Oxidative stress and decreased DNA-damage repair in vertebrates increases with age also due to lowered cellular NAD+. NAD+ depletion may play a major role in the ageing process at the cellular level by limiting (1) energy production, (2) DNA repair and (3) genomic signalling. Here we hypothesize that it is not the NAD+ as cofactor in redox reactions and coenzyme in metabolic processes that has the ultimate role in ageing, but rather the role of NAD+ in cellular signalling when used as substrate for sirtuins (SIRT1-7 in mammals) and PARPs (Poly(ADP-ribose) polymerases). Both sirtuins and PARPs influence many transcription factors and can affect gene expression. As a signalling molecule NAD+ is consumed in the reaction donating ADP-ribose and releasing nicotinamide (NAM) as a by-product. It seems that ageing at the cellular level is associated with a decline of NAD+ and that NAD+ restoration can reverse phenotypes of ageing by inducing cellular repair and stress resistance. Adequate intracellular NAD+ concentrations may be an important longevity assurance factor while lowered cellular NAD+ concentration may negatively influence the lifespan.
This research output has an Altmetric Attention Score of 32. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 September 2026.
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