Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs.

Mice aged 20-21 months, roughly equivalent to middle-aged or older humans, were given the peptide GHK-Cu, a copper-bound compound that occurs naturally in the body. One group received it by injection into the abdomen for 5 days, and another group received it as nose drops for 8 weeks. The researchers measured how quickly the mice learned to find a hidden platform in a water maze, a test of memory and learning. They also looked at brain tissue under a microscope and analyzed which genes were switched on or off in the hippocampus, a brain area key for memory. The paper reports that nose-drop treatment improved learning in both male and female mice, while injection only briefly helped males and not females. The two delivery methods also changed different sets of genes: nose drops turned down energy-producing and growth-related pathways, while injections turned up repair and stress-response pathways. The authors conclude that both routes improved learning, but through different biological mechanisms, and that the way a drug is given matters for how it works in the aging brain.

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