Single gene therapy shot extended mouse lifespan by 20%, study finds

A single injection of gene therapy extended the lifespan of elderly mice by more than 20%, according to a study published in Molecular Therapy by researchers at the Universitat Autònoma de Barcelona. The findings mark the first demonstration that a one-time gene therapy delivering the metabolic hormone FGF21 can both extend life and delay age-related organ deterioration when administered to old animals.

A One-Shot Approach to Aging

The 27-month study, led by Professor Fatima Bosch at the university's Center for Animal Biotechnology and Gene Therapy, used an adeno-associated viral vector to deliver the FGF21 gene into skeletal muscle through a single intramuscular injection. The muscle cells then became steady producers of the FGF21 protein, releasing it into the bloodstream and generating effects across the entire body.uab+1

Treated mice showed a 20.54% increase in life expectancy compared to untreated controls. Beyond survival, the therapy normalized body weight and fat accumulation, improved insulin sensitivity and glucose metabolism, and increased energy expenditure. Organ-level analyses revealed preserved function in adipose tissue, liver, kidney, heart, and brain, while transcriptomic profiling showed improved mitochondrial function, restored proteostasis, and enhanced hepatic detoxification.news-medical+2

"These results position gene therapy based on FGF21 as a potentially translational strategy to promote healthy aging," Bosch said.uab

From Mice to Patients

The research builds on nearly a decade of work by Bosch's group, which first showed in 2018 that AAV-delivered FGF21 could reverse obesity, insulin resistance, and type 2 diabetes in mice. A subsequent study published in Molecular Therapy in late 2024 demonstrated that the same approach durably reversed liver fibrosis and halted tumor development in obese mouse models of metabolic dysfunction-associated steatohepatitis, or MASH.pubmed.ncbi.nlm.nih+3

Kriya Therapeutics, which acquired the Barcelona-based spinout Tramontane Therapeutics in 2023 to gain access to the FGF21 gene therapy platform, is developing the treatment as KRIYA-497 for MASH patients. The company, which raised $313 million in financing in 2025, lists KRIYA-497 in its clinical pipeline alongside gene therapies for geographic atrophy and type 1 diabetes.precisionmedicineonline+2

A Crowded but Promising Field

The FGF21 pathway is already being pursued through conventional drug development. 89bio has its FGF21 analog pegozafermin in Phase 3 trials for MASH. But the gene therapy approach offers a potential advantage: a single injection that produces sustained FGF21 levels without repeated dosing, a distinction Bosch's team has emphasized as particularly relevant for chronic metabolic conditions.marinbio+1