Remarkably, blocking MT1-MMP specifically in the hippocampus phenocopied the learning and memory improvements seen in Mmp14+/− mice with obesity (Supplementary Fig. S8j–m), suggesting that hippocampal MT1-MMP negatively regulates cognitive function in both aging and obesity, and this effect can be reversed by pharmacological MT1-MMP inhibition. The gene discussed is MMP14; the disease is obesity due to melanocortin 4 receptor deficiency.