Brain aging shows nonlinear transitions, suggesting a midlife “critical window” for metabolic intervention
This study used MRI and body measures from more than 19,000 people to show that brain activity does not age in a straight line but goes through sharper “turning points,” with a key shift starting in the 40s. Comparison of metabolic, vascular, and inflammatory biomarkers implicates disrupted blood sugar regulation as the main driver of these transitions.
Links between where the brain ages fastest and patterns of gene expression point specifically to GLUT4 (the insulin‑dependent glucose transporter) and APOE (a lipid transport protein). MCT2, a neuronal ketone transporter, appears as a possible protective factor because it lets neurons take up energy without relying on insulin. In a trial of 101 people, giving ketones had strong effects in restabilising brain networks, with the biggest impact between ages 40 and 60, suggesting a midlife “critical window” for early metabolic intervention.
SOURCE: PNAS
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