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A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8\u201392 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.<\/jats:p>","DOI":"10.7554\/elife.96155","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T09:25:21Z","timestamp":1713173121000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.96155","source":"Crossref","is-referenced-by-count":12,"title":["Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4130-6204","authenticated-orcid":true,"given":"Xingfeng","family":"Shao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"USC Stevens Neuroimaging and Informatics Institute, Keck 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