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 the turquoise coater. This small vertebrate completes its entire life in just a few months, making it a unique model for studying aging. The results shed light on the biological processes behind the kidney and heart protection these drugs provide in humans, effects that go beyond their original purpose of lowering blood sugar.
The research also positions the African turquoise robe as a valuable new tool for investigating how organs change with age and for rapidly testing treatments that could help preserve organ health later in life.
A fish that restores decades of aging in months
The African Turquoise Warbler is one of the fastest aging vertebrates known, living only four to six months. In this study, an international team of 13 scientists from MDI Biological Laboratory, Hanover Medical School, and Colby College found that fish develop kidney changes over time that closely resemble those seen in aging human kidneys.
As the fish grew, their kidneys showed loss of tiny blood vessels, damage to the filtration barrier, increased inflammation, and disruptions in the way kidney cells produce and regulate energy. These changes are well-known features of renal aging and disease in humans.
Because fish experience these processes so quickly, scientists can observe the full progression 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 angle
After establishing the hagfish as a reliable model of aging, researchers turned their attention to sodium-glucose cotransporter-2 (SGLT2) inhibitors. These drugs are commonly prescribed to treat diabetes-related heart disease and chronic kidney disease.
“These drugs are already known to protect the heart and kidneys in patients with and without diabetes,” said Hermann Haller, MD, lead author of the study and president of the MDI Biological Laboratory. “What’s less clear is how they do it.”
The study showed that fish treated with SGLT2 inhibitors maintained healthier kidneys as they aged. Their kidneys retained denser networks of capillaries, stronger filtration barriers and more stable energy production in cells.
The treatment also helped preserve communication between different types of kidney cells and reduce age-related inflammatory activity at the genetic level.
“Together, these upstream effects provide a biological explanation for the clinical observations that the benefits of SGLT2 inhibitors often exceed what would be expected from glucose control alone,” Haller said. “They help explain why these drugs consistently reduce kidney and cardiovascular events in different patient populations.”
Preservation of blood vessels and cellular energy
In untreated fish, one of the most striking signs of kidney decline was the gradual loss of capillaries, a process known as vascular rarefaction. As these tiny blood vessels disappeared, kidney cells shifted away from efficient mitochondrial-based energy production and relied more on less efficient backup systems.
Fish that received SGLT2 inhibitors showed a very different pattern. Their kidneys retained healthier capillary networks and showed gene activity that more closely matched that of younger animals. These so-called “youthful transcriptional profiles” were associated with better energy metabolism and lower levels of inflammation.
Accelerating aging research with human relevance
The study’s first author, Anastasia Paulmann, MD, previously worked as a postdoctoral researcher at the MDI Bio Lab and also holds a clinical position at Hannover Medical School. She established and maintained a colony of coatis in the laboratory of the Kathryn W. Davis Center for Regenerative Biology and Aging. According to Paulmann, this model offers a powerful way to accelerate aging research while keeping it closely connected to human health.
“Seeing these effects show up so clearly in a model of rapid aging like our gown,” Paulmann said. “What impressed me most was how a seemingly simple drug affects so many interconnected systems in the kidney—from blood vessels and energy metabolism to inflammation and overall function.”
By condensing decades of kidney aging into just a few months, the model provides a practical way to assess how existing and experimental treatments affect organ resilience over time. This approach can help researchers identify the most promising therapies before moving them into human clinical trials.
The team plans follow-up studies to see if SGLT2 inhibitors can help repair kidney tissue after age-related damage has already occurred. They also aim to examine how the timing and duration of treatment shape long-term outcomes.
This future work will be supported by expanded and renovated laboratory facilities in the MDI Bio Lab as part of the institution’s MDI Bioscience initiative, which focuses on translating basic science discoveries into strategies to improve human health.
This research was supported by the National Institutes of Health (P30GM154610, P20GM203423), the Morris Discovery Fund, the Scott R. McKenzie Foundation, and the MDI Biological Laboratory.
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