Research Paper|Volume 17, Issue 9|pp 2410—2429

Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles

Jessica Louzame Ruano¹, Leire Bejarano¹, Rosa Serrano¹, Ruth Alvarez Diaz², Juana Maria Flores³, Ana Cayuela López⁴, Maria A. Blasco¹

¹Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
²Bioinformatics Unit, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
³Animal Surgery and Medicine Department, Faculty of Veterinary Science, Complutense University of Madrid, Madrid, Spain
⁴Confocal Microscopy Unit, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain

* Present address: University of Lausanne, Switzerland

Received: October 21, 2024Accepted: August 18, 2025Published: September 17, 2025

https://doi.org/10.18632/aging.206320

Copyright: © 2025 Louzame et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

TRF1, a component of the telomere shelterin complex, plays crucial roles in telomere protection, telomere length regulation, and stemness. Here, we describe a previously unknown connection between TRF1 and metabolism. Telomere attrition has been linked to obesity. Our study reveals that Trf1-deficient mice exhibit a leaner phenotype, reduced adiposity, and improved glucose tolerance, even when subjected to a high-fat diet, independently of telomere shortening. These findings uncover a previously unknown role of TRF1 in regulating metabolism.