By Vince Giuliano and James P Watson
This entry signals some intended changes in our blogging approach and lists some blog entries we plan to publish soon.
A. Changes in blogging approach
We expect to go to shorter more- focused entries, away from long encyclopedic ones that try to cover everything we know about a topic. Our 8-year history has seen us gradually moving from frequent short entries (one or two computer screens) to relatively infrequent publication of what amounts to dissertations on key topics, perhaps 50-100 normal pages in length and comprising 100 or more citations. This evolution has been somewhat natural for us as we have learned more and more about key topics and have had more and more to say about them. But we are concerned that it also has led to intractable blog entries that are so long and complex that they are extremely difficult to follow and may act to anaesthetize our readers.
We will accomplish this in large part by an approach we have already started – breaking discussions of complex topics like The NAD World, Transposable Elements and Digital Health into more-digestible numbered parts. We will be adding new entries under these established series that are already broken into parts as well as under other new categories.
Most of the accesses to this blog relate to archived rather than the latest entries – and we have published more than 500 of them now. We believe these articles constitute a rich background related to many key sciences that impact health and aging. So, as time progresses we intend to enhance the cross-linking among these items. Up to this time there has only been cross-linking from newer to older articles among those we have already written. So, we will seek to be more diligent in cross-referencing blog entries both backwards as well as providing forward references, at least in the initial paragraphs of older entries. We expect soon to start going back through historical items and adding forward-looking reference links.
We will also list some new blog entries as belonging to two or more series as we see very important linkages. For example the very next blog entry to be published after this one will be #5 in the established NAD World series as well as #1 in a brand new series on Inflammation.
B. Blog entries we expect to publish soon
Stories on Inflammation
The blog entry to follow this one is just about ready to go and entitled Part 5 of the NAD world: the conflicting roles of NAMPT: inflammation or rescue? Also Part 1 on a new series on inflammation, by Jim Watson. Jim has written the following introduction to the inflammation series in a recent e-mail to me:
“I completely agree that we should explain inflammation to our readers through a series of “Stories” with historical and human interest tales to help our readers understand and remember the stories. I will call these stories the “Stories of Inflammation.” These are mainly “molecular stories” about inflammation that could be told separately, or merged into one massive “Grand Unified Theory of Inflammation” (GUTI). As you know, my favorite movie is The Gods Must Be Crazy I (The sequels were not as good). From here on, I will refer to the movie as “TGMBC”. I love the fact that TGMBC movie was actually 4 apparently unrelated stories that were being told in parallel, as 4 separate “video tracks”. The stories were not connected to each other until the very end of the movie, where the bungling terrorists (Sam Boga), the school teacher (Kate Thompson), the Pigmy (Xi), and the Elephant dung scientist (Andrew Steyn) all meet in the same Botswana plain. Here in this field, all of the stories finally merge into one story. There are multiple “story lines” in the story of inflammation. So, the blog entries in the Inflammation series will be the “a molecular equivalent of TGMBC”. It is a “movie about inflammation” with at least 8-10 seemingly unrelated stories – omega-3s, PPARs and their ligands, aspirin, exercise (aka ROS), the PGC -1a co-activator, autophagy, mitochondrial biogenesis, and the necessity of NAD-dependent Sirtuin deacetylation of at least one lysine acetyl group with all of the above (PGC-1a, PPARgamma, etc.) and the next blog which is about extra-cellular NAMPT. For those who like to watch a movie with only one story line, these blog entries could be maddening – but we seek to tell it like it is. The fact that so many drugs and so many researchers only look at “one story” may be a major reason why we have not yet solved the problem of inflammation. I hope this series of blogs will get this point across. – Inflammation is a TGMBC Movie with many stories!”
Here is a sample of three Major Stories of Inflammation (and their components)
1. The inflammatory story of NAD’s two-faced cousin
Here is the story: “There once was (and still is) a wonderful substance that players in the anti-aging game like us want to have more of in our cells because it makes us healthy and maybe even live longer. Called NAD+, publications were written about this great substance by the best of researchers in the greatest temples of longevity research (and, by us in this blog). And supplement makers started selling expensive pills that could trick our cells into making more of this. One of the critical molecules in cells responsible for making NAD+, a close cousin molecule, is called NAMPT, so people in the know started wanting to have more of that too. But then, a dark side of all of this begin to emerge as it was realized that NAMPT was actually a familiar substance, a carpet-bagger that travelled using various aliases, especially outside of cells where it did shocking things. We learned our trusted NAMPT was often behaving inappropriately for its princely role when it is outside ur cells. Not to be trusted, extra-cellularNAMPT, eNAMPT, can be caught creating horrible inflammation and is closely associated with highly disreputable diseases. We have written before about the good side of NAMPT when it is in cells. This blog entry is an exposure of its bad inflammation-generating side of eNAMPT. And it is also about a few of its redeeming features. This story is told in the next blog entry Part 5 of the NAD world: the conflicting roles of NAMPT: inflammation or rescue? Also Part 1 on a new series on inflammation.
2. The “Fish Oil Story” and the misunderstood “Snake Oil Story” of the Wild West
We usually think of “snake oil” as a completely phony and useless health remedy sold by glib traveling con men like the Wizard of Oz, sold off the back of colorful wagons to clueless country folks. “Snake oil is an expression that originally referred to fraudulent health products or unproven medicine but has come to refer to any product with questionable or unverifiable quality or benefit. By extension, a snake oil salesman is someone who knowingly sells fraudulent goods or who is themselves a fraud, quack, or charlatan(ref).” Not necessarily so. In the first instances in China, snake oil was made from real water snakes and had high concentrations of the same omega-3 ingredients found now in concentrated fish oil supplements, EPA and DHA. And it therefore helped control certain forms of inflammation like the fish oil we take today does. . See this article on How Snake Oil got a Bad Rap
Our blog entry will cover:
– how rattlesnake oil (8.5% omega-3s) was used instead of oil from Chinese water snakes (20% omega-3s) by the traveling salesmen of the Wild West
– how scientists initially misunderstood the molecular mechanisms of EPA and DHA as anti-oxidants
– the discovery of the bioactive lipids (Resolvins, Protectins, and Maresins) that are endogenously synthesized by evolutionarily conserved pathways
– the discovery that DHA activates PPARs, but only after being oxidized (i.e. why exercise is needed for activating fish oil)
Conclusion: Resolvins, Protectins, Maresins, Lipoxins, and oxidized DHA are actually the molecular mediators of the health effects of fish oil (and of real Chinese water snake oil) and all of these work by down-regulating inflammation
3. The “Willow Bark Story” and the misunderstood role of low-dose aspirin
– how Hippocrates, the Egyptians, and many ancient civilizations used salicylic acid teas and potions for fever and pain relief
– how willow bark tea was used by the native Americans and early explorers for inflammation
– aspirin, the COX genes and inflammatory diseases such as rheumatoid and osteoarthritis.
– risks and potential benefits of low-dose aspirin
And soon, we expect to publish a blog entry on research reported at the 2016 annual meeting of the International Dose Response Society