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

A 27-month study published in Molecular Therapy found that a single intramuscular injection of AAV-FGF21 gene therapy boosted life expectancy in aged mice by about 20%, according to researchers at Universitat Autònoma de Barcelona.uab
The therapy normalized body weight, improved insulin sensitivity, and preserved function across the liver, kidney, heart, and brain by turning muscle cells into steady producers of the metabolic hormone FGF21.medpath
Kriya Therapeutics, which acquired the university’s spinout in 2023, is developing a version of the therapy called KRIYA-497 for human liver disease patients.precisionmedicineonline

Single-Shot Gene Therapy Extends Mouse Lifespan by 20%, Raising Hopes for Human Aging

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

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

“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.nih

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

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