IGF-1 is required for young circulation to restore the brain’s protective barrier in aged mice
IGF-1 is required for young circulation to restore the brain’s protective barrier in aged mice
In a study published on August 20, 2026, 18-month-old mice were surgically joined to 4.5-month-old mice so that they shared a circulatory system. Young circulation reduced leakage across the protective barrier between the blood and brain tissue and increased the density of small blood vessels. Both improvements were weaker when IGF-1 levels were reduced in the young mice and its receptor was deleted from the vascular wall of the aged mice.
This procedure is called heterochronic parabiosis. An aged mouse and a young mouse are surgically joined so that they share a circulatory system. In a 2024 study, the same group had already found that the aged partners had a less permeable blood-brain barrier, which separates the blood from brain tissue, and a denser network of capillaries, the smallest blood vessels. The new study examines which signal in the shared blood contributes to these changes.
The authors focused on IGF-1, a signaling protein whose concentration in the blood declines with age. For a blood vessel to respond, the protein must enter the shared circulation, and the vessel’s inner lining, called the endothelium, must receive the signal through the IGF-1R receptor. In one group, IGF-1R was deleted from the endothelium of the aged mouse. In another group, IGF-1 production was reduced in the liver of the young partner.
These interventions test different parts of the same pathway. The researchers assessed the barrier through a transparent window in the skull. They injected fluorescent molecules of different sizes into the blood and observed whether the molecules left the vessels and entered the brain tissue. When IGF-1 or its receptor was deficient, the smallest of these molecules leaked out more readily. The density of capillaries with diameters of up to 10 micrometers also decreased.
Some improvements remained in the groups with altered IGF-1 or IGF-1R. The two interventions disrupt the signal at different points and support the same causal pathway. In this model, IGF-1 in the shared blood and the endothelial response through IGF-1R are required for young circulation to produce the full improvement in barrier integrity and capillary density.