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Pachter, D.* ; Yaskolka Meir, A.* ; Kaplan, A.* ; Tsaban, G.* ; Zelicha, H.* ; Rinott, E.* ; Levakov, G.* ; Finkelstein, O.* ; Shelef, I.* ; Salti, M.* ; Beyer, F.* ; Witte, V.* ; Klöting, N. ; Isermann, B.* ; Ceglarek, U.* ; Riklin Raviv, T.* ; Blüher, M. ; Stumvoll, M. ; Wang, D.D.* ; Hu, F.B.* ; Stampfer, M.J.* ; Avidan, G.* ; Shai, I.

Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial.

Clin. Nutr. 53, 99-108 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND AND AIMS: We explored whether changes in serum proteomic profiles differed between participants with distinct brain aging trajectories, and whether these changes were influenced by dietary intervention. METHODS: In this secondary analysis of the 18-month DIRECT PLUS trial, 294 participants were randomized to one of three arms: 1) Healthy dietary guidelines (HDG); 2) Mediterranean (MED) diet (+440 mg/day polyphenols from walnuts); or 3) low red/processed meat green-MED diet (+1240 mg/day polyphenols from walnuts, Mankai plant, and green tea). We measured 87 serum proteins (Olink-CVDII). We used Magnetic-Resonance-Imaging (MRI)-assessed 3D-T1-weighted brain scans for brain age calculation (by convolutional neural network) to identify protein markers reflecting the brain age gap (BAG; deviation of MRI-assessed brain age from chronological age). RESULTS: At baseline, lower weight, waist circumference, diastolic blood pressure, and HbA1c parameters were associated with a younger brain age than expected. Specifically, higher levels of two proteins, Galectin-9 (Gal-9) and Decorin (DCN), were associated with accelerated brain aging (larger BAG). A proteomics principal component analysis (PCA) revealed a difference in PC1 between the two time-points for participants with accelerated brain aging. Between baseline and 18 months, Gal-9 significantly decreased among individuals who completed the intervention with attenuated brain aging, while DCN significantly increased among those who completed the trial with accelerated brain aging. A significant interaction was observed between the green-MED diet and proteomics PCA, resulting in a beneficial change compared to the HDG. Participants in the green-MED diet significantly decreased Gal-9 compared to the HDG diet and from baseline. CONCLUSIONS: Higher serum levels of Gal-9 and DCN may indicate an acceleration of brain aging and could be reduced by a green-MED/high-polyphenol (green tea and Mankai) and low-red/processed meat diet. TRIAL REGISTRATION NUMBER: NCT03020186.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Brain Age ; Dietary Interventions ; Peripheral Protein Expression ; Proteomics ; Randomized Controlled Trial; Proteoglycan; Age; Pathology; Cognition; Pathway; Atrophy; Memory; Risk; Beta
ISSN (print) / ISBN 0261-5614
e-ISSN 0261-5614
Journal Clinical Nutrition
Quellenangaben Volume: 53, Issue: , Pages: 99-108 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Journal Production Dept, Robert Stevenson House, 1-3 Baxters Place, Leith Walk, Edinburgh Eh1 3af, Midlothian, Scotland
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Council for Higher Education-Zuckerman support program for outstanding postdoctoral female researchers
Kreitman Doctoral Fellowship at the Ben-Gurion University of the Negev
California Walnut Commission
Israel Ministry of Science and Technology
Israel Ministry of Health
German Research Foundation (DFG)