image: Figure 1. Depletion of Trf1 in mice induces weight loss. (A) Experimental plan: Trf1+/+ or Trf1lox/lox; hUBC-CreERT2 mice start to receive tamoxifen treatment intraperitoneally at 10 weeks of age until humane endpoint. (B) Weight follow-up in females (left) and males (right) in both genotypes. Note that TrfΔ/Δ females start to weigh less than wild-type at five months and males at six months. (C) Representative images of wild-type and Trf1 deleted mice of 10 months of age. Note the observable difference in weight and graying hair in Trf1Δ/Δ mice. (D) Measurement of body weight in 80-week-old mice. Note that the difference in weight is maintained throughout their lifespan. (E) Hematoxylin and eosin staining of liver, white and brown adipose tissue. Note that there are no differences between genotypes regarding liver and white adipose tissue. In brown adipose tissue, Trf1Δ/Δ mice present fewer and smaller lipid droplets than wild-type mice. Error bars, s.e.m.; only significant values are shown; *P < 0.05; **P < 0.01; ***P < 0.001 determined by two-tailed Student’s t-test (B, D)
Credit: 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.
“These findings uncover a previously unknown role of TRF1 in regulating metabolism.”
BUFFALO, NY — October 27, 2025 — A new research paper was published in Volume 17, Issue 9 of Aging-US on September 17, 2025, titled “Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.”
In this study led by first author Jessica Louzame Ruano and corresponding author Maria A. Blasco from the Spanish National Cancer Centre (CNIO), researchers investigated the role of TRF1, a protein known for protecting telomeres, in regulating whole-body metabolism. The results suggest that TRF1 influences metabolic health through mechanisms unrelated to its known function in telomere maintenance.
Obesity and metabolic disorders are major health concerns, especially as people age. To explore TRF1’s role beyond telomere protection, the research team studied both normal mice and genetically modified mice that lacked TRF1. Mice without TRF1 remained leaner over time, resisted fat accumulation, and showed healthier blood sugar and insulin levels compared to normal mice. Importantly, these benefits occurred without any detectable shortening of telomeres.
The leaner body composition in TRF1-deficient mice was not due to reduced food intake or increased physical activity. Instead, the fat loss appeared to result from biological changes in how energy was processed and stored. Male mice without TRF1 gained less weight and had lower LDL cholesterol levels, even on a high-fat diet. Female mice showed milder effects, reflecting known sex-based differences in susceptibility to diet-induced obesity. This highlights the importance of including both sexes in metabolic research.
“Major metabolic pathways related with energy production and regulation of metabolism homeostasis were also found downregulated in Trf1-deficient mice.”
Gene expression analysis in the liver revealed shifts in several key pathways. Genes related to fat production, energy generation, and muscle growth were downregulated, while genes linked to inflammation and cholesterol synthesis were upregulated. The mice also showed signs of higher energy expenditure and a shift from using fat to protein as an energy source, possibly due to their reduced fat reserves. However, some older mice developed mild liver stress, including fibrosis and DNA damage, suggesting a possible long-term trade-off.
Overall, this study expands the understanding of how telomere-related proteins influence more than just cellular aging. By identifying a connection between TRF1 and metabolism, the research opens new possibilities for targeting TRF1 or its pathways to address obesity and related conditions. Still, further studies are needed to clarify how TRF1 affects fat development and whether similar effects occur in humans.
DOI: https://doi.org/10.18632/aging.206320
Corresponding author: Maria A. Blasco — mblasco@cnio.es
Abstract video: https://www.youtube.com/watch?v=7AG3TBgDZIw
Keywords: aging, Trf1, metabolism, leaner, fat, telomeres
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
- X
- YouTube
- Bluesky
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging-US publication updates.
For media inquiries, please contact media@impactjournals.com.
Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles
Article Publication Date
17-Sep-2025
COI Statement
The authors declare that they have no conflicts of interest.