This peer-reviewed study demonstrates that intranasal GHK-Cu administration produces sustained cognitive improvements in aged mice across both sexes, while intraperitoneal dosing shows inconsistent results. The intranasal route suppressed oxidative phosphorylation and MYC pathways—key aging mechanisms—while reducing glial activation markers (GFAP) and increasing synaptic density (synaptophysin), suggesting direct brain engagement. The findings establish delivery route as critical to GHK-Cu efficacy and provide mechanistic validation for intranasal dosing as a gerotherapeutic approach to age-related cognitive decline.
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Intranasal GHK-Cu showed more consistent cognitive benefit in aged mice than IP dosing; delivery route may matter when counseling patients on administration.