SIRT1 and Mental deterioration: The three strongest lines of evidence in this regard are (1) SIRT1 is important for certain aspects of neural connectivity and synaptic plasticity, (2) Loss or decline in CNS SIRT1 activity occurs during aging, and this deficit is directly associated with defined neurophysiological and neuropathological mechanisms of cognitive decline and metabolic dysfunction; and (3) SIRT1 overexpression in certain neurons in the brain increased lifespan.