Summary: A large-scale dietary trial has shown that a green-Mediterranean diet can slow brain aging by altering key blood proteins linked to neurodegeneration. Using MRI scans and proteomic profiling, researchers tracked nearly 300 participants over 18 months and found that diet significantly shaped the brain age gap.
Two proteins, Galectin-9 and Decorin, emerged as strong indicators of accelerated brain aging but were reduced by the polyphenol-rich green-MED diet. These findings highlight the potential of diet-based strategies to modulate biological pathways tied to Alzheimer’s and age-related cognitive decline.
Key Facts
Brain Age Gap: MRI-based “brain age” can be younger or older than actual age, reflecting brain health.Protein Targets: Galectin-9 and Decorin linked to accelerated brain aging and Alzheimer’s risk.Dietary Effect: Green-MED diet lowered harmful protein levels and slowed brain aging.
Source: Ben-Gurion University of the Negev
A new study led by researchers from Ben-Gurion University of the Negev, Harvard University, and the University of Leipzig has uncovered innovative biological evidence that diet can directly influence brain aging.
Published in Clinical Nutrition, the study examined brain MRI scans alongside detailed blood protein profiles (proteomics) over an 18-month dietary intervention.
The research identified specific proteins linked to accelerated brain aging, with blood levels that were altered following dietary intervention.
Understanding Brain Age Gap
Age-related neurodegenerative conditions, such as brain atrophy, do not always align with our chronological age. Factors such as diabetes, inflammation, hypertension, high cholesterol, and the accumulation of β-amyloid and tau proteins can speed up brain aging. The “brain age gap” is defined as the difference between a person’s MRI-predicted brain age and their actual chronological age.
A positive gap indicates an older brain age than expected – signifying accelerated brain aging – while a negative gap reflects a younger brain age, suggesting a slowdown in brain aging.
A higher brain age gap has been observed in various neurological conditions, including mild cognitive impairment and Alzheimer’s disease.
The DIRECT PLUS Trial – One of the World’s Largest Brain MRI Dietary Studies
The DIRECT PLUS trial is one of the most extensive and longest-running brain MRI intervention studies to date, involving nearly 300 participants divided into three dietary groups. Whole-brain MRI scans were performed before and after the 18-month trial to track changes in brain health.
Using advanced brain-age prediction models based on brain MRI data, researchers estimated each participant’s brain age before and after the dietary intervention.
Previous studies, published in The American Journal of Clinical Nutrition, revealed that both the traditional Mediterranean diet and the green-Mediterranean diet slowed age-related brain atrophy by approximately 50% within 18 months. In addition, improved glycemic control – particularly reductions in HbA1c – also contributed to this protective effect.
The Role of Blood Proteins
The present study investigated whether changes in blood proteomic profiles (a panel of approximately 90 proteins) differed between participants with distinct brain aging trajectories, and whether these differences were influenced by diet. The findings showed that participants whose brain age was older than their chronological age exhibited distinct shifts in their blood protein profiles over the 18 months of the intervention.
Two proteins – Galectin-9 and Decorin – emerged as especially relevant to accelerated brain aging. Their levels significantly decreased among participants following the green-Mediterranean diet, which includes green tea and the aquatic plant Mankai. This suggests a potential beneficial impact on biological processes related to brain aging through blood protein modulation.
The study’s lead researcher, Prof. Iris Shai of Ben-Gurion University, an adjunct professor at Harvard University and an honorary professor at Leipzig University, explains: “This research represents an advance in the field of nutri-omics – the integration of nutrition science with omics technologies such as proteomics – and opens new pathways for developing targeted dietary strategies to slow the progression of neurological diseases.”
Green-MED Diet Targets Key Proteins Driving Brain Aging
There is evidence that Galectin-9, a protein from the Galectin family, is expressed in microglial cells in the brain and that, upon binding to the Tim-3 receptor, it may induce the production of pro-inflammatory cytokines, which may accelerate neurodegenerative processes in diseases like Alzheimer’s. Elevated levels of Galectin-9 have been found in individuals with mild cognitive impairment and in the early stages of Alzheimer’s disease.
Decorin is a structural protein of the extracellular matrix. High levels of Decorin in cerebrospinal fluid have been linked to early changes in Alzheimer’s disease.
Dafna Pachter, a Ph.D. student and the first author of the paper, adds: “In this study, we are taking a small step toward a new possibility – a simple, accessible, and affordable blood test that could, in the future, provide an indication of brain status by analyzing omics layers in the blood”.
In the current study, the green-MED diet, rich in polyphenols from sources such as Mankai, green tea, and walnuts, significantly reduced Galectin-9 levels and slowed the increase in Decorin. The anti-inflammatory activity of these components may explain the potential neuroprotective effect observed in the study.
Dr. Anat Yaskolka-Meir, postdoctoral research fellow at Harvard T.H. Chan School of Public Health and the co-first author of the paper, explains the importance of studying circulating proteomics in brain health: “Studying the circulating proteins in blood allows us to observe, in a real-life setting, how the brain’s aging processes are influenced by lifestyle and dietary changes.
“This approach gives us a dynamic window into brain health, helping to reveal biological changes long before symptoms may appear. By mapping these protein signatures, we gain powerful new insight into how interventions, such as diet, may help preserve cognitive function as we age.”
Funding: The DIRECT PLUS trial was supported by the German Research Foundation (DFG), the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnuts Commission. The funding bodies had no role in study design, data collection, analysis, interpretation, or publication.
Authors: Dafna Pachter*, Anat Y Meir*, Alon Kaplan, Gal Tsaban, Hila Zelicha, Ehud Rinott, Gidon Levakov, Ofek Finkelstein, Ilan Shelef, Moti Salti, Frauke Beyer, Veronica Witte, Nora Klöting, Berend Isermann, Uta Ceglarek, Tammy R Raviv, Matthias Blüher, Michael Stumvoll, Dong D. Wang, Frank B Hu, Meir J Stampfer, Galia Avidan, and Iris Shai. (*Equal contribution)
About this diet and brain aging research news
Author: Ehud Zion Waldoks
Source: Ben-Gurion University of the Negev
Contact: Ehud Zion Waldoks – Ben-Gurion University of the Negev
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial” by Iris Shai et al. Clinical Nutrition
Abstract
Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial
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.
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