimer's Disease

Researchers from National Taiwan University, Academia Sinica, and National Taiwan University Hospital have uncovered significant insights into the role of a specific long non-coding RNA called TERRA (Telomeric Repeat-Containing RNA) in human aging and neurodegenerative conditions such as Alzheimer's disease. Their groundbreaking study, recently published in Nucleic Acids Research, highlights TERRA's potential as a biomarker for age-related and neurodegenerative diseases.

TERRA originates from telomeres—the protective end-caps of chromosomes—and consists of repetitive UUAGGG sequences along with unique subtelomeric regions. Although TERRA is known for its involvement in telomere maintenance, its precise function in aging processes has remained unclear due to the technical challenges of studying such repetitive sequences. To overcome this, the research team utilized Oxford Nanopore direct RNA sequencing and the complete T2T-CHM13 human genome reference, enabling comprehensive mapping and annotation of TERRA transcription across all chromosome ends.

They also developed TERRA-QUANT, a computational tool designed to analyze TERRA levels from various RNA sequencing datasets, including single-cell data from different human tissues. Their analyses revealed that TERRA levels increase significantly with age in tissues like blood, the brain, and fibroblasts. Moreover, dysregulated TERRA expression was observed in fibroblasts of patients with Hutchinson-Gilford Progeria Syndrome (HGPS), a condition characterized by premature aging. Notably, single-cell data indicated elevated TERRA levels in neurons derived from embryonic stem cells and during early stages of Alzheimer’s disease.

The team validated these findings through RT-qPCR experiments, confirming increased TERRA expression in aged blood cells and neurons from Alzheimer’s patients. Lead investigator Dr. Hsueh-Ping Catherine Chu emphasizes that TERRA might serve not only as an aging marker but also potentially play a functional role in the development of age-related diseases.

This pioneering research establishes a connection between TERRA expression and aging-related neurodegeneration, providing a new framework for future studies aimed at understanding and monitoring these conditions more effectively.

Source: https://medicalxpress.com/news/2025-07-coding-rna-terra-human-aging.html