Abstract: SA-PO0009
Vitamin D Receptor Deficiency Accelerates Organ-Specific Trajectories of Premature Aging in Mice: Kidneys as the Earliest Target
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Chen, Xujiao, Huashan Hospital Fudan University, Shanghai, China
- You, Huaizhou, Huashan Hospital Fudan University, Shanghai, China
- Chen, Jing, Huashan Hospital Fudan University, Shanghai, China
Background
Aging is a complex process influenced by a variety of factors and demonstrates organ-specific characteristics, but the mechanisms are still not well understood. Vitamin D acts through the vitamin D receptor (VDR), which exhibits strong spatiotemporal specificity. Deficiency in vitamin D/VDR system is a global health issue linked to numerous age-related diseases. However, how VDR regulates organ-specific aging and the underlying mechanisms remain unclear.
Methods
To explore the relationship between VDR and aging, we established a VDR knockout (KO) mouse model. Single cells RNA sequencing (scRNA-seq) on kidneys from VDR KO and control mice was performed to determine the specific alterations and underlying mechanisms of VDR deficiency in regulating the aging process. Micro-CT imaging following Microfil perfusion was applied to visualize renal microvasculature. We further established renal PDGFRβ+ pericyte-specific VDR knockdown and overexpression mouse models using adeno-associated virus serotype 9.
Results
In this study, we demonstrated that VDR KO leads to premature aging in organ-specific patterns, with the kidneys emerging as the earliest and most severely affected organ. Single-cell RNA sequencing revealed that pericytes were the most affected kidney cell type, showing pronounced loss, and transdifferentiation into myofibroblasts. Further angiography, immunofluorescence, and histopathology analysis revealed a loss of pericytes, reduced microvascular density, and increased myofibroblast accumulation in the kidney of VDR knockout mice. The kidney pericyte-specific VDR knockdown mouse model exhibited significant pericyte loss, microvascular rarefaction, and myofibroblast accumulation, which leading to renal aging phenotypes, whereas VDR overexpression alleviated these alterations. Using primary cell culture and a 3D angiogenesis model, we confirmed in vitro that VDR knockdown enhanced, while VDR activation suppressed pericyte-myofibroblast transdifferentiation, and impaired angiogenic function.
Conclusion
These findings identify VDR as a crucial factor in governing the organ-specific aging, highlighting the kidney's early vulnerability to VDR loss, and suggest that targeting pericytes VDR signaling may protect vitamin D deficiency-related aging.