BARCELONA — A research team led by Professor Fatima Bosch at the Universitat Autònoma de Barcelona demonstrated that a single-dose gene therapy extended both the life span and health span in aged mice. The findings, published in the journal Molecular Therapy, resulted from a 27-month pharmacology study.

The gene therapy expresses native fibroblast growth factor 21 and was administered as a single intramuscular injection to elderly male and female mice. The treatment utilizes an adeno-associated viral vector to induce skeletal muscle to produce the native fibroblast growth factor 21.

The treated animals showed a 20.54 percent increase in life expectancy. The therapy also normalized body weight and fat accumulation in the treated mice. Additionally, the treatment improved insulin sensitivity and glucose homeostasis.

Analysis of the treated animals' tissues indicated several improvements. In the adipose tissue, the intervention reduced inflammation and increased mitochondrial function. The therapy preserved detoxification capacity and prevented amyloidosis in the liver, while in the kidney, it reversed markers of renal damage and showed no signs of age-related disease. In the heart, the treatment prevented fibrosis and amyloidosis, maintaining tissue structure and function.

Treated mice maintained physical coordination, strength, and muscular endurance comparable to younger animals. Transcriptomic and histological analyses indicated the therapy restored proteostasis by activating protein synthesis. This work marks the first demonstration that a gene therapy expressing native FGF21 extends health span in aged mice. Bosch said, "These results position gene therapy based on FGF21 as a potentially translational strategy to promote healthy aging."