In the past decade, increasing bodies of evidence have demonstrated that systemic decline in NAD+ levels is a key driving force of aging in the field of aging and longevity research. Thus, an anti-aging intervention that aims to increase and maintain NAD+ levels in multiple tissues, called “NAD+ boosting”, has drawn a significant attention in the scientific community and even in general public. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been proven to show significant anti-aging effects in mice and has also been reported to show interesting beneficial effects in several human clinical trials (e.g. Yoshino, M., Yoshino, J. et al., Science, 2021). Our previous study has demonstrated that a subset of neurons in the lateral hypothalamus (LH) that express Slc12a8, a specific NMN transporter, regulates skeletal muscle structure and function through the sympathetic nerve-b2 adrenergic receptor (b2AR) axis, counteracting age-associated sarcopenia and frailty (Ito et al., Cell Rep., 2022). Interestingly, we have recently found that Slc12a8 is also highly expressed in the lateral septum (LS), and knocking out Slc12a8 specifically in the LS causes defects in cognitive flexibility. Furthermore, we have found that NMN stimulates rapid eye movement (REM) sleep by activating GABAergic neurons expressing Slc12a8 in the supramammillary (SuM) nucleus. By juxtacellular recording in the SuM, we have identified bursting slow-oscillation (SO) neurons that are active and discharge in rhythmic theta burst at maximal rates during REM. Their firing frequency significantly decreases in aged mice, and NMN restores the firing frequency to the level of young mice. The Slc12a8-deficient mice show defects in NMN response, decreased percent theta power during REM sleep, and impaired novel object recognition. Optogenetic stimulation of the SuM GABAergic neurons projecting the cortex triggers cortical SO and theta rhythm, recapitulating the effect of NMN. With all these new exciting results, we are now speculating that NMN plays a crucial role in the regulation of specific subsets of neurons in the brain, coordinating and maintaining multiple brain functions during aging.