Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial
Clinical Nutrition, 2025
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., Hu F., Stampfer M., Avidan G., Shai I.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Nutritional Science Aging | Pathophysiology | Serum |  Olink Target 96 |
Abstract
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.