Bamboo XZ Yan, WeiGuo Lao, Chi Zhang, Thombas Ebjer and Hina Asrar*
NAD+ , a linchpin for mitochondrial function, is crucial in protecting the body from aging and related diseases. The reduced biosynthesis and increased activity of NAD+ consuming enzymes lower cellular contents of NAD+ with aging. Since the homeostasis of the NAD+ pools is vulnerable to biological aging, and thus, raises a serious concern for the healthcare staff to cure age-related disorders. Replenishing NAD+ pools with the administration of relevant supplements rescues the depleting cellular NAD+. Accordingly, the small-scale human clinical trials have shown ameliorative effects of exogenous NAD+ in treating age-related disorders. However, validation of these studies requires considerable time. Therefore, investigations on a rapid and targeted influx of NAD+ are fundamental to achieving the benefits offered by the science of anti-aging. One possible strategy is the oral administration of intact NAD+ molecule followed by its forced localization to the mitochondria as an elixir of longevity. Integration of the recent findings with previous studies to dissect the trafficking of intracellular NAD+ will direct to a heuristic approach to extending individual lifespan. Here we present a critical analysis of the current status of therapeutic interventions to enhance intracellular NAD+ while highlighting the controversial studies and gaps in the same field. This review emphasizes using a connexion (Cx43) and mitochondrial carrier family (SLC25A51) as the chief NAD+ transporters and the possible erspectives to translate this knowledge for better mitochondrial efficiency. We propose a strategy based on an improved influx of mitochondrial NAD+ that will restore the redox and non-redox functions of NAD+. This understanding may establish a foundation to smartly deal with situations where the inability to import the supplemented NAD+ is the prime cause of mitochondria performance-related diseases.
Published Date: 2022-07-26; Received Date: 2022-06-28
