Gene therapy extends healthy aging in mice

The therapy had a comprehensive positive effect on metabolism and organ function. In the adipose tissue, inflammation and fat deposits decreased, and mitochondrial function improved. In the liver, detoxification capacity was preserved, and age-related changes, including amyloidosis, were prevented. In the kidneys, markers of damage were normalized, and signs of age-related disease were not observed. In the heart, fibrosis and amyloidosis were avoided, preserving the organ’s structure and function.

In addition, the mice showed improved physical performance, including improved coordination, strength, and muscle endurance. Their cognitive abilities, memory, and learning capacity also improved, reaching the levels of young animals.

At the molecular level, the therapy induced several adaptations that counteract aging. Transcriptomic and histological analyses revealed the following changes:

• improved mitochondrial function and enhanced energy production pathways;
• restoration of proteostasis (maintenance of protein balance) by activating protein synthesis
• increased liver detoxification capacity due to regulation of key enzymes.

The results obtained allow us to consider FGF21-based gene therapy as a potentially applicable strategy for stimulating healthy aging. For the first time, it has been shown that such therapy in elderly animals not only improves metabolic parameters, but also slows down the age-related deterioration of several organ functions.

Earlier, the same research team proved that gene therapy using AAV‑FGF21 can reverse metabolic dysfunction-related steatohepatitis (MASH – a liver disease associated with obesity and diabetes). Based on these data, the US Food and Drug Administration (FDA) has authorized clinical trials for the treatment of patients with MASH. Their start is scheduled for 2026.