TRF1 protein loss reduces physique fats and improves metabolic well being in mice with out shortening telomeres

“These findings uncover a previously unknown role of TRF1 in regulating metabolism.”

BUFFALO, NY — October 27, 2025 — A brand new analysis paper was printed 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 examine led by first writer Jessica Louzame Ruano and corresponding writer Maria A. Blasco from the Spanish National Cancer Centre (CNIO), researchers investigated the position of TRF1, a protein identified for shielding telomeres, in regulating whole-body metabolism. The outcomes counsel that TRF1 influences metabolic well being by way of mechanisms unrelated to its identified operate in telomere upkeep.

Obesity and metabolic issues are main well being considerations, particularly as individuals age. To discover TRF1’s position past telomere safety, the analysis crew studied each regular mice and genetically modified mice that lacked TRF1. Mice with out TRF1 remained leaner over time, resisted fats accumulation, and confirmed more healthy blood sugar and insulin ranges in comparison with regular mice. Importantly, these advantages occurred with none detectable shortening of telomeres.

The leaner physique composition in TRF1-deficient mice was not resulting from diminished meals consumption or elevated bodily exercise. Instead, the fats loss appeared to consequence from organic adjustments in how power was processed and saved. Male mice with out TRF1 gained much less weight and had decrease LDL levels of cholesterol, even on a high-fat weight loss plan. Female mice confirmed milder results, reflecting identified sex-based variations in susceptibility to diet-induced weight problems. This highlights the significance of together with each sexes in metabolic analysis.

“Major metabolic pathways related with energy production and regulation of metabolism homeostasis were also found downregulated in Trf1-deficient mice.”

Gene expression evaluation within the liver revealed shifts in a number of key pathways. Genes associated to fats manufacturing, power era, and muscle progress have been downregulated, whereas genes linked to irritation and ldl cholesterol synthesis have been upregulated. The mice additionally confirmed indicators of upper power expenditure and a shift from utilizing fats to protein as an power supply, probably resulting from their diminished fats reserves. However, some older mice developed delicate liver stress, together with fibrosis and DNA injury, suggesting a doable long-term trade-off.

Overall, this examine expands the understanding of how telomere-related proteins affect extra than simply mobile growing older. By figuring out a connection between TRF1 and metabolism, the analysis opens new prospects for concentrating on TRF1 or its pathways to deal with weight problems and associated circumstances. Still, additional research are wanted to make clear how TRF1 impacts fats growth and whether or not related results happen in people.

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

Corresponding writer: Maria A. Blasco — mblasco@cnio.es

Abstract video: https://www.youtube.com/watch?v=7AG3TBgDZIw

Keywords: growing older, Trf1, metabolism, leaner, fats, telomeres

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