A team of researchers at the Autonomous University of Barcelona (UAB) has shown that a single dose of gene therapy that expresses the metabolic factor FGF21 can extend the healthy lifespan of old mice. A 27-month pharmacology study published in the journal Molecular Therapy showed sustained beneficial effects across multiple endpoints related to aging and healthspan.
A study conducted at the Center for Animal Biotechnology and Gene Therapy (CBATEG) at the Autonomous University of Barcelona (UAB) shows that a single dose of gene therapy that induces skeletal muscle production of the metabolic factor FGF21 (fibroblast growth factor 21) can extend the healthy lifespan of old mice. The study, led by Professor Fatima Bosch and published in Molecular Therapy, the leading scientific journal in the field of gene therapy, shows lasting beneficial effects throughout the organism.
In this study, we evaluated an adeno-associated viral vector (AAV) gene therapy that induces native FGF21 expression and secretion upon administration to skeletal muscle, enabling systemic effects in aged mice. The treatment was administered by a single intramuscular injection to older male and female mice. Results show that this intervention increases both life expectancy and disease-free life. Specifically, the administration of gene therapy increased the life expectancy of treated animals by 20.54%.
Overall improvement in metabolism and organ function
This treatment reduced age-related functional decline in various organs and produced sustained improvements in multiple physiological functions. AAV-FGF21 gene therapy normalized body weight and fat accumulation, improved insulin sensitivity and glucose homeostasis, and increased energy expenditure and functional capacity of various tissues.
The treatment showed beneficial effects on multiple organs and tissues in treated animals. In adipose tissue, a decrease in fat accumulation and inflammation was observed along with an increase in mitochondrial function. In the liver, this treatment maintained its detoxification capacity and prevented age-related changes such as amyloidosis. In the kidneys, there was evidence of recovery of kidney damage markers and absence of signs of age-related kidney disease. In the heart, fibrosis and amyloidosis were avoided, and both its structure and function were preserved. Furthermore, physical performance was maintained, coordination, muscle strength, and muscular endurance improved, and at the brain level, significant improvements in memory and learning comparable to those in young animals were detected.
Cellular adaptations to combat aging
Transcriptomic and histological analyzes demonstrated the benefits of treatment with specific adaptations for each tissue to improve energy homeostasis and cellular function. These adaptations are based on coordinated molecular changes in different tissues. Specifically, improvements in mitochondrial function were observed, along with an increase in pathways involved in energy production. In parallel, this treatment restored proteostasis by activating protein synthesis. Finally, an increase in the detoxification capacity of the liver was also detected, which can be attributed to the regulation of key enzymes involved in these processes.
Lead researcher Fatima Bosch said:These results position FGF21-based gene therapy as a potential translational strategy to promote healthy aging.. ”
This study demonstrates for the first time that administering a gene therapy that promotes native FGF21 expression to old animals not only improves metabolic parameters, but also extends healthy lifespan and slows age-related deterioration of multiple organs.
It should be noted that the same research group has previously demonstrated that this gene therapy based on the AAV-FGF21 vector can reverse metabolic dysfunction-associated steatohepatitis (MASH), a liver disease associated with obesity and diabetes, in a mouse model (Jimenez, V et al. Mol. Ther. 2024; 32:4285-4302). Recently, the FDA allowed clinical trials to proceed for the treatment of MASH patients. The clinical trial will be conducted by biopharmaceutical company Kriya Therapeutics (https://kriyatherapeutics.com/) and is expected to begin in 2026.
sauce:
Autonomous University of Barcelona (UAB)
Reference magazines:
Jimenez, V. Others. (2026). AAV-mediated FGF21 gene therapy promotes healthy lifespan extension through systemic tissue-specific adaptation. molecular therapy. DOI: 10.1016/j.ymthe.2026.05.025. https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(26)00469-7
