CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves

NAD+ and cognitive hypersensitivity during aging Cognitive dysfunction is one of the most concerning outcomes in global population aging. However, the mechanisms of cognitive impairment during aging remain elusive. We found that in old mice, levels of nicotinamide adenine dinucleotide (NAD+), an essential chemical for all living organisms, declined in the hippocampus, a critical part of the brain for memory and learning. We also found that age-associated hypersensitivity in cognitive and behavioral functions (cognitive hypersensitivity) was induced by reduced NAD+ availability in the hippocampus. Supplementation of nicotinamide mononucleotide (NMN), a critical chemical that is converted to NAD+, is able to mitigate the cognitive hypersensitivity observed in old mice. Our findings provide new insights into how NAD+ decline affects age-associated anxiety/depression and how such impairments can be prevented or treated by enhancing NAD+.