On one hand, increasing cellular NAD+ levels in non-senescent cells can suppress the transition to senescence by reducing DNA damage and mitochondrial dysfunction. On the other hand, increased NAD+ levels could actually enhance SASP by encouraging sensecent cells to develop the SASP, as well as increasing pro-inflammatory cytokine production in cells that already have the SASP.[1]
Research has shown that the resulting increased level of pro-inflammatory cytokines produced by senescent cells with SASP lead to increased levels of the NAD+ consuming enzyme CD38 in neighboring cells. This has the effect of reducing NAD+ levels in normal cells nearby senescent cells with the SASP.[2][3][4] When NAD+ levels are reduced in the normal, non-sensescent cells, mitochondrial dysfunction and the accumulation of DNA-damage can in-turn promote the development of senescence.[1]
Thus, the theoretical concern is that increasing NAD+ levels, in spite of all of the healthy / anti-inflammatory effects in normal cells, could also increase inflammation while promoting neighboring cells to transtion to sensescence and SASP in a potential viscious cycle. More research is needed to determine whether the potential for NMN supplements to promote SASP is only a theoretical one, or if caution may be warranted for NMN supplementation in certain individuals or populations. Nonetheless, it is important to emphasize the no evidence has been found so far in human clincal trials to date that NMN may promote SASP.