{"title":"[NAD<sup>+</sup> metabolism as a target for anti-aging].","authors":"Hitoshi Uchida, Takashi Nakagawa","doi":"10.1254/fpj.24072","DOIUrl":null,"url":null,"abstract":"<p><p>Aging is a physiological process caused by various genetic and environmental factors. Recently, it has been proposed that the disturbance of the nutritional-metabolic sensing pathway is one of the aging characteristics. In particular, nicotinamide adenine dinucleotide (NAD<sup>+</sup>) plays an important role in this pathway and is considered the regulator of aging. NAD<sup>+</sup> regulates an energy metabolism as a co-factor and is also involved in various biological processes including transcription, stress responses, DNA repair, inflammatory responses as well as post-transcriptional modifications, as a substrate for sirtuins, poly ADP-ribose polymerase (PARP), and CD38. With age, DNA damage and chronic inflammation increase in organs, resulting in overconsumption of NAD<sup>+</sup> via PARP and CD38. The reduced NAD<sup>+</sup> levels decrease the activity of sirtuins and PARPs and impair energy metabolism, ultimately leading to aging and aging-related diseases. However, the precise metabolism of NAD<sup>+</sup> in vivo and the mechanism of how NAD<sup>+</sup> regulates aging remain elusive. Moreover, the clinical application of NAD<sup>+</sup> supplementation therapy is still under development. In this review, we overview the NAD<sup>+</sup> metabolism and its relation to aging. In addition, we describe the current issue and perspective of NAD<sup>+</sup> supplementation therapy to promote a healthy lifespan.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"268-273"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia Pharmacologica Japonica","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1254/fpj.24072","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Aging is a physiological process caused by various genetic and environmental factors. Recently, it has been proposed that the disturbance of the nutritional-metabolic sensing pathway is one of the aging characteristics. In particular, nicotinamide adenine dinucleotide (NAD+) plays an important role in this pathway and is considered the regulator of aging. NAD+ regulates an energy metabolism as a co-factor and is also involved in various biological processes including transcription, stress responses, DNA repair, inflammatory responses as well as post-transcriptional modifications, as a substrate for sirtuins, poly ADP-ribose polymerase (PARP), and CD38. With age, DNA damage and chronic inflammation increase in organs, resulting in overconsumption of NAD+ via PARP and CD38. The reduced NAD+ levels decrease the activity of sirtuins and PARPs and impair energy metabolism, ultimately leading to aging and aging-related diseases. However, the precise metabolism of NAD+ in vivo and the mechanism of how NAD+ regulates aging remain elusive. Moreover, the clinical application of NAD+ supplementation therapy is still under development. In this review, we overview the NAD+ metabolism and its relation to aging. In addition, we describe the current issue and perspective of NAD+ supplementation therapy to promote a healthy lifespan.