Brain aging shows nonlinear transitions, suggesting a midlife "critical window" for metabolic intervention
Antal B, Nieuwenhuizen H, Chesebro A, Strey H, Jones D, Clarke K, Weistuch C, Ratai E, Dill K, Mujica-Parodi L (2025) Proceedings of the National Academy of Sciences of the USA Mar 11;122(10) doi: 10.1073/pnas.2416433122
Web URL: Read this article on PubMed
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 GLUT4 (insulin-dependent glucose transporter) and APOE (lipid transport protein). Notably, MCT2 (a neuronal, but not glial, ketone transporter) emerges as a potential counteracting factor by facilitating neurons' energy uptake independently of insulin. Consistent with these results, an interventional study of 101 participants shows that ketones exhibit robust effects in restabilizing brain networks, maximized from ages 40 to 60, suggesting a midlife "critical window" for early metabolic intervention.FAB RESEARCH COMMENT:
For the related news article please see:
Food and Behaviour Research is a registered charity (No SC034604) and a company limited by guarantee (Co No SC 253448)
Newsletter Signup
Useful Links
Contact Us
FAB Research
23 Carlton Road
Oxford
OX2 7SA
Important Notice
Medical opinion and guidance should always be sought for any symptoms that might possibly reflect a known or suspected disease, disorder or medical condition. Information provided on this website (or by FAB Research via any other means) does not in any way constitute advice on the treatment of any medical condition formally diagnosed or otherwise.
Site by Redstone Websites. Easy to Use Web Content Management. 2026 © All Rights Reserved.