A systems-approach to NAD+ restoration

Nichola Conlon*, Dianne Ford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

A decline in NAD+ is a feature of ageing and may play a causal role in the process. NAD+ plays a pivotal role in myriad processes important in cellular metabolism and is a cosubstrate for enzymes that play key roles in pathways that modify ageing. Thus, interventions that increase NAD+ may slow aspects of the ageing trajectory and there is great interest in pharmacological NAD+ restoration. Dietary supplementation with NAD+ precursors, particularly nicotinamide riboside, has increased NAD+ levels in several human intervention studies and arguably been the most robust approach to date. However, consistency and reliability of such approaches to increase NAD+, and also impact on markers of efficacy to slow or reverse features of ageing, has been inconsistent. We argue that a major element of this variability may arise from the use of single-target approaches that do not consider the underlying biological complexity leading to NAD+ decline. Thus, a systems approach – targeting multiple key nodes in the NAD+ interactome – is likely to be more efficacious and reliable.
Original languageEnglish
Article number114946
Number of pages11
JournalBiochemical Pharmacology
Volume198
Early online date5 Feb 2022
DOIs
Publication statusPublished - 1 Apr 2022

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