Suffolk Reporter

A study published in PNAS reveals new insights into brain aging, identifying critical transition points for potential interventions. The research, led by Dr. Lilianne R. Mujica-Parodi of Stony Brook University, analyzed brain networks in over 19,300 individuals. It found that brain aging follows an S-shaped curve with distinct transition points rather than a gradual decline or late-life onset.

Dr. Mujica-Parodi stated, “Understanding exactly when and how brain aging accelerates gives us strategic timepoints for intervention.” The study highlights a "critical midlife window" where the brain experiences declining energy access but before irreversible damage occurs.

The primary driver of this trajectory is neuronal insulin resistance. Metabolic changes precede vascular and inflammatory ones, with gene expression analyses implicating the insulin-dependent glucose transporter GLUT4 and lipid transport protein APOE in these patterns.

An interventional study compared glucose and ketones' effects on participants at different aging stages. Ketones stabilized deteriorating brain networks effectively during midlife but had diminished impact in older adults due to compounding vascular effects.

Mujica-Parodi suggests these findings could revolutionize approaches to preventing cognitive decline and neurodegenerative diseases like Alzheimer’s. “This represents a paradigm shift in how we think about brain aging prevention,” noted Botond Antal, PhD, Postdoctoral Associate at Stony Brook.

The research emphasizes early identification of increasing insulin resistance in the brain and targeted metabolic interventions as preventive strategies against cognitive aging.

Funded by the W. M. Keck Foundation and NSF's BRAIN Initiative, the work involved scientists from Stony Brook University alongside collaborators from Massachusetts General Hospital, Mayo Clinic, Oxford University, and Memorial Sloan Kettering.