A Fish that Ages Within Months Shows How Kidneys Age

A new study published in Kidney International reports that a class of drugs called SGLT2 inhibitors helped prevent age-related damage to kidney structure and function in African turquoise killifish. This small vertebrate completes its entire life cycle in just a few months, making it a unique model for studying aging.

The findings shed light on the biological processes behind the protection of the kidneys and heart by these drugs in humans—effects that go beyond their original purpose of lowering blood sugar levels. The research also positions the African turquoise killifish as a valuable new tool for studying how organs change with age and for rapidly testing treatments that could help maintain organ health in later life.

A Fish that Goes Through Decades of Aging in Just a Few months

The African turquoise killifish (Nothobranchius furzeri) is a small freshwater fish from southeastern Africa, found mainly in Mozambique and Zimbabwe. It is one of the fastest-aging vertebrates known, living only four to six months. It is characterized by its striking appearance: the males have an intense turquoise-blue coloration with red markings on their fins and body, while the females are much more inconspicuous and tend to be brownish-gray in color. Adult animals reach a length of about five to six centimeters. They have a compact build and relatively large, rounded fins. In this study, an international team of 13 scientists from the MDI Biological Laboratory, Hannover Medical School, and Colby College found that over time, the fish develop changes in their kidneys that are very similar to those seen in aging human kidneys.

As the fish aged, their kidneys showed a loss of small blood vessels, damage to the filtration barrier, increasing inflammation, and disturbances in energy production and regulation in the kidney cells. These changes are known characteristics of kidney aging and disease in humans. Because these processes occur so rapidly in fish, researchers can observe the entire course of kidney aging in a short period of time. This allows potential therapies to be tested much more quickly than in longer-lived animals such as mice.

A Widely Used Drug Examined from a New Perspective

Once killifish were established as a reliable model of aging, the researchers turned their attention to sodium-glucose cotransporter 2 (SGLT2) inhibitors. These drugs are often prescribed to treat diabetes-related heart disease and chronic kidney disease.

“It is already known that these drugs protect the hearts and kidneys of patients with and without diabetes,” said Dr. Hermann Haller, lead author of the study and president of the MDI Biological Laboratory. “What was less clear until now was how they do that.”

The study showed that fish treated with SGLT2 inhibitors maintained healthier kidneys as they aged. Their kidneys retained a denser capillary network, stronger filtration barriers, and more stable energy production in the cells. The treatment also helped maintain communication between different types of kidney cells and reduced age-related inflammatory activity at the genetic level.

“Together, these upstream effects provide a biological explanation for clinical observations that the benefits of SGLT2 inhibitors often go beyond what would be expected from glucose control alone,” Haller said. “They help explain why these drugs consistently reduce kidney and cardiovascular events in various patient groups.”

Preserving Blood Vessels and Cellular Energy in the Kidneys

In untreated fish, one of the most striking signs of kidney dysfunction was the gradual loss of capillaries, a process known as vascular impoverishment. As these small blood vessels disappeared, kidney cells ceased their efficient, mitochondria-based energy production and relied more heavily on less effective substitute systems.

Fish given SGLT2 inhibitors showed a very different pattern. Their kidneys retained a healthier capillary network and exhibited gene activity more consistent with younger animals. These so-called “youthful transcription profiles” were associated with better energy metabolism and lower inflammation levels.

Accelerating aging research with relevance for humans

The study’s first author, Dr. Anastasia Paulmann, previously worked as a postdoctoral fellow at the MDI Bio Lab and also holds a clinical position at Hannover Medical School. She founded and maintained the killifish colony at the lab’s Kathryn W. Davis Center for Regenerative Biology and Aging. According to Paulmann, the model offers a powerful way to accelerate aging research while maintaining a close connection to human health.

“It was impressive to see these effects so clearly in a model of rapid aging like our killifish,” Paulmann said. “What impressed me most was how a seemingly simple drug affects so many interconnected systems within the kidney—from blood vessels and energy metabolism to inflammation and overall function.”

By condensing decades of kidney aging into a few months, the model offers a practical way to evaluate how existing and experimental treatments affect organ resilience over time. This approach can help researchers identify the most promising therapies before they move on to human clinical trials.

The team plans to conduct follow-up studies to determine whether SGLT2 inhibitors can help repair kidney tissue after age-related damage has already occurred. They also want to investigate how the timing and duration of treatment affect long-term outcomes. This future work will be supported by expanded and renovated laboratory facilities at the MDI Bio Lab, part of the institution’s MDI Bioscience Initiative, which focuses on translating fundamental scientific discoveries into strategies for improving human health.