Gene therapy prolongs health span and preserves the function of multiple organs in mice during aging

by Autonomous University of Barcelona

edited by Lisa Lock, reviewed by Robert Egan

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A research team from the Universitat Autònoma de Barcelona (UAB) has shown that a one-time administration of a gene therapy expressing the metabolic factor FGF21 can prolong health span in old mice. The 27-month pharmacology study, published in Molecular Therapy, shows sustained beneficial effects across multiple endpoints associated with aging and health span.

A study developed at the Center for Animal Biotechnology and Gene Therapy (CBATEG) of the Universitat Autònoma de Barcelona (UAB) has shown that a one-time administration of a gene therapy that induces production of the metabolic factor FGF21—fibroblast growth factor 21—by skeletal muscle can prolong health span in old and geriatric mice. The study, led by Professor Fatima Bosch and published in Molecular Therapy, shows sustained beneficial effects throughout the organism.

The research evaluated an adeno-associated viral vector (AAV) gene therapy that induces the expression and secretion of native FGF21 via administration to skeletal muscle, enabling systemic effects in aged mice. The treatment was carried out in elderly male and female mice by means of a single intramuscular injection. The results show that this intervention prolongs both life expectancy and disease-free life. In particular, the treated animals showed a 20.54% increase in life expectancy thanks to the administration of the gene therapy.

Overall improvement of metabolism and organ function

The treatment produced sustained improvements in multiple physiological functions, reducing deterioration associated with aging in different organs. The AAV-FGF21 gene therapy normalized body weight and fat accumulation, improved insulin sensitivity and glucose homeostasis, and increased energy expenditure and the functional capacity of various tissues.

The treatment showed beneficial effects in multiple organs and tissues of the treated animals. In adipose tissue, a reduction in adiposity and inflammation was observed, along with an increase in mitochondrial function. In the liver, the therapy preserved detoxification capacity and prevented alterations associated with aging, such as amyloidosis. In the kidney, markers of renal damage were reversed, and there were no signs of age-related kidney disease. In the heart, fibrosis and amyloidosis were avoided, maintaining both structure and function. In addition, physical performance was preserved, with improvements in coordination, strength and muscular endurance, while memory and learning improved to levels comparable to those of young animals.

Cellular adaptations that counteract aging

Transcriptomic and histological analyses demonstrated the benefits of the treatment through specific adaptations in each tissue that improve energy homeostasis and cellular function. These adaptations are based on coordinated molecular changes in different tissues. Specifically, improved mitochondrial function was observed, with an increase in the pathways involved in energy production. In parallel, the therapy restored proteostasis by activating protein synthesis. Finally, an increase in hepatic detoxification capacity was also detected, attributed to the regulation of key enzymes involved in these processes.

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

The work demonstrates for the first time that a gene therapy driving the expression of native FGF21 administered to old and geriatric animals not only improves metabolic parameters but also extends health span and delays age-associated multiorgan deterioration.

It should be noted that the same research group had previously demonstrated that this gene therapy based on AAV-FGF21 vectors can reverse metabolic dysfunction-associated steatohepatitis (MASH) in mouse models, a liver disease associated with obesity and diabetes. Recently, the Food and Drug Administration (FDA) allowed the clinical trial to proceed for the treatment of patients with MASH, which is scheduled to begin in 2026.

Publication details

Veronica Jimenez et al, AAV-mediated FGF21 gene therapy promotes healthspan extension by whole-body tissue-specific adaptations, Molecular Therapy (2026). DOI: 10.1016/j.ymthe.2026.05.025

Journal information: Molecular Therapy

Key medical concepts

FGF21 GeneHealthy AgingFatty Liver Disease

Clinical categories

Healthy agingFamily medicineEndocrinology Provided by Autonomous University of Barcelona Who's behind this story?

Lisa Lock

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Citation: Gene therapy prolongs health span and preserves the function of multiple organs in mice during aging (2026, June 15) retrieved 15 June 2026 from https://medicalxpress.com/news/2026-06-gene-therapy-prolongs-health-span.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.