In the aged C57BL/6J mouse model of IR induced by a high-fat diet, SIRT1 improved mitochondrial function via the SIRT1-AMPK-PGC-1α axis and the neuronal differentiation 6 (NeuroD6)-PGC-1α-SIRT1 axis to enhance cognitive decline [102]. This evidence concerns the gene PPARGC1A and Mental deterioration.