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NAD+: A new Strategy to Combat Human Aging?

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Review of “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice” from Cell Metabolism by Stuart P. Atkinson

The road to finding the “elixir of youth” is a long and windy road with dead-ends and circular tracks on every side. However, some exciting research has demonstrated that enhanced biosynthesis of the nicotinamide adenine dinucleotide (NAD+) coenzyme can indeed extend lifespan in yeast, worms, and flies [1-3]. In rodents and humans, NAD+ content declines throughout the body as a function of increasing age, so suggesting that enhancing NAD+ biosynthesis may represent an effective means to retard the aging process. 

Now, a new study from the laboratories of Jun Yoshino and Shin-ichiro Imai has revealed that long-term oral administration of nicotinamide mononucleotide (NMN), a key NAD+ intermediate, can ameliorate signs of  physiological aging in mice [4]. Could this study represent the first step towards the discovery of a new strategy to combat human aging?

To mimic a protocol translatable to humans, the study utilized low-dose NMN in water to treat chow-fed wild-type C57BL/6N mice over a one-year period. This method permitted rapid NMN absorption and transportation and the conversion of NMN to NAD+ within major metabolic tissues. Excitingly, heightened NAD+ levels correlated with the inhibition of age-associated body weight gain observed in regularly fed mice but did not produce any obvious deleterious side-effects. 

However, the study also noted more substantial improvements, including enhanced energy metabolism and general locomotor activity during night intervals, amelioration of age-associated decline in insulin sensitivity, reduced plasma lipid levels, improved eye function, heightened bone density, and  a more youthful myeloid-lymphoid composition. At the molecular level, NMN supplementation appeared to prevent age-associated gene expression changes in a tissue-specific manner and via the induction of two mitochondrial alterations in skeletal muscle; mitonuclear protein imbalance and mitochondrial oxidative metabolism.

Luckily, the study closed with an assessment of which foodstuffs are jam-packed with NMN goodness! So take this paper home and tuck into a bowl of edamame, broccoli, cucumber, cabbage, avocado, and tomato as a new strategy to combat human aging!

References

  1. Anderson RM, Bitterman KJ, Wood JG, et al. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J Biol Chem 2002;277:18881-18890.
  2. Balan V, Miller GS, Kaplun L, et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J Biol Chem 2008;283:27810-27819.
  3. Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell 2013;154:430-441.
  4. Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab 24:795-806.