2284 replies to this topic

[pamojja]

I'm not the ideal test subject because I take a lot of other supplements, and for some unknown reason, my HbA1c is higher than it should with an average blood glucose in the 80s (mg/dL)  (measured by testing 30 min and 1 hour after each meal plus every 2 hours for 24 hours).

Also my HbA1c does not correlate properly with my blood sugar. (My HbA1c is much higher than it should be for my blood glucose levels)

 

Wow, so you took the effort and tested every 2 hours during 24 hrs? For that you would have to get up from sleep repeatedly! Would you mind sharing a typical 24 hour blood glucose curve?

 

Always wondered how blood glucose behaves during sleep. Since I had an average (9 years of testing) fasting of 101 mg/dl, an avg. 1 hr spike (my highest) at 126 mg/dl, and therefore calculated a mean at 116 mg/dl. Which would give a calculated HbA1c of 5.7%. Actually measured it was 5.1% only. Which calculated back should give a mean BG of 99 mg/dl. Therefore the opposite deviation in my case from yours.

 

Though in my case 0.5% HbA1c deviation could be explained with my high vitamin C intake (study).

[MikeDC]

So even if the majority of NR is broken down to NAM in intestines or liver, if some makes its way to bloodstream and even a little to muscle or other tissue, it can still be effective (Figure 6f).

I'm curious if there is anything we can do to increase the amount of NR that makes it out of the liver, such as combining with other substances.

Fig. 6f doesn't indicate anything about effectiveness, only that some NR made it to the liver without breakdown, even if virtually none of it made it to muscle cells. And what difference does it make if both NAM and NR are converted into NMN and then to NAD+? It all ends up in the same place, so rather than adding yet another supplement to get NR into cells without breakdown (if that were even possible), just supply N+R to begin with.

Nothing in this paper suggest N+R is equal to NR. This N+R thing is just something you made up in your head with no scientific evidence.

[able]

 

 

So even if the majority of NR is broken down to NAM in intestines or liver, if some makes its way to bloodstream and even a little to muscle or other tissue, it can still be effective (Figure 6f).

 

I'm curious if there is anything we can do to increase the amount of NR that makes it out of the liver, such as combining with other substances.

 

 

Fig. 6f doesn't indicate anything about effectiveness, only that some NR made it to the liver without breakdown, even if virtually none of it made it to muscle cells. And what difference does it make if both NAM and NR are converted into NMN and then to NAD+? It all ends up in the same place, so rather than adding yet another supplement to get NR into cells without breakdown (if that were even possible), just supply N+R to begin with.

 

 

 

Sorry, I was a little sloppy in the reference placement.  I meant:

 

So even if the majority of NR is broken down to NAM in intestines or liver (Figure 6f), if some makes its way to bloodstream(Figure 6g)and even a little to muscle or other tissue (Figure 6c,e), it can still be effective.

 

What I mean is, all the precursors raise NAD+ in the liver - some more, some less, but all a LOT more than the NAD+ increase in other tissue.

 

It seems that systemic and liver NAD+ has some benefit, but the muscle tissue drops to 15% without muscle nampt recycling.

 

So systemic NAD+ increase has some limits in its benefit to other tissues. Getting NAD+ to other tissues is more important.

 

Research says the  different precursors increase NAD+ in various tissues differentially.  My thought is that a little NR floating around MIGHT be more effective at increasing NAD+ in muscle.  Or maybe not.

 

But if so, and you can do something to keep the liver from sucking out all the NR (converting to NAD+,NAM, NMR or whatever), and have a little more free-floating NR, it might get more to the other tissues where it is needed such as muscle.

 

Trammel & Brenner hypothesize that once NAD+ reaches a certain point, any remaining NR goes to NAAD, which looks reasonable imo, from the charts.   Perhaps a similar "NAD limit" also allows some excess NR to remain and stay in bloodstream.

 

NAM also elevates NAD and NAAD.  Perhaps NAM with, or before, NR will also reach that limit and allow more NR to "escape" the liver and float around the bloodstream to other tissue.

 

Or perhaps, NR + N + R.  

 

Edited by able, 24 October 2017 - 07:38 PM.

[Turnbuckle]

 

 

 

 

Sorry, I was a little sloppy in the reference placement.  I meant:

 

So even if the majority of NR is broken down to NAM in intestines or liver (Figure 6f), if some makes its way to bloodstream(Figure 6g)and even a little to muscle or other tissue (Figure 6c,e), it can still be effective.

 

What I mean is, all the precursors raise NAD+ in the liver - some more, some less, but all a LOT more than the NAD+ increase in other tissue.

 

It seems that systemic and liver NAD+ has some benefit, but the muscle tissue drops to 15% without muscle nampt recycling.

 

So systemic NAD+ increase has some limits in its benefit to other tissues. 

 

Research says the  different precursors increase NAD+ in various tissues differentially.  I was thinking that a little NR floating around MIGHT be more effective at increasing muscle NAD+ than NAM.  Or maybe not.

 

But if so, and you can do something to keep the liver from sucking out all the NR (converting to NAD+,NAM, NMR or whatever), and have a little more free-floating NR, it might get more to the other tissues where it is needed such as muscle.

 

Trammel & Brenner hypothesize that once NAD+ reaches a certain point, any remaining NR goes to NAAD, which looks reasonable imo, from the charts.   Perhaps a similar "NAD limit" also allows some excess NR to remain and stay in bloodstream.

 

NAM also elevates NAD and NAAD.  Perhaps NAM with, or before, NR will also reach that limit and allow more NR to "escape" the liver and float around the bloodstream to other tissue.

 

Or perhaps, NR + N + R.  

 

 

I still don't see why you want to use NR when NAM is highly elevated in the blood after oral NR (or oral NAM) and easily travels everywhere. Even if NR could be supplied to the body via the blood, it still goes through NMN to get to NAD+ just as NAM does. The whole story about NR is propaganda, and people should realize that. The researchers are selling it and making millions, and their stockholders flit around here like yellow-jackets at a picnic, trying to stop people from realizing that they are being sold a high priced supplement when they could be taking supplements that are 20 times cheaper and more effective.

Edited by Turnbuckle, 24 October 2017 - 07:46 PM.

[able]

 

 

 

 

 

Sorry, I was a little sloppy in the reference placement.  I meant:

 

So even if the majority of NR is broken down to NAM in intestines or liver (Figure 6f), if some makes its way to bloodstream(Figure 6g)and even a little to muscle or other tissue (Figure 6c,e), it can still be effective.

 

What I mean is, all the precursors raise NAD+ in the liver - some more, some less, but all a LOT more than the NAD+ increase in other tissue.

 

It seems that systemic and liver NAD+ has some benefit, but the muscle tissue drops to 15% without muscle nampt recycling.

 

So systemic NAD+ increase has some limits in its benefit to other tissues. 

 

Research says the  different precursors increase NAD+ in various tissues differentially.  I was thinking that a little NR floating around MIGHT be more effective at increasing muscle NAD+ than NAM.  Or maybe not.

 

But if so, and you can do something to keep the liver from sucking out all the NR (converting to NAD+,NAM, NMR or whatever), and have a little more free-floating NR, it might get more to the other tissues where it is needed such as muscle.

 

Trammel & Brenner hypothesize that once NAD+ reaches a certain point, any remaining NR goes to NAAD, which looks reasonable imo, from the charts.   Perhaps a similar "NAD limit" also allows some excess NR to remain and stay in bloodstream.

 

NAM also elevates NAD and NAAD.  Perhaps NAM with, or before, NR will also reach that limit and allow more NR to "escape" the liver and float around the bloodstream to other tissue.

 

Or perhaps, NR + N + R.  

 

 

I still don't see why you want to use NR when NAM is highly elevated in the blood after oral NR (or oral NAM) and easily travels everywhere. Even if NR could be supplied to the body via the blood, it still goes through NMN to get to NAD+ just as NAM does. The whole story about NR is propaganda, and people should realize that. The researchers are selling it and making millions, and their stockholders flit around here like yellow-jackets at a picnic, trying to stop people from realizing that they are being sold a high priced supplement when they could be taking supplements that are 20 times cheaper and more effective.

 

 

I totally agree the Trammell paper misrepresents the data to sell NR.

 

When they say NR is superior to NAM because it raises NAD+ 4 fold vs 2 fold for NAM - looking only at the peak and ignoring the total NAD increase is near equal.

 

And when they say NR is clearly superior to NMN because when added to cells in a test tube, it is faster to enter a cell - totally ignoring that NR does not travel around the bloodstream at detectable levels.

 

Or when they say NR does not increase in liver (as expected), because it is phosphorylated (to NMN) so quickly.  Never mind that NMN also doesn't increase, and NAD+ doesn't until 4 hours later.  Only NAM increases quickly.

 

But, I don't know if NMN does enter cells through some yet unknown pathway, or truly does convert to NR before entering cells. 

 

It may be that a little NR can circulate and make its way into various tissue. 

 

If not, then yes, I'll do whatever I think increases NMN and let that float around to various tissues.

Edited by able, 24 October 2017 - 08:16 PM.

[MikeDC]

NR doesn’t need to go through NAM to get to NR. It doesn’t need NAMPT. It uses NRK1 and NRK2. This is an additional path to NAD+. It bypass the NAMPT rate limiting step.

[MikeDC]

At the end of the day, it is the effect on real humans that counts. Science papers may not be able to tell the whole truth. You can’t deny that hundreds of thousands people are getting fantastic results from NR just in a short period of time. NAM and Niacin has been around a long time. I have not heard people taking NAM claiming getting younger.

[Heisok]

MikeDC this is about the worst comment which I have seen you make.

 

An appeal to the lack of Science for Nicotinimide Riboside, not telling the truth. In fact saying that the Science might not even be able to tell the whole truth. One magical compound indeed !

 

Do you happen to already know that some of these studies are going to be inconclusive? That would really help me.

 

Please leave this thread. You have said your fill. There is plenty here for all of us to figure out the good and bad. Turnbuckle and others, I am sorry for my further hijacking.

[BigLabRat]

You can’t deny that hundreds of thousands people are getting fantastic results from NR just in a short period of time....I have not heard people taking NAM claiming getting younger.

 

But I CAN deny that "hundreds of thousands of people" are taking NR and "getting fantastic results." There isn't data on the results in hundreds of thousands of people. There aren't even hundreds of thousands of people making favorable statements.

 

And I don't care what you have 'heard' about 'claiming getting younger.' (Actually, quite a few people made that claim about niacin in the 50s and 60s. There are whole books on niacin as a miracle nutrient.) A few enthusiastic anecdotes doesn't convince me of anything.

 

I haven't been responding to most of your cherry-picked science, because I'm a scientist (yes, professionally, and, yes, I have a PhD), and I've learned that it's pointless to argue with people who have already made up their minds and don't actually know anything.

 

At this point, nothing is as all that clear in the NAD+ world; we've only scratched the surface, and I try to keep an open mind.

 

But I do wish you'd shut up. Your points are all asinine cheerleading for NR, and you aren't convincing anyone. Much the opposite.

 

 

 

 

[stephen_b]

Regarding fusion, I was reading about how curcumin and sulforaphane synergize to reduce a basket of inflammatory markers (PMID 18841446). I took them both last night (just one pill each), and got a large energy boost and a poor night's sleep. I won't be doing that again. A dose the following morning was great though for energy and a 5 mile run.

 

I wonder if there is any synergistic benefit for fusion from this combo.

[MikeDC]

You can’t deny that hundreds of thousands people are getting fantastic results from NR just in a short period of time....I have not heard people taking NAM claiming getting younger.

But I CAN deny that "hundreds of thousands of people" are taking NR and "getting fantastic results." There isn't data on the results in hundreds of thousands of people. There aren't even hundreds of thousands of people making favorable statements.

And I don't care what you have 'heard' about 'claiming getting younger.' (Actually, quite a few people made that claim about niacin in the 50s and 60s. There are whole books on niacin as a miracle nutrient.) A few enthusiastic anecdotes doesn't convince me of anything.

I haven't been responding to most of your cherry-picked science, because I'm a scientist (yes, professionally, and, yes, I have a PhD), and I've learned that it's pointless to argue with people who have already made up their minds and don't actually know anything.

At this point, nothing is as all that clear in the NAD+ world; we've only scratched the surface, and I try to keep an open mind.

But I do wish you'd shut up. Your points are all asinine cheerleading for NR, and you aren't convincing anyone. Much the opposite.

Only way to describe people in this thread are drug addicts.

[BigLabRat]

Only way to describe people in this thread are drug addicts.

 

 

Well, I did quite some time on NR, without much result.

 

BTW, that's "IS drug addicts," not "ARE drug addicts." "Only way IS," not "Only way ARE."

 

This isn't the first time your grammar has been crap, and usually I don't care. But in your case, it makes me suspect you're from a Russian troll farm. That would explain a lot.

 

 

[ambivalent]

well actually it should be 'is drug-addicted'.

 

Anyhow, this is OT but that may not be a bad thing - could someone lend me hand understanding this: 

 

https://link.springe...0726-010-0631-2

 

[Nate-2004]

Regarding fusion, I was reading about how curcumin and sulforaphane synergize to reduce a basket of inflammatory markers (PMID 18841446). I took them both last night (just one pill each), and got a large energy boost and a poor night's sleep. I won't be doing that again. A dose the following morning was great though for energy and a 5 mile run.

 

I wonder if there is any synergistic benefit for fusion from this combo.

 

Sulforaphane for sure, it's all over this thread, I dunno about curcumin but I've been taking both during the fusion half.

[Andey]

I'm not the ideal test subject because I take a lot of other supplements, and for some unknown reason, my HbA1c is higher than it should with an average blood glucose in the 80s (mg/dL)  (measured by testing 30 min and 1 hour after each meal plus every 2 hours for 24 hours).

Also my HbA1c does not correlate properly with my blood sugar. (My HbA1c is much higher than it should be for my blood glucose levels)

 

have you checked MCV number?  If you have smallish RBC it could mean that you have beta thalassemia genetic trait that prevents proper HbA1C results.

[Turnbuckle]

 

You can’t deny that hundreds of thousands people are getting fantastic results from NR just in a short period of time....I have not heard people taking NAM claiming getting younger.

 

But I CAN deny that "hundreds of thousands of people" are taking NR and "getting fantastic results." There isn't data on the results in hundreds of thousands of people. There aren't even hundreds of thousands of people making favorable statements.

 

And I don't care what you have 'heard' about 'claiming getting younger.' (Actually, quite a few people made that claim about niacin in the 50s and 60s. There are whole books on niacin as a miracle nutrient.) A few enthusiastic anecdotes doesn't convince me of anything.

 

I haven't been responding to most of your cherry-picked science, because I'm a scientist (yes, professionally, and, yes, I have a PhD), and I've learned that it's pointless to argue with people who have already made up their minds and don't actually know anything.

 

At this point, nothing is as all that clear in the NAD+ world; we've only scratched the surface, and I try to keep an open mind.

 

But I do wish you'd shut up. Your points are all asinine cheerleading for NR, and you aren't convincing anyone. Much the opposite.

 

 

 

It's a shame that pests like MikeDC are allowed to ruin threads for their own commercial purposes.  Though I imagine if people got sufficiently annoyed they might begin posting the truth about NR on vendors' sites. The effects of NR for pennies a day--that sort of thing could take off.

[PAMPAGUY]

Turnbuckle,

 

I'm ordering supplements for my protocol, but where is the best place to buy broccoli sprout extract with sulforaphane for the fusion portion.  .5-1g, most supplements are in the 400 mcg range.  Since, I will be doing two days of fission, then 2 days of fusion, what about stearic acid even with its long half life?   Any other best sites for all of these supplements would be appreciate.

Thanks again.

[Turnbuckle]

Turnbuckle,

 

I'm ordering supplements for my protocol, but where is the best place to buy broccoli sprout extract with sulforaphane for the fusion portion.  .5-1g, most supplements are in the 400 mcg range.  Since, I will be doing two days of fission, then 2 days of fusion, what about stearic acid even with its long half life?   Any other best sites for all of these supplements would be appreciate.

Thanks again.

 

I've only tried one--from Vitacost--and it was in that range. It seems to work though it isn't as good as stearic acid. And that's one advantage of a 3 day fission / 3 day fusion cycle--that you can take stearic acid only once--on the first day of fusion--and by the fourth day when you start fission again, it has cleared out. (Or down to about 5% of the original dose, and you might be getting more than that from your diet.)

 

Note for the first day of fusion: I find it convenient to mix stearic acid (fusion) with leucine (biogenesis) and lecithin in a glass--4 to 5 grams of each--stirring with a spoon while adding water drop-wise until a paste is formed, then topping off with fruit juice. 

[Nate-2004]

PAMPAGUY Just make sure if you're getting broccoli extract (glucoraphanin) that you're also getting the myrosinase, Jarrow BroccoMax is the only one of maybe 3 supplements out there that include it. Otherwise little to no sulforaphane. Might even help to take it with a blended kale smoothie of some sort.  I might go back to just growing sprouts again once I move to a new place.

[pamojja]

 

I'm not the ideal test subject because I take a lot of other supplements, and for some unknown reason, my HbA1c is higher than it should with an average blood glucose in the 80s (mg/dL)  (measured by testing 30 min and 1 hour after each meal plus every 2 hours for 24 hours).

Also my HbA1c does not correlate properly with my blood sugar. (My HbA1c is much higher than it should be for my blood glucose levels)

 

Wow, so you took the effort and tested every 2 hours during 24 hrs? For that you would have to get up from sleep repeatedly! Would you mind sharing a typical 24 hour blood glucose curve?

 

Always wondered how blood glucose behaves during sleep. Since I had an average (9 years of testing) fasting of 101 mg/dl, an avg. 1 hr spike (my highest) at 126 mg/dl, and therefore calculated a mean at 116 mg/dl. Which would give a calculated HbA1c of 5.7%. Actually measured it was 5.1% only. Which calculated back should give a mean BG of 99 mg/dl. Therefore the opposite deviation in my case from yours.

 

Though in my case 0.5% HbA1c deviation could be explained with my high vitamin C intake (study).

 

To take this post more on topic again, here my Ribbose intake, beside 3 g of B3 and resulting HbA1c during the years:

Year HbA1c Ribbose mg/d
2009  4.8%     0
2010  4.9%     0
2011  4.8%  2300
2012  5.4%  3900
2013  5.1%  2400
2014  5.0%  1000
2015  5.4%  1700
2016  5.0%  3300
2017  4.9%  3800

Doesn't seem particularly associated. Especially considering that the rise in 2012 was preceded by my blood sugar going out of control (persistent 124 mg/dl fasting) after a 1 week water-fast. On top of it a chronic bronchitis during that whole year with worst CRP and fibrinogen during these years. The highest ever measured Hb1Ac was 6.2% at the start of 2015 in India (above averaged out with 2 additional measurements during that year).

 

Edited by pamojja, 26 October 2017 - 10:54 AM.

[MikeDC]

https://www.ncbi.nlm...mentation sirt1

[Nate-2004]

https://www.ncbi.nlm...mentation sirt1

 

Nicotinamide (NAM), or vitamin B3, is an essential coenzyme for ATP synthesis and an inhibitor of sirtuin 1. Recently, conflicting results were reported regarding the treatment of NAM in type 2 diabetes and obesity. The aim of this study was to determine whether and how long-term treatment with NAM at lower dose would affect insulin sensitivity in mice fed chow diet. We treated mice with NAM (100 mg/kg/day) and normal chow for 8 weeks. Strikingly, NAM induced glucose intolerance and skeletal muscle lipid accumulation in nonobese mice. NAM impaired mitochondrial respiration capacity and energy production in skeletal muscle, in combination with increased expression of the mediators for mitophagy (p62, PINK1, PARK2 and NIX) and autophagy (FOXO3, Bnip3, CTSL, Beclin1 and LC-3b). Next, we treated mice with high-fat diet (HFD) and resveratrol (RSV; 100 mg/kg/day) for 8 weeks. RSV protected against HFD-induced insulin resistance and obesity. HFD increased skeletal muscle lipid content as well as NAM, but this increase was attenuated by RSV. In contrast to NAM, HFD enhanced fatty acid oxidative capacity. Muscle transcript levels of genes for mitophagy and autophagy were largely suppressed by HFD, whereas RSV did not rescue these effects. These differences suggest that skeletal muscle autophagy may represent adaptive response to NAM-induced lipotoxicity, whereas reduced autophagy in skeletal muscle may promote HFD-induced lipotoxicity. Our results demonstrate that chronic NAM supplementation in healthy individuals, although at lower dose than previously reported, is still detrimental to glucose homeostasis and skeletal muscle lipid metabolism.

 

Is it an inhibitor of sirt 1? I thought this was disproven.

[able]

 

https://www.ncbi.nlm...mentation sirt1

 

 

 

Nicotinamide (NAM), or vitamin B3, is an essential coenzyme for ATP synthesis and an inhibitor of sirtuin 1. Recently, conflicting results were reported regarding the treatment of NAM in type 2 diabetes and obesity. The aim of this study was to determine whether and how long-term treatment with NAM at lower dose would affect insulin sensitivity in mice fed chow diet. We treated mice with NAM (100 mg/kg/day) and normal chow for 8 weeks. Strikingly, NAM induced glucose intolerance and skeletal muscle lipid accumulation in nonobese mice. NAM impaired mitochondrial respiration capacity and energy production in skeletal muscle, in combination with increased expression of the mediators for mitophagy (p62, PINK1, PARK2 and NIX) and autophagy (FOXO3, Bnip3, CTSL, Beclin1 and LC-3b). Next, we treated mice with high-fat diet (HFD) and resveratrol (RSV; 100 mg/kg/day) for 8 weeks. RSV protected against HFD-induced insulin resistance and obesity. HFD increased skeletal muscle lipid content as well as NAM, but this increase was attenuated by RSV. In contrast to NAM, HFD enhanced fatty acid oxidative capacity. Muscle transcript levels of genes for mitophagy and autophagy were largely suppressed by HFD, whereas RSV did not rescue these effects. These differences suggest that skeletal muscle autophagy may represent adaptive response to NAM-induced lipotoxicity, whereas reduced autophagy in skeletal muscle may promote HFD-induced lipotoxicity. Our results demonstrate that chronic NAM supplementation in healthy individuals, although at lower dose than previously reported, is still detrimental to glucose homeostasis and skeletal muscle lipid metabolism.

 

Is it an inhibitor of sirt 1? I thought this was disproven.

 

 

Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.

 

 

This review above made a pretty good case that although NAM inhibits Sirt1 in vitro, once it is in the body and elevates NAD+, the longer effect is to activate Sirt1.  

 

They also show some earlier studies were faulty.

 

But I don't think they PROVE either way - just cast doubt on the Nam inhibits Sirt1 theme.

 

Note the study Mike linked is older.  But it does show some sirt1 expression charts that I haven't looked at enough yet, and likely won't be able to tell if that is really conclusive of anything myself.

[resting]

There is something to it. I did have a 'you look younger that you did" and that was just a matter of weeks. Did take me back a bit as totally unexpected.

[Kirito]

Found this interesting.

 

"Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C. elegans via maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity"

 

http://www.sciencedi...550413117306125

[MikeDC]

Insulin sensitivity is related to Sirt1 activity. If NAM reduces insulin sensitivity, what is the logical conclusion about NAM being Sirt1 inhibitor?

Many papers like this linking insulin sensitivity to sirt1。

https://www.ncbi.nlm...nsitivity sirt1

[Turnbuckle]

There is something to it. I did have a 'you look younger that you did" and that was just a matter of weeks. Did take me back a bit as totally unexpected.

 

 

There have been a number of supplements and protocols discussed on this thread. Which are you referring to?

[Nate-2004]

https://medicalxpres...lthy-aging.html

 

Manipulating mitochondrial networks inside cells—either by dietary restriction or by genetic manipulation that mimics it—may increase lifespan and promote health, according to new research from Harvard T.H. Chan School of Public Health.

 

The study, published online October 26, 2017 in Cell Metabolism, sheds light on the basic biology involved in cells' declining ability to process energy over time, which leads to aging and age-related disease, and how interventions such as periods of fasting might promote healthy aging.

Mitochondria—the energy-producing structures in cells—exist in networks that dynamically change shape according to energy demand. Their capacity to do so declines with age, but the impact this has on metabolism and cellular function was previously unclear. In this study, the researchers showed a causal link between dynamic changes in the shapes of mitochondrial networks and longevity.

The scientists used C. elegans (nematode worms), which live just two weeks and thus enable the study of aging in real time in the lab. Mitochondrial networks inside cells typically toggle between fused and fragmented states. The researchers found that restricting the worms' diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or "youthful" state. In addition, they found that these youthful networks increase lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.

"Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging. Understanding why this is the case is a crucial step towards being able to harness the benefits therapeutically," said Heather Weir, lead author of the study, who conducted the research while at Harvard Chan School and is now a research associate at Astex Pharmaceuticals. "Our findings open up new avenues in the search for therapeutic strategies that will reduce our likelihood of developing age-related diseases as we get older."

"Although previous work has shown how intermittent fasting can slow aging, we are only beginning to understand the underlying biology," said William Mair, associate professor of genetics and complex diseases at Harvard Chan School and senior author of the study. "Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity."

Next steps for the researchers including testing the role mitochondrial networks have in the effect of fasting in mammals, and whether defects in mitochondrial flexibility might explain the association between obesity and increased risk for age-related diseases.

 Explore further: On-and-off fasting helps fight obesity

More information: "Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling," Heather J. Weir, Pallas Yao, Frank K. Huynh, Caroline C. Escoubas, Renata L. Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D. Hirschey, and William B. Mair, Cell Metabolism, online October 26, 2017, DOI: 10.1016/j.cmet.2017.09.024

Journal reference: Cell Metabolism  

[PAMPAGUY]

Turnbuckle,

I'm ordering supplements for my protocol, but where is the best place to buy broccoli sprout extract with sulforaphane for the fusion portion. .5-1g, most supplements are in the 400 mcg range. Since, I will be doing two days of fission, then 2 days of fusion, what about stearic acid even with its long half life? Any other best sites for all of these supplements would be appreciate.
Thanks again.

I've only tried one--from Vitacost--and it was in that range. It seems to work though it isn't as good as stearic acid. And that's one advantage of a 3 day fission / 3 day fusion cycle--that you can take stearic acid only once--on the first day of fusion--and by the fourth day when you start fission again, it has cleared out. (Or down to about 5% of the original dose, and you might be getting more than that from your diet.)

Note for the first day of fusion: I find it convenient to mix stearic acid (fusion) with leucine (biogenesis) and lecithin in a glass--4 to 5 grams of each--stirring with a spoon while adding water drop-wise until a paste is formed, then topping off with fruit juice.

[PAMPAGUY]

Turnbuckle or anyone who can help,

 

I have ordered all the supplements for my Fission/Fusion experiment.  I will be using NR and Stearic Acid.(only 1 day a week)  Seems the stearic acid is a waxy substance, and that will be different ingesting it.  2 days Fission then 2 days Fusion with 3 days off at first.  Working my way up to a weekly 3+3 with 1 day off in time.  I found broccoli sprout extract, 500 mg (per capsule) with 5% sulforaphane taking 2 capsules.  Do I skip the broccoli on the 1st. day when taking the Stearic Acid?

 

I have been taking 500 mg NR twice a week until I get started.  I would like to say that the 500 mg kicks my ass for that day.  Afraid of what 2-3 gm will do.  I feel really tired and out of it when I take the NR for most of the day.  Clearing out those Zombies is hard work.

 

Is there anything I can do to help with the feeling of being wiped out??  All I do is lay around and over eat.

 

Will post this on NR experiences forum as well.