Could NMN supplementation potentially promote or enhance SASP?

    Last Updated: May 14, 2024

    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.

    References

    1. ^Chini CCS, Cordeiro HS, Tran NLK, Chini ENNAD metabolism: Role in senescence regulation and aging.Aging Cell.(2024 Jan)
    2. ^Chini C, Hogan KA, Warner GM, Tarragó MG, Peclat TR, Tchkonia T, Kirkland JL, Chini EThe NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD(+) decline.Biochem Biophys Res Commun.(2019 May 28)
    3. ^Chini CCS, Peclat TR, Warner GM, Kashyap S, Espindola-Netto JM, de Oliveira GC, Gomez LS, Hogan KA, Tarragó MG, Puranik AS, Agorrody G, Thompson KL, Dang K, Clarke S, Childs BG, Kanamori KS, Witte MA, Vidal P, Kirkland AL, De Cecco M, Chellappa K, McReynolds MR, Jankowski C, Tchkonia T, Kirkland JL, Sedivy JM, van Deursen JM, Baker DJ, van Schooten W, Rabinowitz JD, Baur JA, Chini ENCD38 ecto-enzyme in immune cells is induced during aging and regulates NAD(+) and NMN levels.Nat Metab.(2020 Nov)
    4. ^Ugamraj HS, Dang K, Ouisse LH, Buelow B, Chini EN, Castello G, Allison J, Clarke SC, Davison LM, Buelow R, Deng R, Iyer S, Schellenberger U, Manika SN, Bijpuria S, Musnier A, Poupon A, Cuturi MC, van Schooten W, Dalvi PTNB-738, a biparatopic antibody, boosts intracellular NAD+ by inhibiting CD38 ecto-enzyme activity.MAbs.(2022 Jan-Dec)