Brain aging shows nonlinear transitions, suggesting a midlife "critical window" for metabolic intervention.

ABSTRACT: Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal "landmarks" of brain aging starting in midlife (40s). Comparison of metabolic, vascular, and inflammatory biomarkers implicate dysregulated glucose homeostasis as the driver mechanism for these transitions. Correlation between the brain's regionally heterogeneous patterns of aging and gene expression further supports these findings, selectively implicating GLUT

SUBMITTER: Antal BB 

PROVIDER: S-EPMC11912423 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature