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A new study published in Kidney International reveals that a class of drugs called SGLT2 inhibitors may prevent the deterioration of kidney structure and function as people age. The groundbreaking research, conducted using a rapidly aging African fish, offers a precise biological clarification for how these drugs protect not only the kidneys but also the heart, extending benefits beyond their established role in managing blood sugar.
The findings represent a significant step forward in understanding the mechanisms behind these increasingly popular medications and could pave the way for broader preventative applications.
The Fast-Aging Killifish: A Novel Research Model
Researchers turned to the african turquoise killifish, a unique vertebrate that lives only a few months, experiencing age-related physiological changes in a compressed timeframe. This allows scientists to study the aging process and test potential interventions much faster than with customary animal models.
as the killifish age, they exhibit changes mirroring those seen in human kidneys:
- Increased inflammation
- Disturbance of energy production within cells
These changes are all well-known hallmarks of aging kidneys and associated chronic diseases.
unveiling the Mechanism of SGLT2 Inhibitors
The international team of 13 scientists, representing institutions including MDI Biological Laboratory, Hannover Medical school, and Colby College, investigated the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors – drugs already widely used in the treatment of diabetes, heart disease, and chronic kidney disease.
“These drugs are known to protect the heart and kidneys in diabetics and non-diabetics,but what has not been clear is the exact biological mechanism behind this,” explained a senior investigator involved in the study.
The results were remarkable. Fish treated with SGLT2 inhibitors demonstrated:
- Retention of denser networks of capillaries
- Maintenance of the integrity of the renal filtration barrier
- Improved stability in cellular energy production
Furthermore, the treatment helped maintain communication between different types of renal cells and reduced genetic signals associated with age-related inflammation.
protecting the Kidney’s Most Vulnerable Systems
A key finding centered on vascular atrophy,the loss of capillaries,a prominent feature of age-related kidney decline. In untreated fish, these vessels vanished, cells shifted to less efficient energy pathways, and cellular inflammation increased. However, fish treated with SGLT2 inhibitors maintained healthy vascular networks and exhibited gene expression patterns resembling those found in younger organisms. These “youthful genetic profiles” correlated with improved energy metabolism and decreased inflammation.
“These early effects explain why the benefits of these drugs go beyond what we would expect from glucose control alone, and why they consistently reduce the risks of kidney and heart disease in different categories of patients,” the senior investigator added.
From Rapid Detection to Human Health
According to a physician at Hannover Medical School and the study’s first author, “It was remarkable to see these effects so clearly demonstrated in a rapidly aging model like the killifish. What really amazed me was how a single drug affects interconnected networks within the kidney, from blood vessels to energy and inflammation.”
the killifish model,she explained,accelerates aging research,allows for rapid testing of existing and new treatments,and helps prioritize the most promising drugs for human clinical trials.
Future Research and expanding the Scope of Finding
The research team plans to investigate whether SGLT2 inhibitors can repair kidney tissue after damage has occurred and how the timing and duration of treatment impact long-term outcomes. This work will also support the expansion and modernization of MDI laboratory facilities as part of the MDI Bioscience Initiative, aiming to translate basic discoveries into practical solutions for improving human health.
