June 15, 2026 —
Researchers at the Universitat Autònoma de Barcelona have reported preclinical data showing that a one-time administration of an AAV-FGF21 gene therapy prolonged health span in old and geriatric mice. The 27-month pharmacology study, led by Professor Fatima Bosch at the Center for Animal Biotechnology and Gene Therapy, was published in Molecular Therapy.
The therapy uses an adeno-associated viral vector, or AAV, to induce skeletal muscle expression and secretion of FGF21, a metabolic factor involved in energy balance, insulin sensitivity, lipid metabolism, and tissue function. By administering the vector through a single intramuscular injection, the researchers aimed to turn skeletal muscle into a long-term source of native FGF21, enabling systemic effects across multiple organs.
In aged male and female mice, the one-time AAV-FGF21 treatment extended life expectancy and disease-free life. Treated animals showed a 20.54% increase in life expectancy, along with sustained improvements in metabolic health, organ function, physical performance, and cognitive outcomes.
The therapy normalized body weight and fat accumulation, improved insulin sensitivity and glucose homeostasis, and increased energy expenditure. Beneficial effects were observed across multiple tissues. In adipose tissue, treatment reduced adiposity and inflammation while improving mitochondrial function. In the liver, it preserved detoxification capacity and helped prevent age-associated alterations such as amyloidosis. In the kidney, the therapy reversed markers of renal damage and prevented signs of age-related kidney disease.
Cardiac benefits were also reported, with treated animals avoiding fibrosis and amyloidosis while maintaining heart structure and function. The study also found preserved physical performance, including improvements in coordination, strength, and muscular endurance. At the brain level, treated animals showed improvements in memory and learning comparable to those observed in younger animals.
Transcriptomic and histological analyses suggested that the health-span benefits were supported by tissue-specific cellular adaptations. These included improved mitochondrial function, activation of energy-production pathways, restoration of proteostasis through protein synthesis, and increased hepatic detoxification capacity through regulation of key enzymes.
The findings suggest that AAV-mediated expression of native FGF21 may provide a long-lasting strategy to counteract age-associated metabolic and multiorgan decline in preclinical models. While the work remains preclinical, the study supports the broader potential of gene therapy approaches designed to modulate systemic aging biology through durable expression of therapeutic proteins.
The same research group previously showed that AAV-FGF21 gene therapy could reverse metabolic dysfunction-associated steatohepatitis, or MASH, in mouse models. A related clinical program for MASH, being advanced by Kriya Therapeutics, has received FDA clearance to proceed and is expected to begin clinical testing in 2026.
