Suffolk Reporter

A recent study published in PNAS highlights critical transition points in brain aging, suggesting new opportunities for preventing cognitive decline. Conducted by an international team led by Lilianne R. Mujica-Parodi from Stony Brook University, the research analyzed brain networks in over 19,300 individuals using large-scale datasets.

The findings indicate that brain network degradation follows an S-shaped curve with distinct transition points, contrary to previous assumptions of a gradual linear decline or late-life onset. The initial signs of degeneration appear around age 44, accelerate at age 67, and plateau by age 90. This suggests specific windows for effective intervention.

“Understanding exactly when and how brain aging accelerates gives us strategic timepoints for intervention,” said Mujica-Parodi. She noted a "critical midlife window" where neurons experience metabolic stress but remain viable, allowing potential restoration of function through alternative fuels like ketones.

The study identified neuronal insulin resistance as a primary driver of this trajectory. By examining biomarkers and gene expression analyses, researchers implicated insulin-dependent glucose transporter GLUT4 and lipid transport protein APOE in aging patterns. However, the neuronal ketone transporter MCT2 emerged as a protective factor.

This discovery led to an interventional study comparing glucose and ketone administration in participants across different aging stages. Ketones stabilized brain networks effectively during the midlife "metabolic stress" period but showed reduced impact in older adults due to compounding vascular effects.

Mujica-Parodi emphasized that these findings could revolutionize approaches to preventing cognitive decline and diseases like Alzheimer’s by targeting metabolic interventions early on. “This represents a paradigm shift in how we think about brain aging prevention,” added Botond Antal, first author and postdoctoral associate at Stony Brook.

From a public health perspective, these insights may inform new screening guidelines and preventive strategies. Early identification of increasing insulin resistance coupled with targeted interventions could delay cognitive aging significantly.

With dementia cases expected to triple by 2050 amid global population aging, these findings offer hope for maintaining cognitive health into later life.

The research was supported by the W. M. Keck Foundation and the National Science Foundation Brain Research through Advancing Neurotechnologies initiative. It involved collaboration among scientists from Stony Brook University, Massachusetts General Hospital, Mayo Clinic, Oxford University, and Memorial Sloan Kettering.