Nicotinamide phosphoribosyltransferase as a key molecule of the aging/senescence process
Document Type
Article
Publication Date
4-1-2021
Abstract
Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD(+), whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD(+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD(+) production through the NAD(+) salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD(+) is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD(+) precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD(+) biosynthesis pathways in mammals, the NAD(+) salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD(+), have been developed so far. In this review, we will focus on the importance of NAD(+) and the possible application of an activator of NAMPT to promote successive aging.
Keywords
NAD(+), NAMPT, NMN, NR, NMNH, aging, senescence, SBI-797812, PNGL, IRW
Divisions
cebar
Funders
Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) (17K08569)
Publication Title
International Journal of Molecular Sciences
Volume
22
Issue
7
Publisher
MDPI
Publisher Location
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND