10 replies to this topic

[Heisenburger]

I’m part way through de Grey’s second book, and I’ve decided to embark on a plan to do as much for my mitochondria as is currently possible. It seems like a logical game plan—since Alagebrium has turned out to be a dead end and there’s pretty much nothing we can do about AGEs right now, I figured I’ll focus my attention on mitochondrial damage and sirtuin-activating compounds until such a time as we can figure out how to cleave glucosepane crosslinks. So I’ve assembled the following arsenal, a lot of which I’ve already been taking: C60, PQQ, MitoQ, methylene blue, resveratrol, Niagen, pterostilbene, and fisetin. The last four I’m obtaining from this supplement, and the first four are each taken as separate compounds. Is it best to take these on an empty stomach? I’ve read (partially here) that it is best, but I thought I would run it past the LongeCity brain trust and see what the consensus is. Also, is there anything significantly glaring that I’m missing? Is there anything I should add?

[niner]

It's kind of annoying that LEF only gives you 0.5 mg pterostilbene.  That sounds like they're just putting in a wee bit so they can put the name on the label.   Generally speaking, an empty stomach is better for most of these.  It doesn't matter for c60oo; I always take that with food.  In fact, I take in on food.  I use it just like olive oil.  Things to add... Pterostilbene?  Elysium Basis has 50 mg/serving, to give you an idea of an effective dose.

[Heisenburger]

It's kind of annoying that LEF only gives you 0.5 mg pterostilbene.

 

Yeah, I know—it’s like when they added two milligrams of Niagen to 14 capsules of LEF Mix. It was almost laughable. Do they think we’re brain-damaged or something? If you look closely at the label though, it lists a full-spectrum red grape extract which also contains pterostilbene, so I’m going to e-mail them and ask them how much it adds up to altogether. If it’s not a lot, then I’ll switch tracks and obtain the compounds separately. Aside from LEF Mix, I never buy formulations, but I made an exception in this case just for convenience’s sake, and because the wiki article on fisetin piqued my interest.

[sthira]

Jarrow's pterostilbene is only $13 a bottle for 60 50mg pills. What's up with the methylene blue? I realize there are long threads about it -- some of which I've read -- but I didn't really discover what people derive from it. What do you see in it?

[aribadabar]

 

It's kind of annoying that LEF only gives you 0.5 mg pterostilbene.

 

Yeah, I know—it’s like when they added two milligrams of Niagen to 14 capsules of LEF Mix. It was almost laughable. Do they think we’re brain-damaged or something? If you look closely at the label though, it lists a full-spectrum red grape extract which also contains pterostilbene, so I’m going to e-mail them and ask them how much it adds up to altogether. If it’s not a lot, then I’ll switch tracks and obtain the compounds separately. Aside from LEF Mix, I never buy formulations, but I made an exception in this case just for convenience’s sake, and because the wiki article on fisetin piqued my interest.

 

 

Fisetin is also underdosed in that LEF formulation. Anything sub 100mg/d is wasting your time. For effective Niagen (and fisetin) supplementation you need to take several tabs of this LEF stuff.

 

I would opt for more highly concentrated individual products.

[Logic]

Heisenburger:
"...since Alagebrium has turned out to be a dead end and there’s pretty much nothing we can do about AGEs right now..."
 
Are we sure about that?
 

Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

...The original AGE breaker...alagebrium (ALT)-711...and recently described pyridinium analogs TRC4186 and TRC4149 ... were designed to cleave AGE cross-links in tissue proteins. As support for their mechanism of action, these compounds 1) released AGE albumin from preformed AGE-albumin-collagen complexes, 2) released immunoglobulins bound to red cells of diabetic rats, and 3) reversed or decreased collagen cross-linking in diabetic rats. Despite these observations, not a single AGE cross-link structure identified in tissue proteins to date...contains a dicarbonyl structure susceptible to the proposed mechanism of action of AGE breakers. Indeed, the proposed target of AGE breakers, dicarbonyl cross-links, would be reactive carbonyl compounds, which are unlikely to accumulate in protein... 

 

...Despite the lack of evidence for their AGE-breaking activity, AGE breakers are potent chelators, and their hydrolysis products have even stronger chelating activity than the intact compounds (23) (Table 1)...

 

...Administration of triethylenetetramine for 6 months caused a significant ∼5% reversion of left ventricular mass toward normal...

http://www.ncbi.nlm....les/PMC3282805/

Perhaps the the much sought after AGE breaking solution has been right under our noses in the form of a combination of chelation therapies selected to simultaneously/synergistically? 'attack' the different types of AGEs?
 
I note that the Major Mouse Testing program plans to test age breakers...
http://www.majormouse.org/?q=node/57
 
 
I would add Chebulic Acid to the combinations of chelators tried:
 

Effects of Chebulic Acid on Advanced Glycation Endproducts-induced Collagen Cross-links
...Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50 = 1.46 ± 0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50 = 72.2 ± 2.4 mM).

https://www.jstage.j...-00034/_article

 

Suppression of the onset and progression of collagen-induced arthritis by chebulagic acid screened from a natural product library.
...all clinical scores, serum levels of total and anticollagen IgG, and levels of interleukin-10 (IL-10) and IL-6 were reduced, while serum levels of transforming growth factor beta (TGFbeta) were markedly elevated. The number of granulocytes was reduced, but the proportion of CD4+,CD25+ T cells was greater in the knee joints of CHE-treated CIA mice. Expression of Foxp3 and TGFbeta messenger RNA was also augmented significantly in the knee joints of CHE-treated CIA mice in the therapeutic dosing model.

http://www.ncbi.nlm....pubmed/15641090
 

NB:
I assume the above study is referring to TGF-β3 and not TGF-β1 & TGF-β2 which you DON'T want elevated!

 

The other cause of increased TGF-β1 & 2 and TNF-α and (bad) NF-kB (= less telomerase = epigenetically older phenotype), is low level, chronic infection.
DRACO looks very promising, but Bavituximab is much closer to production.
Solutions available right now are ...  

 

 

Edited by Logic, 28 January 2016 - 07:24 PM.

[Heisenburger]

I dunno…but I’m never sure of anything, especially when it comes to biology or biochemistry. it’s gonna take me a while to chew through these papers, but my immediate (albeit knee-jerk) reaction is “if this were for real, I would already know about it.” The good thing however, is that if it is for real, we won’t have to wait half a century for primate test results to demonstrate its efficacy. At the very least, you shined a little beacon of hope in my direction. I wasn’t willing to just yet resign myself to going gently into that good night the same way my parents did, both of whom passed away at the age of 77 from cardiovascular disease. I don’t give a fat rat’s ass about my skin right now; I want something that will reverse stiffening of the cardiovascular system. I’ll fret about looking like Yoda in about 30 years when I’m in my eighties. Although if it turns out that the treatment will rejuvenate the integumentary system, it will be a nice little bonus that you certainly won’t hear me or anybody else complaining about.

[Logic]

Look  at these GoogleSiteSearch results and compare the results of chelation therapy to those one would expect from AGE clearance.

 

https://cse.google.c...cular chelation

 

Here is one I started 3 years ago:

http://www.longecity...rapy-with-edta/

 

IMHO this forum should be all over chelation and AGE breaking/blocking.  Especially as the money seems to be going out of its way to dissuade all research.  That's always a big flashing 'look here!' sign for me.  

 

Melatonin and Milk Thistle have been 'banned' here...  (South Africa)

[Nick Kyz]

Well if you want to support mitochondria there's a great compilation here:

http://forums.phoeni...learance.13464/

Edited by Nick Kyz, 03 February 2016 - 04:35 AM.

[Turnbuckle]

Other important mito supplements: Acetyl-L-carnitine and lipoic acid, and minerals important for enzymes of the Krebs cycle, the most important being magnesium, manganese, molybdenum, and zinc. There are others, such as iron and copper, though more is not better when it comes to minerals. There's a Goldilocks range. Several manufactures sell multi-mineral tablets designed for Krebs support.

 

A few others supplements--

 

The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-α-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100.

 

http://www.ncbi.nlm....pubmed/21507065

 

 

Then there's the olive oil phenol hydroxytyrosol--Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes. (Hydroxytyrosol is also a breakdown product of dopamine.)

 

In addition to biogenesis, one needs to get rid of defective mitochondria, so supplements that promote mitophagy--eliminating dysfunctional mitochondria--will be useful. Lithium is an example that is also associated with longer life.

 

Taken together, these findings indicate that long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species.

 

 

Edited by Turnbuckle, 04 April 2016 - 12:19 PM.

[Logic]

Then there's the olive oil phenol hydroxytyrosol--Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes. (Hydroxytyrosol is also a breakdown product of dopamine.)

 

In addition to biogenesis, one needs to get rid of defective mitochondria, so supplements that promote mitophagy--eliminating dysfunctional mitochondria--will be useful. Lithium is an example that is also associated with longer life.

 

More hydroxytyrosol info:

http://www.longecity...nol-hypothesis/

 

More useful info on Lithium, IP3, circadian rhythms and autophagy:

Lithium induces autophagy in an mTOR-independent manner.
But it also activates mTOR.
This mTOR activation partially inhibits the autophagy-inducing effects of lithium.

http://www.longecity...ndpost&p=764699

 

Then there's Niltinib that upregulates PARKIN to the point of:

• Clearing toxic, misfolded proteins  from cells.
• Preventing amyloid secretion into the extracellular space between neurons.
• Facilitating the mitophagy of old, sickly mitochondria.

http://www.longecity...1-month-supply/

 

The clearing of senescent cells:
http://www.longecity...nds-healthspan/