471 replies to this topic

[Bryan_S]

NOVEL THERAPIES: ACTIVATION OF BIOGENESIS http://www.mrc-mbu.c...tion-biogenesis

 

Further reading:

http://www.mrc-mbu.c...ondrial-disease

 

http://www.cell.com/...4131(14)00164-8

[Bryan_S]

Mitochondria | Circulation Research Image Gallery | Page 4

 

Overview of Pyridine Nucleotides Review Series On - Aging, Metabolism, Mitochondria

http://circresearch....hondria/page/4/

 

This appeared on my Nicotinamide Riboside search a few days ago and belongs to a series on mitochondria. It is part of the Circulation Research Image Gallery. No doubt many of you will find a lot of reading here. Circulation Research is an official journal of the American Heart Association and is the official journal of the Basic Cardiovascular Sciences Council of the American Heart Association. Google just recently scanned these pages and I do not have an exact publication date but it is linked into a 2012 study which may have proceeded it http://circres.ahajo.../111/5/604.full

 

http://circresearch....hondria/page/1/

 

http://circresearch....hondria/page/2/

 

http://circresearch....hondria/page/3/

 

Edited by Bryan_S, 26 June 2015 - 05:48 AM.

[Asor]

NOVEL THERAPIES: ACTIVATION OF BIOGENESIS http://www.mrc-mbu.c...tion-biogenesis

Further reading:

http://www.mrc-mbu.c...ondrial-disease

 

http://www.cell.com/...4131(14)00164-8

 

 

One of the authors, Lamperti C, is my doctor.

 

She told me AICAR (which is already used for diabetes treatments) resulted to be toxic to be used in dosages useful for mitochondrial diseases
 

[Bryan_S]

 

NOVEL THERAPIES: ACTIVATION OF BIOGENESIS http://www.mrc-mbu.c...tion-biogenesis

Further reading:

http://www.mrc-mbu.c...ondrial-disease

 

http://www.cell.com/...4131(14)00164-8

 

 

One of the authors, Lamperti C, is my doctor.

 

She told me AICAR (which is already used for diabetes treatments) resulted to be toxic to be used in dosages useful for mitochondrial diseases
 

 

 

Asor, I was thinking of you when I posted this. 

[wbray123]

I am taking nicotinamide, twice daily. Is it the same as nicotinamide riboside? I guess this is a dumb question, but there are son many different names for some of these vitamins. And should I switch? Am mainly interedsted in overall health and ant-aging effects. Thanks.

[BigLabRat]

I am taking nicotinamide, twice daily. Is it the same as nicotinamide riboside? I guess this is a dumb question, but there are son many different names for some of these vitamins. And should I switch? Am mainly interedsted in overall health and ant-aging effects. Thanks.

 
Nicotinamide (NAM) is a component of the nicotinamide riboside (NR) molecule, but it is not the same. They enter the NAD+ production cycle at different points. NR has received a great deal of attention as a way to raise NAD (which seems to have anti-aging effects).

NR and Niacin (Nicotinic Acid, Na) have both been shown to raise NAD significantly.

NAM has not been shown to raise baseline NAD, although it is a clear precursor. To do so it must be transformed via an enzyme called NAMPT, which is not always in plentiful supply. If you want to stick with NAM (NAM and Na are both cheap, unlike NR), you may want to look into ways to raise NAMPT. These include exercise, fasting, caloric restriction, and various other strategies. So it may be possible to get major baseline increases in NAD from NAM, but it probably requires more than just taking NAM alone.

I hope Bryan S will throw in his two cents here, as he is a NAM fan for an assortment of reasons.

[Bryan_S]

 

I hope Bryan S will throw in his two cents here, as he is a NAM fan for an assortment of reasons.

 

 

I can't take Niacin at the dosages I currently maintain in my NAD boosting regiment because of an inflammatory skin condition. There is much to read on this topic overall but its best to mention the darker side of Niacin up front and get past this hurdle see Hepatotoxicity as a side effect of niacin. This is possibly related to metabolism via amidation resulting in NAD production. Although this risk is likely low at under 3 grams per day. Personally you'd have to put me in a straight jacket just to keep me from ripping my skin off from the intense itching.

 

Nicotinamide aka Niacinamide (Nam) is cheap and produces no flush. It should be mentioned that it has been vilified in recent years as a sirtuin inhibitor in tests performed with cells outside their normal biological context, (test tube experiments.) However multiple studies on whole organisms have not produced the same results and it acts as a sirtuin activator and has yielded a host of cellular benefits.

 

Some of you have read the blog by Dr. Vince Giuliano. Here is the source of some of the controversy and mind you he puts Niacin and Niacinamide in a similar light. See Personal note on my affair with niacin to see the root of his bias.  In fact this doctor is very well read by many of us on this thread and his posts are richly detailed. This guy was a Niacin megadose advocate but once your son gets an inflamed liver and has to be hospitalized you're bound to change your tune.

 

Like many of you I can only afford to supplement with so much NR. Don't get me wrong, if I could afford to take 3 grams per day of Nicotinamide Riboside I likely would. I do not think the nicotinamide riboside kinase 1 and 2 salvage paths are as rate limited as the nicotinamide phosphoribosyltransferase NAMPT salvage pathway. In addition I also take Pterostilbene and Honokiol as Sirt1 and Sirt3 activators and I load up on the separate NAD precursors at opposite ends of the day. 

 

So here are 3 readily available NAD precursors. All 3 are collectively known as Vitamin B3 but each NAD precursor takes a different path into the cell. These paths produce different effects but they also share many common benefits as well. That's my 2 cents worth.

Edited by Bryan_S, 27 June 2015 - 07:00 AM.

[Bryan_S]

NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

 

http://www.cell.com/...4131(15)00266-1

 

If someone has access to the full text this looks like a good read to post here. 

[malbecman]

NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus

 

http://www.cell.com/...4131(15)00266-1

 

If someone has access to the full text this looks like a good read to post here. 

 

 

I have it but the max file size on the file uploader is 2MB and it's ~2.5MB.   Any suggestions?

 Maybe try this link to Google drive....

 

https://drive.google...iew?usp=sharing

[Marty D]

Interesting reading. Thanks for hosting the article. A couple of quick observations:

 

"Also, as discussed in Food Sources and Bioavailability of NAD+ evidence suggests that NA might be quickly metabolized to NAM in the gut and the liver (Collins and Chaykin, 1972)."

 

This was discussed early on in the forum after the NR findings were announced. And:

 

"The presence of significant NR levels in blood after oral intake is, however, not apparent, as classic reports generally indicate that radiolabelled NR is transformed into NAM at the brush border (Gross and Henderson, 1983)."

 

Above has also been mentioned before. Hmm.

[Bryan_S]

I have it but the max file size on the file uploader is 2MB and it's ~2.5MB.   Any suggestions?

 Maybe try this link to Google drive....

 

https://drive.google...iew?usp=sharing

 

 

Worked fine, it's one of the most complete papers I've seen pulling the most relevant & "recent" studies together.

 

"Excessive DNA damage dramatically reduces NAD+ levels (Berger, 1985), even down to 20%–30% of their normal levels (Houtkooper et al., 2010a). In fact, the enzymatic properties of PARP1 indicate that it is an avid NAD+ consumer, with NAD+ increasing up to 2-fold in Parp1-KO mouse tissues" I've been recently following PARP's research and many feel their competition for NAD+ pool is enormous. They aren't the only consumers of NAD+ but as levels drop with age a cell eventually reaches the breaking point.

 

THANKS

[malbecman]

 My pleasure....at least part of it was US Federally funded (National Institutes of Health (R01AG043930) ) so we certainly have a right to read it.

[APBT]

I thought this had been posted but, a quick search didn't reveal it, so.....USE OF NICOTINAMIDE RIBOSIDE TO TREAT HEARING LOSS patent application

[wbray123]

Thanks for the responses to my question. I am not very knowledgeable about the technical aspects of all this.I have no scientific or medical background other than popular articles designed for lay people. I take a multivitamin loaded up with lots of B vitamins. If I start Nicotinamide Riboside would there be any benefit to continuing with the additional Nicotinamide? Should I stop that or be concerned about overloading on it? Thanks again for being willing to explain things to me.

[Asor]

Thanks for the responses to my question. I am not very knowledgeable about the technical aspects of all this.I have no scientific or medical background other than popular articles designed for lay people. I take a multivitamin loaded up with lots of B vitamins. If I start Nicotinamide Riboside would there be any benefit to continuing with the additional Nicotinamide? Should I stop that or be concerned about overloading on it? Thanks again for being willing to explain things to me.

 

Impossible to answer because there arent any studies about Nicotinamide Riboside toxicity at higher doses, especialy on humans, they are just being performed in this time and will be available soon.

But i think the suggested dosage of 250mg/day should be safe.

And beside that, you are never sure. Just look up the SELECT study on Vitamin E and prostate cancer... at first it was thought supplementing with Vitamin E was a good idea, they did this huge study called SELECT, one of the biggest study in history about preventive medicine for cancer, and it turned out Vitamin E increased the possibilities of getting prostate cancer by a good percentage.

[timbur]

<snip>

 

Like many of you I can only afford to supplement with so much NR. Don't get me wrong, if I could afford to take 3 grams per day of Nicotinamide Riboside I likely would. I do not think the nicotinamide riboside kinase 1 and 2 salvage paths are as rate limited as the nicotinamide phosphoribosyltransferase NAMPT salvage pathway. In addition I also take Pterostilbene and Honokiol as Sirt1 and Sirt3 activators and I load up on the separate NAD precursors at opposite ends of the day. 

 

So here are 3 readily available NAD precursors. All 3 are collectively known as Vitamin B3 but each NAD precursor takes a different path into the cell. These paths produce different effects but they also share many common benefits as well. That's my 2 cents worth.

 

 

I probably am just being dense today.  Would the "3 readily available NAD precursors" you take be Niacin, NAM, and (of course) NR?

 

In the "Other Precursors" thread, you had mentioned some others, but I imagine those are not readily available.  (Post: http://www.longecity...-5#entry701424)

 

The advice I've seen on Niagen's NR is to take it in the morning, which is what I am doing (2x250mg).  But you "load up on the separate NAD precursors at opposite ends of the day".  This is the first time I can recall seeing someone advise this.  You have no ill effects, for instance with sleeping, I presume.

 

I've not looked into Honokiol before.  I will have to look into it.  Lots of companies are selling magnolia bark extract, which is the source for honokiol.  If you have particular advice on it, or a good forum thread on it, please reply or PM me with info.

 

Thanks so much for all your contributions on this topic in this thread and others.

[Bryan_S]

 

<snip>

 

Like many of you I can only afford to supplement with so much NR. Don't get me wrong, if I could afford to take 3 grams per day of Nicotinamide Riboside I likely would. I do not think the nicotinamide riboside kinase 1 and 2 salvage paths are as rate limited as the nicotinamide phosphoribosyltransferase NAMPT salvage pathway. In addition I also take Pterostilbene and Honokiol as Sirt1 and Sirt3 activators and I load up on the separate NAD precursors at opposite ends of the day. 

 

So here are 3 readily available NAD precursors. All 3 are collectively known as Vitamin B3 but each NAD precursor takes a different path into the cell. These paths produce different effects but they also share many common benefits as well. That's my 2 cents worth.

 

 

I probably am just being dense today.  Would the "3 readily available NAD precursors" you take be Niacin, NAM, and (of course) NR?

 

In the "Other Precursors" thread, you had mentioned some others, but I imagine those are not readily available.  (Post: http://www.longecity...-5#entry701424)

 

The advice I've seen on Niagen's NR is to take it in the morning, which is what I am doing (2x250mg).  But you "load up on the separate NAD precursors at opposite ends of the day".  This is the first time I can recall seeing someone advise this.  You have no ill effects, for instance with sleeping, I presume.

 

I've not looked into Honokiol before.  I will have to look into it.  Lots of companies are selling magnolia bark extract, which is the source for honokiol.  If you have particular advice on it, or a good forum thread on it, please reply or PM me with info.

 

Thanks so much for all your contributions on this topic in this thread and others.

 

 

I'm having trouble posting links and have contacted the administrators to solve this problem.

 

I'm not making advice to others, the research doesn't yet go far enough to support the path I've taken. The nicotinamide riboside kinase 1 and 2 salvage paths are separate from the nicotinamide phosphoribosyltransferase NAMPT salvage pathway which niacinamide takes. We now accept that each path is separate from the other and each path has its own separate inhibitors to limit (NMN) production. Each of these 2 paths produce nicotinamide mononucleotide (NMN) so here is a convergence of each pathway at this one point. I'm hitting each one of these 2 paths separately once per day in hopes of slowly increasing their overall capacity so as to not over saturate and block either path. So I see hurdles to overcome from inhibitors along each pathway and once we invoke these inhibitors it takes time to clear the system for another round. Its my belief we need to create demand to increase capacity. Along those lines I also exercise to help increase the NAMPT salvage pathway. 

 

In the end Nicotinamide mononucleotide also has its own NMNAT inhibitor so this becomes the final hurdle.

 

I mentioned 3 readily available "oral" NAD precursors and Niacin in one of them and could also be used but it wouldn't be tolerable, at least for me. We could also acknowledge several others that might be effective when taken by injection however the cell membrane levels the playing field anyway. For instance lets say we could order nicotinamide mononucleotide (NMN) which is an expensive proposition. Question; Would we gain anything by taking it? We could take it orally but it would break down into mostly niacinamide in the gut. And say some of it was passed and absorbed unaltered or we injected it in the first place, the cell membrane would enzymatically cleve it into NR anyway before its absorption thru the cell membrane. We could also start with NAD or NADH which is available but again we would run into a similar problem with our digestive system. Again we could inject it but as we've seen in research concerning eNAD the cell membrane breaks it down into its precursors before its absorbed, so what's the point?

 

What seems to be more and more apparent is the NAD+ and NADH ratio will put the breaks on NAD synthesis at a certain point anyway. However it appears the amount of NAMPT or nicotinamide riboside kinase 1 and 2 production can increase over time and build more peak throughput capacity. If this idea holds true a larger cellular pool of (NMN) can be made readily available in the wings and that's the best I can hope for.

 

As far as sleep niacinamide mellows me out anyway and I cap my total B3 consumption at 3 grams per/day between the precursors. My doctor also runs a liver panel for me.  

 

For me since I have both inflammatory joint issues and inflammatory skin issues I have a "Canary in the coal mine" and get feedback pretty fast. I've tried some things that haven't worked and for now this is. So until the PK data becomes available on NR dosages and we see some studies supporting the use of more than one NAD precursor, its all guess work at this point and I'm not making any advice to others but this is what I'm doing for what its worth.

Edited by Bryan_S, 03 July 2015 - 09:10 AM.

[Bryan_S]

Sirtuins and the Metabolic Hurdles in Cancer

Volume 25, Issue 13, pR569–R583, 29 June 2015

Natalie J. Germanemail, Marcia C. Haigisemail

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA

DOI: http://dx.doi.org/10...cub.2015.05.012

  http://www.cell.com/...9822(15)00556-4  

 

Sirtuins and NAD+ Sensitivity

"Sirtuins are unique sensors of the metabolic state because their NAD+-dependent enzymatic activity intrinsically couples their function to the metabolic status of the cell or organism [37, 38, 39, 40, 41]. According to the metabolic state of the cell, the ratio of NAD toggles between varying amounts of NAD+ and NADH [42]: NADH is a high-energy, reduced form of NAD that can donate electrons to the electron transport chain, and NAD+ is the lower energy, oxidized counterpart required to fuel glycolysis. When the cell uses oxidative metabolism, NADH generated by the TCA cycle and glycolysis donates electrons to complex I of the electron transport chain (ETC). This contributes to a proton gradient that will ultimately produce ATP. Upon electron transfer, NADH is oxidized back to NAD+. In highly glycolytic cells with low ETC function, NAD+ is alternatively regenerated from NADH via lactate dehydrogenase (LDH) activity in order to sustain glycolysis. NAD+ can also be synthesized de novo from tryptophan and vitamin B3 derivatives, or via salvage pathways using nicotinamide or nicotinamide riboside. Thus, the NAD+:NADH ratio is affected by the cellular metabolic state, and changes in this ratio have potential to impact sirtuin enzymatic activity.

 

Several studies have linked sirtuin activity with the organismal metabolic status and cellular NAD ratio. In many tissues, the NAD+:NADH ratio is low during nutrient excess and high during nutrient deprivation [43, 44]. For example, in skeletal muscle and white adipose, the NAD+:NADH ratio is elevated during calorie restriction [45]. Due to their dependency on NAD, it is not surprising that certain sirtuins are reported to have increased activity in response to high NAD+levels [46]. For example, SIRT1 in skeletal muscle and brain is activated by exercise, fasting and calorie restriction [47, 48, 49]. In contrast, low NAD+ levels are observed with obesity as well as old age, two factors that confer increased risk for many cancers and are also linked to decreased sirtuin activity [50, 51]. Along these lines, growing evidence suggests that loss of sirtuin function plays a role in obesity- and age-associated cancers [8, 52].

 

It is proposed that there are tissue-type and cellular-compartmentalization variations in NAD+ and NADH levels that may lead to distinct alterations of sirtuin activity in different contexts [42]. NAD+ is generated by biosynthetic reactions in the mitochondria, nucleus and cytosol [53]. Generally NAD+ is most abundant in mitochondria, particularly in highly metabolically active tissues, such as cardiac myocytes, although the distribution varies across cell types [54]. Nuclear NAD+can be depleted upon DNA damage when this molecule is used as a substrate for the poly(ADP-ribose) polymerase (PARP) family of enzymes to activate DNA repair pathways [55]. Inhibiting PARPs elevates NAD+ levels, presumably in the nucleus, and accordingly was shown to boost activity of nuclear SIRT1 and not mitochondrial SIRT3 [56]. Upon PARP activation, the mitochondrial permeability transition pore opens to allow flow of NAD+ from mitochondria to the cytosol and nucleus in order to allow further PARP function. Work by Yang et al. [38]suggests that upregulation of NAD+ biosynthesis enables mitochondrial NAD+ to be maintained at physiological levels even though cytosolic and nuclear NAD+pools are depleted upon genotoxic stress. Promotion of NAD+ biosynthesis in the mitochondria was further indicated to be dependent on SIRT3 and SIRT4 [38]. It will be useful for future studies to validate these NAD+ measurements in live cells in order to avoid the reliance on subcellular fractionation."

 

[Bryan_S]

SIRT1 and SIRT2: emerging targets in neurodegeneration

Gizem Donmez1*, Tiago F. Outeiro2**

Keywords: aging; Alzheimer’s disease; neurodegeneration; Parkinson’s disease; sirtuins

Full-text Available from: Tiago Fleming Outeiro, Jul 05, 2015

 

http://www.researchg...bc5d000000.pdf?

Edited by Bryan_S, 05 July 2015 - 09:06 PM.

[Bryan_S]

Cancer as a mitochondrial metabolic disease

 

Thomas N. Seyfried* Biology Department, Boston College, Chestnut Hill, MA, USA

 

http://journal.front...2015.00043/full

 

Since mitochondrial health goes hand in hand with NAD and mitochondrial oxidative phosphorylation I would be remiss if I didn't post this article. I found the Summary of Nuclear-cytoplasmic Transfer Experiments to be particularly interesting.

 

 

Mitochondria control oncogenesis through metabolic reprogramming by John Hewitt report

http://medicalxpress...rogramming.html

 

Mitochondria. Credit: Wikipedia commons

 

Edited by Bryan_S, 10 July 2015 - 03:56 PM.

[Bryan_S]

• Nicotinamide-Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults. This study will determine whether Nicotinamide Riboside (NR), a naturally occurring compound that is similar to vitamin B3 and found in milk, yeast, and other food products, improves body functions including blood vessel, physical and brain functions in older adults. Study participants will take both NR and placebo supplements for 6 weeks each in a randomly determined order. Measurements will be made at the end of each intervention period. If you are interested in participating in this study, please call 303-735-4799 or email cvstudy@colorado.edu.

http://www.colorado....volunteers.html

 

http://investors.chr...rol-newsarticle

 

http://spot.colorado.edu/~chma3573/

[Bryan_S]

PhD Fellow: The importance of nicotinamide adenine dinucleotide (NAD) metabolism of insulin sensitivity and substrate selection in human skeletal muscle during metabolic stress

http://www.jobzonen....abolisk-stress/

 

Business

NNF Center for Basic Metabolic Research

Workplace

Copenhagen N

Created

July 18, 2015

Expires

August 2, 2015

Job category

Education

Branch

Other

Time

Full time

 

 

•  

Faculty of Health Sciences, University of Copenhagen

The Novo Nordisk Foundation Center for Basic Metabolic Research

 

The importance of nicotinamide adenine dinucleotide (NAD) metabolism of insulin sensitivity and substrate selection in human skeletal muscle during metabolic stress

 

 

A 3-year PhD scholarship is available for occupation by the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Health Sciences, University of Copenhagen per. September 1, 2015 or as soon as possible thereafter. The scholarship includes a study of the importance of NAD metabolism in human skeletal muscle insulin sensitivity and substrate selection during metabolic stress.

 

 

 

About CBMR

At the Faculty of Health Sciences, University of Copenhagen, was The Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) established in autumn 2010 on the basis of a dispensation from the Novo Nordisk Foundation. The center, which has 230 employees and affiliates, consists of five scientific sections, a unit of research communication and a number of satellites abroad. There is also a common transverse administration department. The unemployed Ph.D.Fellow is the section for Integrative Physiology, which is led by scientific director, Professor Juleen Zierath. Main supervisor on the project will be Associate Professor Jonas T. Treebak, and will be conducted in collaboration with Associate Professor Niels Jessen, Aarhus University Hospital. You can read more about CBMR on http://metabol.ku.dk .

 

 

 

Project background

Type 2 diabetes is now a widespread disease, and new alternatives for prevention and treatment of the disease is important to clarify. In this study, we want to investigate the effect of a relatively new found vitamin B3, called Nicotinamide Riboside (NR), and its effect on insulin sensitivity in humans. The purpose of the study is to elucidate the molecular mechanisms underlying the beneficial effects of NO on insulin sensitivity. It is known that NO therapy increases the NAD levels in the cells and in animal studies, this is shown to enhance the activity of the NAD-dependent sirtuins. It is believed that increased sirtuin-mediated deacetylation of transcription factors and proteins involved in mitochondrial ATP synthesis is to increase the oxidation of fat and improve insulin sensitivity. In this study, we want to examine this hypothesis in obese but otherwise healthy subjects, alone and in combination with endurance training. These studies will be the first human studies to elucidate the long-term effects of NO treatment on insulin sensitivity and substrate metabolism.

 

 

 

We are seeking a candidate who

•  
• Is a doctor authorized to independently act
•  
• Have clinical experience in the endocrinology specialty
•  
• Can be based both in Copenhagen and Aarhus for longer periods of time
•  
• Have good understanding of statistical design of experiments and subsequent data processing
•  
• Is analytical and constructive thinking
•  
• Is fluent in spoken and written English
•  
• Is highly motivated and hardworking with strong interpersonal skills
•  
• Is flexible and thrive with a large width compared. Tasks
•  

 

 

Wages and working conditions 

Post will be filled by. September 1, 2015 or soon thereafter. The appointment is three years and is subject to agreement between the AC and the Ministry of Finance regarding salaried PhD students as well as agreement on pay increases for PhD students at the Faculty of Medicine of 5 January 2004. The fellow has obliged - without additional remuneration - to carry out duties in connection with teaching, etc. for up to 840 hours of work during the employment period. There is scope for negotiation of supplements.

 

 

Applications

Apply for the position by pressing "Send Application" below. The application must include: 

•  
• Motivated application
•  
• CV including publication list
•  
• Graduate Certificate
•  
• Possibly. opinions
•  

 

 

The application deadline is 2 August 2015. Any applications received after this date will not be considered. We only accept online applications. For any administrative inquiries please contact Ditte Maria Bohn, email dmbohn@sund.ku.dk. 

 

 

 

Application Procedure

After the application deadline selects the recruitment notified leader, with advice from the appointment committee which applicants are assessed.All applicants will be immediately thereafter notified whether their application has gone on for the assessment of an expert assessment.Selected candidates will be informed of the committee, and each candidate will have the opportunity to comment on the part of the assessment relating to themselves. You can read about the recruitment process at http://jobportal.ku.dk . 

 

 

 

University of Copenhagen wishes to reflect the surrounding community and encourages everyone regardless of personal background to apply for the position.

 

 

[Bryan_S]

First step toward gene therapy treatment of mitochondrial disease unlocked by scientists Gene-based cures for human diseases are now on the horizon Date: July 15, 2015 Source: Oregon Health & Science University Summary: The first critical step in developing novel gene and stem cell therapy treatments for patients with mitochondrial disease has been revealed by scientists. This breakthrough sets the stage for replacing diseased tissue in patients and opens the door to a world of regenerative medicine where doctors are able to treat human diseases that are currently incurable.

 

http://www.sciencedaily.com/releases/2015/07/150715133510.htm

[Bryan_S]

Sometimes combing the blogs give up a few studies long forgotten.

 

Margaret's Corner | LIVING WITH SMOLDERING MYELOMA

Nicotinamide (vit B), IL-1 beta and PARP cleavage

 

Very interesting read on nicotinamide with a number of related studies.

Edited by Bryan_S, 19 July 2015 - 11:49 PM.

[Bryan_S]

NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

 

William T. Harkcoma,1, Ananda K. Ghosha,1, Matthew S. Sungb,1, Alexandre Matovb , Kevin D. Brownc , Paraskevi Giannakakoub , and Samie R. Jaffreya,2 a Department of Pharmacology, b Department of Medicine, and c Department of Otolaryngology–Head and Neck Surgery, Weill Cornell Medical College, Cornell University, New York, NY 10065 Edited* by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved May 8, 2014 (received for review March 6, 2014)

 

Nicotinamide adenine dinucleotide (NAD+) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assembly and disassembly of microtubules is markedly altered by NAD+. Furthermore, we show that the disassembly of microtubule polymers elicited by microtubule depolymerizing agents is blocked by increasing intracellular NAD+ levels. We find that these effects of NAD+ are mediated by the activation of the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents microtubule disassembly and apoptosis elicited by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD+ on microtubule polymers. Taken together, these data demonstrate that NAD+ and SIRT3 regulate microtubule polymerization and the efficacy of antimicrotubule agents.

 

http://www.pnas.org/.../E2443.full.pdf

 

Video

http://www.pnas.org/....DCSupplemental

 

Edited by Bryan_S, 20 July 2015 - 12:15 AM.

[Bryan_S]

Just a slew of results turned up today in the area of mitochondrial remediation tools.

 

The red fluorescent areas in this image of the microscopic worm C. elegans mark free radicals that build up in worms with mitochondrial disease.

 

Novel treatments emerging for human mitochondrial diseases

http://www.scienceda...50720092310.htm

source study "Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease"

http://www.ncbi.nlm....pubmed/26041819

 

 

Vitamin B3 Found to Rescue Mitochondria Defects in Adults with Mitochondrial Myopathy

http://mitochondrial...drial-myopathy/

source study http://onlinelibrary...403943/abstract

 

 

University of Helsinki Researchers Discover Vitamin B3 Form that is Effective in Attenuating Mitochondrial Myopathy Progression

http://mitochondrial...hy-progression/

source study http://embomolmed.em...content/6/6/721

 

Guys this website is http://embomolmed.embopress.org/ is fantastic. You could spend an afternoon browsing these cutting edge articles.

 

 

One article really stood out and sets the preliminary groundwork to a new mitochondrial replacement therapy. The search term "Peptide-Mediated Mitochondrial Delivery" is one we should all start keeping an eye on. Why, with all the talk about future technologies replacing broken Mitochondria here's were progress is happening and since Mitochondria divide to reproduce errors in the mDNA propagate. Even fixing a few Mitochondria at a time could have repletive effects. In fact the new Mitochondria could out compete the defective ones. Here is one technique if adapted to in vivo applications could be the realization of this holy grail.

 

Peptide-Mediated Mitochondrial Delivery for MERRF Treatment Outlined in New Study

http://mitochondrial...d-in-new-study/

 

http://www.sciencedi...465324913005926

http://www.nature.co.../srep07751.html

http://www.ncbi.nlm....pubmed/23006856

 

Edited by Bryan_S, 20 July 2015 - 05:05 PM.

[Bryan_S]

I looked back over the thread and found I'd missed an earlier NR article from March.

 

 

Beyond Resveratrol: The Anti-Aging NAD Fad

By David Stipp | March 11, 2015 |

 

http://blogs.scienti...-aging-nad-fad/

 

http://www.medicalwe...iaging_nad_fad/

[Asor]

thanks for all the mitochondrial related studies Brian_S, i seen most of them but some of this stuff is new even for me and i keep track with google alerts...

 

[Bryan_S]

I think the mitochondrial related studies are at the core of our understanding about aging. Their health seems to be specifically tied to ours, which you more than most people realize. While I'm excited about NAD boosting and NR in particular I realize this is at best only a bandaid to slow the core problem which has eluded scientific investigation. So the question at hand is; "why do our nicotinamide phosphoribosyltransferase (Nampt) levels slowly fall causing our NAD levels to drop?" At some point scientists will focus into the exact problem which everything else seems to cascade from.

 

So Asor while I may be thinking of you when I dig up the mitochondrial related studies, I think they mean a lot to all of us following this topic. Thanks

Edited by Bryan_S, 22 July 2015 - 05:06 PM.

[Bryan_S]

SIRT3 regulates progression and development of diseases of aging

Published Online: June 29, 2015

http://dx.doi.org/10...tem.2015.06.001

 

Highlights

• •Acetylation influences almost every major mitochondrial pathway.
• •Mice lacking SIRT3 develop several diseases of aging at an accelerated rate.
• •SIRT3KO mice might be considered a model of accelerated aging.

The mitochondrial sirtuin SIRT3 is a protein deacylase that influences almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species (ROS) detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response (UPR). Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and, thus, might be a valuable model of accelerated aging. In this review, we discuss functions of SIRT3 in pathways involved in diseases of aging and how the lack of SIRT3 might accelerate the aging process. We also suggest that further studies on SIRT3 will help uncover important new pathways driving the aging process.

 

 

Asor google alerts doesn't always keep up with whats going on. It's keyword based and often you need a number of search terms to generate consistent results. The article above was generated off the search term SIRT3 which we know is associated with mitochondrial biology. Here is another link for you, its one of a number of topic aggregator's, this one is from Cell Press.

http://www.cell.com/...-and-metabolism

 

I'm especially interested in what can be done to keep our SIRT3 active. I previously mentioned Honokiol as a Sirt3 activator and have added this to my regiment. It is a plant polyphenol. There was also a interesting article about it in April. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. As many of us have read there are very few options for treating cardiac hypertrophy and now its believed SIRT3 may play a roll in ameliorating it. Who knew?

 

Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice.

http://www.ncbi.nlm....pubmed/19652361

 

Ancient herbal therapy can prevent -- and reverse -- cardiac hypertrophy in mice

http://www.scienceda...50414125815.htm

 

 

 

The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging

http://www.sciencedi...022282811004706

 

 

Abstract 16685: Honokiol Blocks Cardiac Hypertrophic Response via Activation of SIRT3

http://circ.ahajourn...bstracts/A16685

 

Last but not least

 

Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. http://www.ncbi.nlm....pubmed/25470550

 

So nicotinamide riboside is also a potent activator of SIRT3 and the reason I keep a focus on this and other Sirtuins.

 

The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

http://www.ncbi.nlm....pubmed/22682224

"We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3"

Edited by Bryan_S, 23 July 2015 - 05:42 PM.