A decline in NAD+ is a feature of aging 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 aging, 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.

The understanding of the molecular and cellular basis of aging has grown exponentially over recent years, and it is now accepted within the scientific community that aging is a malleable process; just as it can be accelerated, it can also be slowed and even reversed. This has far-reaching implications for our attitude and approach toward aging, presenting the opportunity to enter a new era of cellular regenerative medicine to not only manage the external signs of aging but also to develop therapies that support the body to repair and restore itself back to a state of internal well-being. A wealth of evidence now demonstrates that a decline in cellular nicotinamide adenine dinucleotide (NAD+) is a feature of aging and may play a role in the process. NAD+ plays a pivotal role in cellular metabolism and is a co-substrate for enzymes that play key roles in pathways that modify aging. Thus, interventions that increase NAD+ may slow aspects of the aging trajectory, and there is great interest in methods for cellular NAD+ restoration. Given these recent advancements in understanding the cellular aging process, it is important that there is an integration between the basic scientists who are investigating the underlying mechanisms of cellular aging and the surgeons and aesthetic practitioners who are providing antiaging therapies. This will allow the effective translation of this vastly complex area of biology into clinical practice so that people can continue to not only stay looking younger for longer but also experience improved health and wellness.