As the body ages, bones undergo changes that can hinder their ability to regenerate and heal. While previous studies have concentrated on the structural shifts in bone tissue itself, the role of nerves and blood vessels—critical players in bone health—has remained relatively unexplored. 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.
Researchers from Johns Hopkins University have published new findings (DOI: 10.1038/s41413-025-00401-8) in Bone Research (February 2025), 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 plays 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.
“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.
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References
DOI
10.1038/s41413-025-00401-8
Original Source URL
https://doi.org/10.1038/s41413-025-00401-8
Funding information
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).
About Bone Research
Bone Research was founded in 2013. As a new English-language periodical, Bone Research focuses on basic and clinical aspects of bone biology, pathophysiology and regeneration, and supports the foremost discoveries resulting from basic investigations and clinical research related to bone. The aim of the Journal is to foster the worldwide dissemination of research in bone-related physiology, pathology, diseases and treatment.