New data suggest NAD plays an even larger role in the anti-aging story than was previously understood

New data suggest NAD plays an even larger role in the anti-aging story than was previously understood

By: Amy Boileau, PhD, RD

Major news outlets around the world such as Time, Men’s Health and New York Post are reporting on new research findings connecting NAD+ levels with anti-aging, that even NASA is interested in. The study results, published in the journal Science, provide compelling evidence of another role for NAD+ in promotion of DNA repair in cells during aging.1 In fact, the reparative effects were so remarkable that one of the investigators stated, “They could not tell the difference between the tissues from an old mouse that is two years old, versus a young mouse that is three to four months old.”2

WHAT IS NAD?

NAD is critical for energy metabolism and DNA repair.3 Cellular NAD+ and its metabolites are important for combating age-related damage to DNA, and other compounds in the body such as proteins and lipids that make up healthy cell structures.4 Because NAD+ declines as we age5, scientists worldwide have been working to figure out ways to maintain or even boost NAD+ in cells.

NAD+ IS ESSENTIAL FOR HEALTHY CELLULAR FUNCTION

Over the last decade, researchers have contributed new published discoveries that have helped us increase our understanding of why and how NAD+ is essential for cellular functioning, and what happens to these functions as part of the normal aging process. These latest findings in Science, suggest that NAD+ is directly regulating the ability of the cell to repair DNA by preventing the formation of a protein complex called DBC1-PARP1. We like PARP1, because it is an enzyme involved in DNA repair. PARP1 also needs NAD+ to be present to do its job. When DBC1 attaches to PARP1, it can’t perform its work repairing DNA. Put another way, DBC1 is like the “off” switch for PARP1.

The investigators showed that older mice had higher concentrations of this DBC1-PARP1 complex and they also had lower levels of NAD+ in their livers. When the mice were given an NAD+ precursor (or booster) called NMN, they saw reduced levels of the DBC1-PARP1 complex, higher levels of NAD+, and reduced amounts of DNA damage – all of which are good things.  While this observation is not surprising, the paper offers us yet another possible explanation as to why DNA repair decreases with aging. The study also makes us optimistic because the investigators also found that this age-related problem could be reversed in the mice by providing NMN.

NMN BOOSTS NAD+ BY BECOMING NR FIRST

Research published late last year in the journal Nature Communications taught us more about how supplemented NMN is able to boost NAD+. Study results explained that when NMN is given, NMN must be broken down into a different NAD+ precursor called nicotinamide riboside (NR), so it can enter the cell, and ultimately become NAD+.6 This needs to occur because the molecular structure of NMN prevents it from directly crossing the cell membrane – at least that is what the published research to date suggests.6

NMN to NR phosphate

SO, DOES THIS MEAN NMN IS ‘IT’?

There are a number of known NAD+ precursors. Most are forms of vitamin B3, including: niacin (NA), nicotinamide (NAM), and nicotinamide riboside (NR). The other is tryptophan, but tryptophan has been found to be significantly less efficient than some of the vitamin B3 alternatives.7 While the recent Science publication did demonstrate that NMN has the ability to increase NAD+ levels in mice, NMN has not been studied in humans, so we don’t yet know how effective it will be at boosting NAD+ in people. That may be a logical next step in the research.

Such research already exists for NR. A team of researchers, headed by Charles Brenner, PhD, the Roy J. Carver Chair of Biochemistry at the University of Iowa Carver College of Medicine, published their study findings last fall in Nature Communications. This research demonstrated that NR increases NAD+ levels in both animals and humans,8 which was an exciting finding given that NR is readily available, and its safety data has been reviewed by the Food and Drug Administration (FDA).

FINAL THOUGHTS

This new research can be interpreted as the discovery of yet another way in which cellular NAD+ levels are important to healthy aging. We love seeing experiments that advance our knowledge of the important role of NAD+ and how it helps to extend healthspan (the collective years spent in good health).8, 9 This study also provides an explanation as to why both NMN and NR might be effective NAD+ precursors.

References

  1. Watson, A., et al., Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration and Is Suppressed in Human Thoracic Aortic Aneurysm Disease. Circ Res, 2017.
  2. Park, A., Scientists Can Reverse DNA Aging in Mice. Time, 2017.
  3. Chini, C.C., M.G. Tarrago, and E.N. Chini, NAD and the aging process: Role in life, death and everything in between. Mol Cell Endocrinol, 2016.
  4. Tempel, W., et al., Nicotinamide riboside kinase structures reveal new pathways to NAD+. PLoS Biol, 2007. 5(10): p. e263.
  5. Zhu, X.H., et al., In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A, 2015. 112(9): p. 2876-81.
  6. Ratajczak, J., et al., NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nat Commun, 2016. 7: p. 13103.
  7. Zhou, C.C., et al., Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol, 2016. 173(15): p. 2352-68.
  8. Trammell, S.A., et al., Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. J Nutr, 2016. 146(5): p. 957-63.
  9. Hamity, M.V.W., S. R.; Walder, R. Y.; Schmidt, M.S.; Brenner, C.; Hammond, D. L., Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats. Pain, 2017. In press.
 


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