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A massive human study has uncovered how genetics shape the pace of brain aging. By combining MRI scans, genomic data, and machine learning, researchers identified 59 genetic regions that influence how quickly the brain grows old, revealing strong links to blood pressure, diabetes, and Alzheimer’s disease.
The Discovery:
In the largest brain-aging genetics study to date, scientists analyzed MRI and genomic data from more than 56,000 people across multiple cohorts. They used advanced machine learning models to calculate each person’s “brain age gap,” the difference between their brain’s biological and chronological age. The results showed that up to 29 percent of this brain aging variation is genetic. The team pinpointed 59 specific genomic loci, 39 of which had never been linked to brain aging before. Among the most important genes were MAPT, known for its role in Alzheimer’s disease, and APOE, the strongest known genetic risk factor for dementia.
The Science:
Researchers trained models on MRI images of gray and white matter to estimate biological brain age with high accuracy (error margin around 3 years).
Brain age gap values were strongly heritable, with 23 to 29 percent of variance explained by common genetic variants.
A total of 59 genomic regions were linked to brain aging. Thirty-nine of them were completely new discoveries.
Key genes include MAPT (tau protein and Alzheimer’s pathology), APOE (lipid transport and neuronal repair), KCNK2 (potassium channel involved in neuroinflammation and brain barrier integrity), and DPF3 (a chromatin remodeling factor tied to neurogenesis).
Genetic pathways connected brain aging to immune system regulation, neurodevelopment, and small GTPase signaling, which acts as a cellular timing mechanism.
Mendelian randomization analysis revealed that high blood pressure and type 2 diabetes causally accelerate brain aging, adding roughly half a year of biological brain age per standard deviation increase in blood pressure.
Brain aging showed shared genetic architecture with depression, cognitive decline, cardiovascular disease, alcohol intake, smoking, and socioeconomic traits such as income and education.
Your Action:
New gene-editing and gene-therapy approaches are emerging to slow or even reverse brain aging by targeting the genetic and cellular pathways behind it. While these treatments are still in development, their progress marks the beginning of a new era in brain rejuvenation science.
For now, protect your brain through actions proven to keep it biologically younger. Maintain healthy blood pressure and glucose, lower inflammation, stay physically active, eat nutrient-rich foods, and get regular restorative sleep. These habits slow biological brain aging and strengthen overall longevity.
Bottom Line:
Your brain’s biological age is partly written in your DNA, but your lifestyle can slow how fast that script unfolds.
Source:
Genome-wide analysis of brain age identifies 59 associated loci and unveils relationships with mental and physical health, Nature Aging, Philippe Jawinski et al., Humboldt University of Berlin, Leipzig University, Broad Institute, Max Planck Institute for Human Cognitive and Brain Sciences.
https://doi.org/10.1038/s43587-025-00962-7
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