By Vince Giuliano
Here is the PowerPoint presentation I made at the 3 rd Annual NAD Summit Conference on January 27 at 2 PM in San Diego. TALES OF NAD+ Just double click on the following link to download it.
The presentation consist of relating a number of stories, tales related to the enzyme NAD+. There are three sets tales I talk about, respectfully FUNDAMENTAL NAD STORIES, tales about THE NAD- CHAMBER OF HORRORS, things that can go wrong in your body if you do not have enough NAD+. And NAD+ PAC-MEN, processes that can eat up your NAD+ while you are not looking. Jim Watson contributed a lot to making this presentation.
These are all stories that are implicit in our published series of blog entries on the NAD world summarized below. Hopefully, they are easier to fathom then as origionally presented in our complex and encyclical blog entries themselves.
The NAD- CHAMBER OF HORRORS tales are about some of the main things that can go horribly wrong if you don’t have enough NAD+ in your body or your NAD+/NADH ratio goes screwy. These include but are not limited to:
- Inadequate production of sirtuins: SIRT1, SIRT6 and SIRT7
- PARP starvation and compromised DNA repair; genomic instability
- Inadequate production of key mitochrondial proteins, mitochondrial dysfunction and death,
- Extensive mitochondria-originated ROS flooding
- Metabolic reprogramming to Warburg metabolism
- Misfolded proteins don’t get cleaned up
Compromised stress resistance
- Histones don’t get adequately deacetylated
- Reduced antioxidant defenses and oxidative damage to proteins
- Deacetylated and inactivated tumor suppressor proteins
- Microtubule railways hijacked, inflammasomes activated, and chronic destructive inflammation
- Cell senescence
- Impaired autophagy
- Endoplasmic reticulum stress
Also, these horror tales include ones about the about downstream consequences of the above factors such as:
- Genesis and persistence of most diseases of aging including cancers, atherosclerosis, diabetes and dementias
- Low energy, tiredness, difficulty focusing
- Hypertension, increased susceptibility to sunburn and skin cancer
- Makes you fat and stupid
- Poor sleep
- Accelerated aging
- Many many other unwanted consequences and forms of suffering
The NAD+ PAC-MEN tales are about processes that can eat up your NAD+ while you are not looking, including
- PARPs (1 and 2)
- SIRTS (1-7)
- CD 38
- NQ01 gene not turned on
- CD157, ART1, ART2, ART3, and ART4; ADP-ribose glycohydrolases
- Warburg metabolism
- High fat diet
- At least 45 additional factors regulate NAD+ levels and SIRT1 levels which are closely related.
I also comment on some things that can be done about a few of the Horror and Pac-Men factors identified. Some of the subjects touched upon include the NAD salvage cycle, futile redox cycling, role of BET proteins, impact of and upon circadian gene regulation, NQO1-mediated PGC-1α protection, NQ01 and P53 stabilization , activation of NQO1 by beta-lapachone, and some of the other ways to turn on the NQ01 gene.
Finally, I comment on the possible reason why IV infusions of NAD may be beneficial when levels of NAD+ are so depleted that oral supplements may not be capable of overcoming the effects of a deleterious positive feedback cycle,
Resistance is not necessarily futile!
If you would like more extensive background, you can review the series of blog entries on the NAD world by Jim Watson and I:
The Part 1 blog entry in the NAD World series provided an overview treatment of the NAD World and its nuances: to identify the major molecular entities involved, their roles, health and longevity ramifications, the reasons for the current excitement, and to begin to clarify what is actually known and what the remaining uncertainties are.
The Part 2 blog entry in the NAD World series concentrates on the reasons for focusing on NAD+, particularly with respect to interventions that are seriously likely to lead to longer healthier lives. It discusses molecular processes in the NAD salvage cycle that are responsible for the health-inducing and life-extending properties of calorie restriction, and further discuss the key roles of Sirtuins, SIRT1, SIRT6 and SIRT7 in particular.
The Part 3 blog entry in the NAD World series identifies 30 Major Factors that Control SIRT1 Expression, SIRT1 Activity, and SIRT1-mediated Aging, the NAD+/NADH ratio and what affects it.
The Part 4 blog entry in the NAD World series is concerned with the NQ01 gene, the Warburg effect, SIRT 1 and inflammation, and possible interventions.
The Part 5 blog entry in the NAD World series is concerned with the conflicting roles of extra-cellular NAMPT, which behaves as both an enzyme and a cytokine, how it is implicated in inducing many disease processes as well as having some positive health impacts.
We expect there will be more such blog entries, in fact we are considering a Part 6 entry that will include: How Google is getting into NAD+ businesss, why Google’s strategy will fail, why NR/NMN/NAD+ will not stop aging.