Nicotinamide riboside supplementation for substantially longer, healthier life

Saw something interesting mentioned today on ABC with human trials intended in a few months.

DNA repair discovery could lead to drugs to reverse ageing, fight cancer and help space travel

Critical step in DNA repair, cellular aging pinpointed

 

Just my 2c.

My only source here is Michael Mosley and his 5:2 diet book and his series on BBC; Horizon. From memory, what we know is that people who fast or have calorie restricted diets produce less IGF (Insulin Growth Factor) which is associated with less cancer and cell damage in a person's body. The theory is your body spends less time replicating and creating new cells and more time repairing what it has.

 

Actually for anyone who has ever looked at the 5:2 diet and it's overall benefits to your health.. this looks interesting :

Fasting Mimicking Diet (FMD
http://www.telegraph.co.uk/wellbeing/diet/why-weve-all-been-doing-the-fast-diet-wrong/

In his study, reported this week in the journal Cell Metabolism, old mice placed on cycles of a four-day low-calorie diet had reduced visceral belly fat, and increased numbers of progenitor and stem cells in several organs — including the brain, where neural regeneration was boosted, as was memory."

"...Decreasing meal frequency is pretty painless and by reducing meal frequency we naturally reduce inflammation (the hallmark of modern chronic disease) in our bodies.’’

 

There link to a talk earlier in this thread, about the interaction between metabolism, diet and cancer. Well worth listening to.

Another study in last week's Science update suggests pancreatic function is improved by fasting...


http://science.sciencemag.org/conte...ci_2017-03-23&et_rid=103986717&et_cid=1233308

 

NAD hits the news again...

http://www.abc.net.au/news/2017-08-...prevent-miscarriage-and-birth-defects/8785566

 

There's different forms of Vitamin B3 supplements in the marketplace, including: NR, niacinamide, niacin and inositol hexaniacinate. It's unclear to me which forms is attributable to benefit for which study.

 

My understanding is that they all convert to NAD⁺, which is the key energy carrier and conenzyme for DNA repair, so it shouldn't matter too much which form you take. However, the holder of the NR patent disagrees...

https://seekingalpha.com/article/4040764-chromadex-response-claim-niagen-just-expensive-vitamin-b3

One thing to keep in mind is that Niacin can be toxic at high doses. I don't think this is the case with NR.

More on the Victor Chang Institute and birth defect study here:

http://www.sciencemag.org/news/2017...ly_2017-08-11&et_rid=103986717&et_cid=1487863

Fascinating...

 

http://www.sciencedirect.com/science/article/pii/S1550413116302443

https://www.nature.com/nrm/journal/v17/n11/full/nrm.2016.93.html

 

I've been seeing a lot of mentions of this recently... keeping an eye on it for obvious reasons.

 

More mentions - https://cosmosmagazine.com/biology/time-to-pop-an-anti-ageing-pill

 

Another mouse experiment;

https://www.sciencedaily.com/releases/2018/07/180709111137.htm

 

Me too, hopefully market availably isn't coming too late.

 

You can get it on iHerb

https://www.nature.com/news/to-stay-young-kill-zombie-cells-1.22872
Think some of you may have read this. Worth noting it lists a few senolytic substances (what theyre calling it, that removes senescent cells from tissue and allows them to be replaced with new tissue - seems like a different one for different tissue is needed) for different tissues.

"dasatinib, which eliminates human fat-cell progenitors that have turned senescent; and a plant-derived health-food supplement, quercetin, which targets senescent human endothelial cells, among other cell types. The combination of the two — which work better together than apart — alleviates a range of age-related disorders in mice"


https://www.nejm.org/doi/10.1056/NEJMoa1515319
http://agencia.fapesp.br/male-hormone-reverses-cell-aging-in-clinical-trial/23558/
Danazol is interesting, because it was previously tested and shown to increase telomere length, even in subjects with an advanced rate of telomere shortening. Nandrolone was also being looked into for this effect, and the theory goes that anabolic steroids may increase telomere length.


https://www.sciencedirect.com/science/article/pii/S1226845318301131?via=ihub
Another study, a particular compound extracted from ginseng (you wont know how much or even if theres enough in simple ginseng) may also help remove senescent cells from skeletal muscle.


Multi-faceted approach would likely be best, there is another important drug called trodusquemine. It was being tested for breast cancer and past human safety trials which is great, as other studies on the drug in animal testing showed that a single dose reverses atherosceloris, ie removes plaque, and also fatty deposits, I forget which, but it was tested in two animals very far apart on the evolutionary tree, so likely chances are that it can do the same in humans. Additionally, it is apparently able to treat parkinsons disease, as it can do what squalmine does in that regard, but actually able to cross the blood brain barrier.

oddly enough heres an article showing parkinsons is associated with senescent cells.. https://www.nextbigfuture.com/2018/08/senescent-cells-associated-with-alzheimers-disease.html

"The drugs are dasatinib, a chemotherapy medication that is U.S. Food and Drug Administration-approved to treat leukemia, and quercetin...After three months of treatment, the findings were exciting. “The mice were 20 months old and had advanced brain disease when we started the therapy,” Dr. Orr said. “After clearing the senescent cells, we saw improvements in brain structure and function."


This site is worth following
https://www.nextbigfuture.com/tag/antiaging



https://www.sciencedaily.com/releases/2017/03/170316151703.htm
"The drug has two advantages that are expected to smooth the path to the clinic. First, MSI-1436 stimulates tissue regeneration in zebrafish and mice, which are separated by approximately 450 million years of evolution. This increases the likelihood it will work in humans too"

"The original research on MSI-1436 was conducted by Yin in zebrafish, an organism that can regenerate the form and function of almost any body part. He found that the administration of MSI-1436 increased appendage regeneration by 200 to 300 percent. Follow-up research showed that MSI-1436 also stimulated zebrafish heart regeneration to the same degree."

"Yin followed the studies in zebrafish with studies in adult mice, which, like humans, have a limited capacity for regeneration. "

https://www.ncbi.nlm.nih.gov/pubmed/25623533
Claramine could be a more easily made alternative to trodusquemine in at least some respects, Id like to see studies on atheroscelorosis and regeneration done on that.

 

Nicotinamide Riboside is now on sale in NZ as a supplement called True Niagen

 

Another senolytic substance - Fisetin. Large amounts of it in strawberries.

https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

Not sure on dosage needed in terms of kg's of strawberries

Edit: a bit more googling...

• 'The usual approach to scale up estimated doses from mouse studies to initial human trials leads to 500 mg per day for five days for a 60kg human.' - https://www.fightaging.org/archives...tin-to-be-a-surprisingly-effective-senolytic/
• 'A Japanese study reported that the highest concentration of fisetin was found in strawberries (160 μg/g, or microgram/gram) followed by apple (26.9 μg/g) and persimmon (10.5 μg/g)' - https://articles.mercola.com/sites/...24/strawberry-fisetin-key-to-good-memory.aspx
• and those two numbers leads to around 3.2kg per day for 5 days...

Interesting to think of though... if you were averaging a kilo of fruit and vege every day. Sure you are not close to the 500mg/day needed for a 5 day protocol, but the consumption of such a volume day in and day out would be surely beneficial in senolytic outcomes. Especially since you would getting multiple senolytic substances.

The verdict is not in yet if fasting is senolytic from my quick google and read.

 

Given that the yield via digestion is not very efficient, would it be better to extract the substance and make it into an injectable form?

 

No clue - in the comments on the second link folks are reporting they are consuming Fisetin pills. This is very early days, so protocols are yet to be established.

 

Nice discussion with aussie expert David Sinclair on this stuff here

https://peterattiamd.com/davidsinclair/

 

Just on urolithin A;

https://www.businesswire.com/news/h...ntis-SA-Announces-Completion-Series-Financing

Slowly stuff is getting their t's crossed and their i's dotted.

 

Joe Rogan interviews David Sinclair