Researchers using a fast-aging fish have shown how a common diabetes drug preserves kidney health during rapid aging. The African turquoise killifish, which lives only four to six months, mimics human kidney decline, allowing quick tests of treatments. SGLT2 inhibitors maintained better kidney structures and reduced inflammation in the fish.
The African turquoise killifish offers a unique window into organ aging, completing its lifespan in just four to six months. In a study published in Kidney International, scientists from MDI Biological Laboratory, Hannover Medical School, and Colby College examined how this fish's kidneys change over time. As the fish aged, their kidneys exhibited hallmarks of human aging: loss of tiny blood vessels known as vascular rarefaction, damage to the filtration barrier, increased inflammation, and shifts in cellular energy production away from efficient mitochondria-based systems.
To test potential interventions, the team administered SGLT2 inhibitors, drugs commonly prescribed for diabetes and heart disease. Treated fish showed preserved capillary networks, stronger filtration barriers, stable energy metabolism, and reduced genetic markers of inflammation. These effects preserved communication between kidney cell types and maintained gene activity profiles similar to those in younger animals.
"These drugs are already known to protect the heart and kidneys in patients with and without diabetes," said Hermann Haller, M.D., senior author and president of MDI Biological Laboratory. "What has been less clear is how they do so."
Haller added that the findings explain clinical benefits beyond glucose control: "Together, these upstream effects provide a biological explanation for clinical observations that the benefits of SGLT2 inhibitors often exceed what would be expected from glucose control alone."
First author Anastasia Paulmann, M.D., highlighted the model's value: "Seeing these effects emerge so clearly in a rapid-aging model like our killifish was striking. What impressed me most was how a seemingly simple drug influences so many interconnected systems within the kidney—from blood vessels and energy metabolism to inflammation and overall function."
The killifish model's speed enables faster evaluation of therapies compared to mice, accelerating research on aging and organ health. Future studies will explore repair after damage and treatment timing. The work was supported by the National Institutes of Health and other foundations.
