New research published in *kidney International* suggests common diabetes and heart medications, known as SGLT2 inhibitors, may offer a novel approach to preventing age-related kidney decline. The study, utilizing the rapidly aging African turquoise killifish, revealed a biological mechanism explaining the drugs’ protective effects beyond blood sugar control – a finding with notable implications given the rising prevalence of chronic kidney disease affecting an estimated 37 million adults in the United States. [[1]] Scientists are hopeful the findings will accelerate the development of therapies to combat this often-silent condition.
A class of drugs known as SGLT2 inhibitors may prevent age-related decline in kidney structure and function, according to a new study published in the journal Kidney International. The findings, obtained through experiments on a rare African fish that ages rapidly, offer a deeper understanding of how these medications protect not only blood sugar levels but also the heart and kidneys.
The research provides a biological explanation for the protective effects of SGLT2 inhibitors observed in humans, extending beyond their well-established role in managing diabetes. Understanding these mechanisms is crucial as kidney disease affects millions worldwide and often goes undetected in its early stages.
Researchers focused on the African turquoise killifish, one of the fastest-aging vertebrates, completing its entire life cycle in just four to six months. This accelerated aging process makes it an ideal model for studying the effects of age-related decline.
An international team of 13 scientists from MDI Biological Laboratory, the University of Hanover Medical School, and Colby College found that the kidneys of these fish undergo changes with age that closely mirror those seen in human kidneys. These changes include the loss of tiny blood vessels, damage to the kidney’s filtration barrier, increased inflammation, and disruptions in cellular energy production – all hallmarks of kidney aging and chronic disease.
A Fast-Track Research Model
The killifish’s rapid aging allows researchers to observe the complete aging process of organs and test treatments much faster than with longer-lived animal models like mice, which can take years to show similar results. This accelerated timeline is a significant advantage in accelerating medical discoveries.
A Familiar Drug with Unexpected Effects
Building on this accelerated aging model, the team investigated the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors, drugs widely used to treat diabetes, heart disease, and chronic kidney disease.
“These drugs are known to protect the heart and kidneys in patients with and without diabetes, but what hasn’t been clear is the precise biological mechanism behind that,” said Dr. Hermann Haller, lead researcher and chief scientist at MDI Biological Laboratory.
Striking Results: Younger-Looking Kidneys
The study revealed that fish treated with SGLT2 inhibitors maintained a denser network of capillaries, preserved the integrity of the kidney’s filtration barrier, and showed improved stability in cellular energy production. The treatment also helped maintain communication between different types of kidney cells and reduced genetic signals associated with age-related inflammation.
“These early effects explain why the benefits of these drugs go beyond what we would expect from sugar control alone, and why they consistently reduce the risk of kidney and heart disease across different patient populations,” Haller added.
Protecting the Kidney’s Most Vulnerable Structures
One of the most prominent features of age-related kidney decline is the loss of capillaries, a condition known as vascular rarefaction. In untreated fish, these vessels faded, cells shifted to less efficient energy pathways, and cellular inflammation increased.
However, in fish treated with SGLT2 inhibitors, the kidneys retained healthy vascular networks and exhibited gene expression patterns resembling those found in younger organisms. This “youthful” genetic profile was linked to improved energy metabolism and reduced inflammation.
From Rapid Discovery to Human Health
“It was striking to see these effects emerge so clearly in a fast-aging model like the killifish,” said Dr. Anastasia Polman, first author of the study and a physician at Hanover Medical School. “What really amazed me was how a single drug impacts interconnected networks within the kidney, from blood vessels to energy and inflammation.”
She added that this model accelerates aging research, allows for rapid testing of existing and new treatments, and helps prioritize the most promising drugs for clinical trials in humans.
Future Research
The team plans to conduct further studies to determine whether SGLT2 inhibitors can repair kidney tissue after damage has occurred and how the timing and duration of treatment affect long-term outcomes. This work will support the expansion and modernization of MDI Biological Laboratory’s facilities as part of the MDI Bioscience initiative, which aims to translate basic discoveries into practical solutions that improve human health.
