Juntendo University researchers find that podocytes in aged rats undergo structural remodeling to maintain renal function
Podocytes are specialized cells in the kidneys that do not renew with age. Researchers from Juntendo University used electron microscopy to show that podocytes in older rats are much larger and have significant structural differences from those in young rats. These findings highlight age-related structural changes and could increase the accuracy of staging the progression of glomerular disorders in kidneys.
The kidneys are vital organs that sustain life by filtering the blood and producing urine. This filtration process takes place in specialized structures called glomeruli, where podocytes play a crucial role by forming the filtration barrier on the glomerular surface. Mature podocytes cannot regenerate once lost, which means that the podocytes generated during fetal development must be used throughout life. It is well known that the number of podocytes decreases with age; however, lost podocytes are not replaced by newly generated cells, and continued podocyte depletion ultimately leads to loss of glomerular function. Therefore, the remaining podocytes are thought to adapt in order to preserve glomerular function despite a reduction in cell number; however, how podocytes adapt to this loss has long remained unclear. In this study, the research team employed array tomography (AT), a technique that enables whole-cell observation of podocytes with their complex three-dimensional architecture, to elucidate age-related structural changes in podocytes in rats. Their findings were made available online on December 17, 2025, in the
Journal of the American Society of Nephrology.
AT is an advanced imaging technique in which thousands of serial tissue sections are imaged using scanning electron microscopy, enabling high-resolution, three-dimensional observation of relatively large tissue volumes. The research team optimized the standard AT workflow to enable analysis of entire glomeruli, thereby establishing a technique that allows visualization of the complete structure of any individual podocyte within a glomerulus.
In this study, whole-cell three-dimensional reconstructions of podocytes were generated from rats at young (1.5 months of age), adult (6 months of age), and aged (24 months of age) stages. The reconstructed podocytes could be examined on a PC from any desired orientation, and quantitative evaluations, including measurements of cell volume, could be performed.
In the present study, eight distinct types of structural changes associated with podocyte aging were identified. It is known that podocytes are gradually lost with age, resulting in a reduction in cell number; however, this study further demonstrated that portions of podocytes undergo fragmentation and are subsequently lost.
As podocytes are lost, podocyte density on the glomerular surface decreases, while the volume of remaining aged podocytes increases markedly. The volume of aged podocytes was found to be approximately 4.6-fold greater, indicating compensatory hypertrophy in response to podocyte loss. In addition, areas lost through fragmentation were repaired by coverage from surrounding podocytes, during which atypical self-cellular junctions were frequently formed. These autocellular junctions are entirely absent in normal glomeruli and are considered to represent structural “footprints” of injury repair in aging glomeruli.
Furthermore, although aging cells generally exhibit a decline in intracellular degradation capacity for unnecessary cellular components, podocytes were found to compensate for this functional decline by exporting such materials into the extracellular space rather than degrading them intracellularly.
The research team is currently analyzing human podocytes, and preliminary findings indicate that aging-related structural changes in human podocytes are more diverse than those observed in rats. The longer lifespan of humans compared with that of rats is expected to be a key factor in elucidating these structural changes. To characterize the aging process of human podocytes, analyses across a wide age range are required, and additional factors such as sex and the presence of underlying diseases must also be taken into consideration.
The research team has already begun comprehensive analyses of human podocyte aging by utilizing kidney biopsy specimens obtained at the affiliated university hospital. Furthermore, because AT enables observation of entire glomeruli, the team plans to apply this technique in the future to glomerular pathology specimens to analyze low-density or focal lesions that are often overlooked by conventional pathological methods.
About Dr. Takashi Amari
Takashi Amari is a Research Fellow at the Department of Anatomy and Life Structure, Juntendo University Graduate School of Medicine, Japan. Dr. Amari received his doctorate in 2024. His work focuses on physical therapy, rehabilitation science, and renal function.
About Dr. Takayuki Miyaki
Takayuki Miyaki is an Assistant Professor at the Department of Anatomy and Life Structure, Juntendo University Graduate School of Medicine, Japan. Dr. Miyaki’s research focuses on cell biology and anatomy, with an emphasis on studying renal structure through electron microscopy.
Original Source
https://en.juntendo.ac.jp/highlights/news/nid1263
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Juntendo was originally founded in 1838 as a Dutch School of Medicine at a time when Western medical education was not yet embedded as a normal part of Japanese society. With the creation of Juntendo, the founders hoped to create a place where people could come together with the shared goal of helping society through the powers of medical education and practices. Their aspirations led to the establishment of Juntendo Hospital, the first private hospital in Japan. Through the years the institution's experience and perspective as an institution of higher education and a place of clinical practice has enabled Juntendo University to play an integral role in the shaping of Japanese medical education and practices. Along the way the focus of the institution has also expanded, now consisting of nine undergraduate programs and six graduate programs, the university specializes in the fields of health science, health and sports science, nursing health care and sciences, and international liberal arts, as well as medicine. Today, Juntendo University continues to pursue innovative approaches to international level education and research with the goal of applying the results to society.
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