Researchers have created the first 3D visualizations of how nerves and blood vessels in the skull change with age, showing a decline in neurovascular density over time.
New research sheds light on how the neurovascular structure of the murine calvarium, the upper part of the skull, evolves with age. Using advanced 3D imaging techniques, scientists identified significant age-related changes in the distribution and density of nerves and blood vessels within the skull.
These findings provide valuable insights into the effects of aging on skeletal structure and may help explain age-related bone fragility and reduced regenerative capacity. The study underscores the critical role of neurovascular interactions in bone health, laying the groundwork for future research on bone regeneration and repair.
As the body ages, bones lose some of their ability to heal and regenerate. While previous studies have focused on structural changes in bone tissue, the influence of nerves and blood vessels—key components in bone maintenance—has remained largely unexplored. This research highlights their potential role in age-related skeletal decline.
Nerves help maintain bone homeostasis and are key to responding to injury, but how they interact with blood vessels in the skull throughout aging was unknown until now. Given the difficulty of imaging three-dimensional (3D) structures within bones, comprehensive data on these age-related changes have been scarce. This research fills that gap, providing the first detailed look at how neurovascular interactions evolve in the skull.
Breakthrough 3D Visualizations of Aging Neurovascular Structures
Researchers from Johns Hopkins University have published new findings the journal in Bone Research, offering the first-ever 3D visualizations of how nerves and blood vessels in the murine calvarium change with age. Using cutting-edge lightsheet microscopy, the team traced the neurovascular architecture from birth to 80 weeks of age. Their results provide groundbreaking insights into the aging process of skull bones, showing how nerves and blood vessels interact and decline over time.
This study provides the most detailed analysis to date of age-related changes in the calvarial neurovascular architecture. The team used 3D lightsheet microscopy to capture high-resolution images of nerves and blood vessels at various stages of life, from post-natal day zero to 80 weeks of age. They observed a steady increase in nerve density in the first few weeks of life, followed by a significant decline in older mice, particularly in the frontal bone. In addition to these changes in nerve density, the study also noted that blood vessels in the calvarium exhibited distinct patterns of aging.
The association between nerves and blood vessels, which play a crucial role in bone development and regeneration, also weakened as the animals aged. Importantly, these changes occurred at different rates depending on the region of the skull, with the frontal bone showing earlier signs of neurovascular decline. These findings underscore the complexity of bone aging and provide crucial data for further studies on bone fragility and regenerative medicine.
Implications for Bone Health and Future Therapies
“This research opens up new avenues for understanding how nerves and blood vessels influence bone aging and regeneration,” said Dr. Warren Grayson, one of the lead researchers. “The ability to visualize and quantify these changes in 3D is a significant step forward in our understanding of skeletal health. These insights could help guide future therapeutic strategies for age-related bone diseases and injury recovery.”
The findings of this study have profound implications for treating age-related bone diseases such as osteoporosis and improving recovery from bone injuries. By mapping the changes in neurovascular architecture, researchers can better understand the mechanisms behind bone fragility and impaired healing in older individuals. Moreover, these insights could pave the way for therapies that target neurovascular signaling to enhance bone regeneration and improve the effectiveness of treatments for bone injuries and diseases.
Reference: “3D imaging reveals changes in the neurovascular architecture of the murine calvarium with aging” by Allison L. Horenberg, Yunke Ren, Eric Z. Zeng, Alexandra N. Rindone, Arvind P. Pathak and Warren L. Grayson, 21 February 2025, Bone Research.
DOI: 10.1038/s41413-025-00401-8
This work was supported by funding from NIDCR (1R01DE027957), Maryland Stem Cell Research Fund (2022-MSCRFV-5782), the NSF GRFP and NCI (5R01CA237597-05, 2R01CA196701-06A1).
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