{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:15:08Z","timestamp":1792167308704,"version":"4.4.0"},"reference-count":77,"publisher":"National Academy of Sciences","issue":"18","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:p>\n                    The focus of this study is to investigate the role of diffusion tensor imaging along the perivascular space (DTI-ALPS) index in brain aging. To address this, we first examined the association of DTI-ALPS with aging hallmarks among 40,488 UK Biobank (UKB) participants. Next, we developed normative brain age models incorporating the DTI-ALPS index from 12,401 healthy UKB adults and validated in UKB-ADNI and UKB-TALENT datasets. Finally, we explored the relationship between brain age gap (BAG) with peripheral organ function, chronic diseases, proteomics, and genetics, while identifying modifiable factors in a longitudinal cohort. The findings revealed that DTI-ALPS index correlated with chronological age, telomere length, brain structure, and cognition. A brain age model integrating the DTI-ALPS index achieved good accuracy in the UKB (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    = 0.756) and replicated well in two independent datasets (UKB-ADNI:\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    = 0.766; UKB-TALENT:\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    = 0.724), with choroid plexus volume emerging as an additional contributor. Musculoskeletal health was a key driver for brain aging in females, while pulmonary metrics prevailed in males. Neurodegenerative and metabolic disorders increased BAGs, imparting increased mortality risk. Protein-wide and genome-wide analysis identified 154 BAG-related proteins and 11 loci. Modifiable factors, particularly systolic blood pressure below 120 mmHg, were strongly associated with reduced BAGs. Overall, the DTI-ALPS index is a promising brain aging biomarker, offering insights into links between brain and peripheral health, and highlighting sex-stratified therapeutic strategies. Aggressive blood pressure control may mitigate brain aging and promote long-term brain health.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2516601123","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:05:09Z","timestamp":1777316709000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling the glymphatic system\u2019s role in brain aging: A comprehensive biomarker and modifiable intervention target"],"prefix":"10.1073","volume":"123","author":[{"given":"Yuanyuan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology","place":["Wuhan, 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