NAD+

or Nicotinamide adenine dinucleotide is a coenzyme central to metabolism.

Found in all living cells as an essential element of the biological processes that make life possible. NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other nicotinamide.

In general, NAD+ has two sets of reactions within the human body, helping turn nutrients into energy – a key player in metabolism, and as a supporting molecule for proteins that regulate other biological activities. These important processes are responsible for regulating oxidative stress and circadian rhythms while maintaining the health of the DNA.

“NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins, and maintain mitochondrial fitness through mechanisms... This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer.” (1)

Two important roles NAD has within the human body:   

• helping to convert nutrients into energy and playing a key role in body metabolism
• regulating the cell's aging process via the sirtuin protein.

Is there a relationship between NAD + levels and our age:

• The level of NAD + markedly declines with age, creating an energy deficit that decreases the body’s ability to retain youthful function. The process of aging is related to the process of NAD+ decrement
• By age 50, the level of NAD+ in a typical adult drops to half; by age 80, the NAD+ level drops to only 1% to 10% expressed in youth

(Published in the March issue of Science, Arthur Kornberg won the Nobel Prize for his discovery of NAD synthase, which is part of the award-winning speech.)

What is this "Anti-Aging Mechanism":

• NAD+ activates longevity factors. Maintains the telomer length which in turn prolongs life.

• NAD+ promotes DNA repair. 

• NAD+ regulates immune and inflammatory pathways.

• NAD+ improves chromosomal stability and reduces cancer risk.

“Conversion of our fuels, protein, fat, and carbohydrate into energy requires NAD. Similarly, maintaining our blood glucose at night and generating ketones requires NADH. It’s actually reoxidised as NADH to NAD+. NADH is also re-oxidized to NAD+ when we make ATP from that fuel that we ate. This is required for all of our muscles to work, and for ideas to be transmitted along our nerves, and for us to hear.”  -  University of Iowa Dr. Charles Brenner, PhD.

In 1958, the scientist's Jack Preiss and Philip Handler defined what’s now known as the Preiss-Handler pathway, the pathway demonstrating how nicotinic acid becomes NAD+, providing scientists with further understanding in the role of NAD+ and diet.

Handler’s work largely focused on malnutrition and its role in disease later earned him the National Medal of Science from President Ronald Reagan, who cited Handler’s “outstanding contributions to biomedical research...furthering the state of American science.”

Our current understanding of the importance of NAD+ really began in the 1960s where research established the concept of PARPs, or poly (ADP-ribose) polymerases, a group of proteins that rely on NAD+ to function and regulate DNA maintenance, among other biological functions. PARPs are similar to another group of proteins called sirtuins which both only function in the presence of NAD+.

With Age the supply of NAD+ declines

The first study showing this decline was in 2012, it examined the human skin and established that the coenzyme as vital to aging research.

“This study reports for the first time a link between oxidative stress and PARP activity, aging, and a decline in NAD+ levels, in human tissue. The observed correlation between NAD+ levels and aging adds weight to the idea that NAD+ may play a role in cell senescence and longevity and not simply as an electron carrier.” (2)

In 2015, another human study furthered evidenced the importance of NAD+ demonstrating a decline in levels within the human brain.

“The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompanies the normal aging process but also, elucidates the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.” (3)

Recent studies in animals treated with NAD+ precursors show promise of further potential opportunities for humans with a 2013 study in mice demonstrating that increased NAD+ levels could restore mitochondrial function, while a 2018 study out of MIT promoted the growth of blood vessels and muscles in elderly mice thanks to NAD+ activated sirtuins. 

With more to discover, Scientists are continuing to uncover how far NAD+ can go when it comes to the health of the human body and to date signs point to a promising future.

Not only is NAD+ a key co-enzyme that every cell of our bodies depends on to fuel all the basic functions, it plays a vital role in communicating between the cell nucleus and the Mitochondria to power all activity within our cells. (4)(5)(7)

Scientists have now confirmed a direct link between falling NAD+ levels and aging demonstrating how decreasing NAD+ impairs the cell's ability to produce energy, leading to aging and disease - perhaps even the key factor in why we age. (5)(6)(8) 

REFERENCES

(1)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487780/
(2)  Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue, Published: July 27, 2012, https://doi.org/10.1371/journal.pone.0042357
(3)  In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci USA. 2015 Mar 3;112(9):2876-81. doi: 10.1073/pnas.1417921112. Epub 2015 Feb 17.
(4)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204926/
(5)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076149/
(6)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204926/
(7)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487780/
(8)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407129/[/vc_column_text][/vc_column][/vc_row]