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Indeed, the concept of a \u201cbone-vascular axis\u201d has long been recognized, supported by epidemiological evidence linking osteoporosis and low bone mass to increased cardiovascular morbidity and mortality. Emerging findings now extend this paradigm to the brain, suggesting that bone- and bone marrow\u2013derived signals influence cerebrovascular structure, function, and aging. Given that cerebrovascular dysfunction is a central driver of age-related cognitive decline, dementia, and neurodegenerative diseases, understanding this \u201cbone-cerebrovascular axis\u201d may offer novel opportunities for prevention and intervention. Here, we outline the cellular and molecular mechanisms underlying age-associated neurovascular impairment and summarize the biology of major bone and bone marrow cell populations, with emphasis on age-related alterations in their secretome. A central focus of this Review is the emerging evidence that age-related skeletal alterations exert systemic effects on the cerebrovasculature, highlighting how bone- and bone marrow\u2013derived factors shape neurovascular health and pathology, which may subsequently contribute to CNS aging and neurodegeneration. A deeper understanding of these systemic interactions reframes brain aging within a whole-body context and may uncover innovative biomarkers and therapeutic strategies to mitigate neurodegeneration and other age-associated disorders.<\/jats:p>","DOI":"10.1172\/jci207273","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:01:13Z","timestamp":1784052073000},"source":"Crossref","is-referenced-by-count":0,"title":["The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-9552","authenticated-orcid":true,"given":"Jiekang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery and"},{"name":"Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 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