BBB (blood-brain barrier)

The blood-brain barrier is not a passive wall but part of the «neurovascular unit», a coordinated ensemble of endothelial cells, pericytes, astrocytes, neurons and extracellular matrix. Its selectivity comes from tight junctions (claudins, occludin, ZO-1) that seal the paracellular space between endothelial cells, preventing water-soluble molecules from slipping through. Transport across the barrier is tightly regulated by specific carriers (GLUT1 for glucose, LAT1 for amino acids) and efflux systems such as P-glycoprotein, which actively pumps xenobiotics back out.

With aging, the BBB becomes leakier: endothelial senescence, pericyte loss, mitochondrial dysfunction and chronic low-grade inflammation (inflammaging) all degrade it. This leakage lets blood proteins, immune cells and neurotoxic debris enter the brain — a mechanism documented in Nature Reviews Neurology as an initiator of neurodegenerative pathways in Alzheimer's and Parkinson's.

In longevity medicine, the BBB is central to intervention design: many compounds simply cannot cross it and require special formulations (magnesium L-threonate, for instance, was engineered precisely because it raises brain magnesium by crossing the barrier). Approaches such as hyperbaric oxygen therapy and modulation of the gut-brain axis are studied for their potential to preserve barrier integrity as we age.