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Valter Longo yet another (interesting) podcast

Valter Longo FMD phantom carbon sources

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#1 mccoy

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Posted 06 June 2018 - 09:19 AM

Valter Longo must be one of the most interviewed guys in the latest coupla years.

 

I just listened to the stemtalk interview (Ken Ford is usually biased on the ketogenic diet, but he's been evidently able to overcome this bias), where new aspects on his proposals are underlined: IGF-1 and its sweet spot, local and general IGF-1. No coffe when fasting and when on his FMD.

 

One pretty interesting issue is that about the 'phantom carbon sources', nutrients which are utilized by the body but not recognized as nutrients. Fibers? Else?

 

I googled  'phantom carbon sources' but found no relevant results so far .

 

https://www.ihmc.us/...s-to-longevity/


Edited by mccoy, 06 June 2018 - 09:20 AM.

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#2 mccoy

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Posted 06 June 2018 - 09:30 AM

 The carbon sources hint is at about 27:35, they are also calle 'carbon source substitutes' but again my search yielded no relevant results


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#3 Sibiriak

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Posted 12 June 2018 - 01:09 AM

Mccoy,   a Google search for carbon sources that activate pro-growth pathways  or  carbon sources that activate pro-pro-aging pathways  yielded some apparently relevant articles.  I haven't had the time yet to delve into them.

 

 

Replicative and Chronological Aging in Saccharomyces cerevisiae

 
 
One issue surrounding studies of replicative aging in yeast involves the choice of growth conditions, which can have major effects on experimental outcome (see section on chronological life span below). For the vast majority of replicative aging studies, growth on rich medium in the presence of 2% glucose (YPD, Yeast Peptone Dextrose) is the method of choice. It is clear, however, that life span can be affected by these choices. For instance, lowering glucose concentration, a condition that is used to model dietary (or calorie) restriction in multicellular eukaryotes, causes life span extension in many, but not all, strain backgrounds. Alternate carbon sources have also been tested to a lesser extent. Budding yeast is a facultative anaerobe that generates most of its energy in the presence of ample glucose through fermentation, with only limited respiratory metabolism. Since most mammalian tissues rely primarily on respiration rather than fermentation, it has been argued that use of a respiratory carbon source such as glycerol may make for more relevant comparison to human aging (Botta et al., 2011). This assertion has yet to be rigorously evaluated. A relatively small number of studies have also examined RLS using synthetic defined (SD) medium, which is commonly used in the chronological life span assay (below), but a direct comparison of life span on SD versus YPD has not been performed. In summary, there is a need for a broader understanding for how different environmental factors, including the nutritional status of the growth medium, influence yeast RLS.

 

 

The article has many more references to carbon sources-- the quote is just an example.  It's a dense article and I haven't digested it in the least.

 

 

Also Google carbon source substitution.

 

 

Tor1/Sch9-Regulated Carbon Source Substitution Is as Effective as Calorie Restriction in Life Span Extension

Min Wei ,Paola Fabrizio ,Federica Madia,Jia Hu,Huanying Ge,Lei M. Li,Valter D. Longo

 

Published: May 8, 2009

https://doi.org/10.1...al.pgen.1000467

 

 

 

Abstract The effect of calorie restriction (CR) on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K) is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Δ, tor1Δ, and ras2Δ mutants, was sufficient to reverse chronological life span extension in sch9Δ mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

 

 

Longo et al have an article in the book "Calorie Restriction, Longevity and Aging" (2010)  where they briefly discuss glycerol and carbon source substitution (p.101-102), citing the above mentioned article.

 

https://books.google...tution"&f=false

 

In contrast with glucose and ethanol, presence of either carbon source promotes aging,  glycerol  not only does not shorten life span of DR-ed yeast, its uptake and utilization may contribute to long term survival (Wei et al., 2008).  Taken together, the data  suggest that genetically induced "carbon source substitution" of the pro-aging ethanol with the neutral glycerol in long-lived mutants creates a DR-like environment.

 

 

 

There are many articles to read!    I await you thorough review and analysis.


Edited by Sibiriak, 12 June 2018 - 03:31 AM.


#4 Sibiriak

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Posted 12 June 2018 - 02:33 AM

No coffee when fasting and when on his FMD.

 

Longo does say that if you are several days into the FMD and you find yourself thinking of quitting because of caffeine withdrawal headaches,  you can go ahead and drink one cup a day.



#5 mccoy

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Posted 12 June 2018 - 04:57 PM

Good find Sibiriak, so from the above it would seem  that Valter Longo himself has been studying those carbon sources substitutes in his experiments on yeasts, extendign the use of some glycerol  to humans during the FMD.

We don't have a dose though, although probably not much can be added to a tea. Looking forward to read some of the articles you cited, although delving into the metabolism of yeasts sure sounds a pretty adventurous reading.


Edited by mccoy, 12 June 2018 - 05:03 PM.

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P(Ai|E)=(P(E|Ai)P(Ai))/P(E)


#6 Sibiriak

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Posted 12 June 2018 - 11:24 PM

So apparently  glycerol  is used in the FMD for two reasons: 1) to lessen the loss of muscle mass; 2) to sweeten/ thicken the drinks to make them more satisfying while avoiding the health/longevity downsides of other sweeteners.



#7 Sibiriak

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Posted 13 June 2018 - 06:42 AM

Another Longo article making similar points about glycerol.

 

Fasting: Molecular Mechanisms and Clinical Applications

 

Adaptive responses to fasting in mammals

In most mammals, the liver serves as the main reservoir of glucose, which is stored in the form of glycogen. In humans, depending upon their level of physical activity, 12 to 24 hours of fasting typically results in a 20% or greater decrease in serum glucose and depletion of the hepatic glycogen, accompanied by a switch to a metabolic mode in which non-hepatic glucose, fat-derived ketone bodies and free fatty acids are used as energy sources (Figures 2 and and3).3). Whereas most tissues can utilize fatty acids for energy, during prolonged periods of fasting, the brain relies on the ketone bodies β-hydroxybutyrate and acetoacetate in addition to glucose for energy consumption (Figure 3B). Ketone bodies are produced in hepatocytes from the acetyl-CoA generated from β oxidation of fatty acids released into the bloodstream by adipocytes, and also by the conversion of ketogenic amino acids.

 

After hepatic glycogen depletion, ketone bodies, fat-derived glycerol, and amino acids account for the gluconeogenesis-dependent generation of approximately 80 grams/day of glucose, which is mostly utilized by the brain. Depending on body weight and composition, the ketone bodies, free fatty acids and gluconeogenesis allow the majority of human beings to survive 30 or more days in the absence of any food and allow certain species, such as king penguins, to survive for over 5 months without food (Eichhorn et al., 2011) (Figure 3C).

 

In humans, during prolonged fasting, the plasma levels of 3-β-hydroxybutyrate are about 5 times those of free fatty acids and acetoacetic acid (Figure 3A and 3B). The brain and other organs utilize ketone bodies in a process termed ketolysis, in which acetoacetic acid and 3-β-hydroxybutyrate are converted into acetoacetyl-CoA and then acetyl-CoA. These metabolic adaptations to fasting in mammals are reminiscent of those described earlier for E. coli and yeast, in which acetic acid accumulates in response to food deprivation (Gonidakis et al., 2010; Longo et al., 2012). In yeast, glucose, acetic acid and ethanol, but not glycerol which is also generated during fasting from the breakdown of fats, accelerate aging (Fabrizio et al., 2005; Wei et al., 2009).

 

Thus, glycerol functions as a carbon source that does not activate the pro-aging nutrient signaling pathways but can be catabolized by cells. It will be important to understand how the different carbon sources generated during fasting affect cellular protection and aging. and to determine whether glycerol, specific ketone bodies or fatty acids can provide nourishment while reducing cellular aging in mammals, a possibility suggested by beneficial effects of a dietary ketone precursor in a mouse model of Alzheimer’s disease (Kashiwaya et al., 2012). It will also be important to study, in various model organisms and humans, how high intake of specific types of fats (medium- vs. long-chain fatty acids, etc.) in substitution of carbohydrates and proteins influences gluconeogenesis and glucose levels as well as aging and diseases.

 


Edited by Sibiriak, 13 June 2018 - 06:42 AM.


#8 mccoy

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Posted 13 June 2018 - 04:11 PM

I have bought some glycerol from the pharmacy, I'm curious to taste it tomorrow together with my cacao powder! 


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#9 mccoy

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Posted 13 June 2018 - 04:18 PM

This is an interesting practical article on glycerol supplementation. They used 1.2 g/kg bodyweight, which is a lot. seems to boost gluconeogenesis and is an hyperhydrating agent. Easy to understand now how it can minimize muscle loss during a FMD (lesser use of muscle glycogen, lesser dehydration).

 

https://www.ncbi.nlm...les/PMC3590833/


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P(Ai|E)=(P(E|Ai)P(Ai))/P(E)


#10 Mechanism

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Posted 13 June 2018 - 05:31 PM

Nice find McCoy & Sibiriak!

Some of this work is further summarized in the lay press here:
https://m.phys.org/n...ived-yeast.html

This is not new news but an important area of longevity nutrient pathway research, namely to quote a more recent 2016 publication, Nitrogen and carbon source balance determines longevity, independently of fermentative or respiratory metabolism in the yeast Saccharomyces cerevisiae:
“data herewith highlight the balance of nitrogen and carbon sources as major longevity regulators, in parallel to what has been described for the Protein: Carbohydrate ratio in higher eukaryotic models, further establishing yeast as an up to date aging model organism.”
Source: https://www.ncbi.nlm...et-07-23033.pdf

If their reference sounds familiar, they are referring to the nutritional geometry work and “Okinawa ratio” discussed here previously:
https://watermark.si...ZXjTYcZlWpjctDw

In addition to longevity matters, Valter Longo has investigated glycerol as an isocaloric method of sustaining metabolic demands during chemotherapy while maintaining lower blood glucose:

“Although the mice on the glycerol diet ate slightly more than those on the control diet, they showed an 18% reduction in blood glucose level by day 6”
From his patent:
https://patents.just...ent/20150133370

#11 Sibiriak

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Posted 13 June 2018 - 09:43 PM

Good work, Mccoy and Mechanism.   Interesting topic.  Lot's of different angles on dietary glycerol.

 

The Prolon FMD appears to contain a very modest amount of glycerol.  It's only in the "L-drinks",  which are 20 calories each (and it's listed in the algal oil DHA supplement).   You get one L-drink per day on days 2-5.

 

https://fastlifehack...alories-macros/


Edited by Sibiriak, 14 June 2018 - 12:07 AM.


#12 mccoy

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Posted 14 June 2018 - 02:07 AM

MMMmmm, 20 kcal in the L-drinks, with no other energy sources but teh glycerin.

 

As to content of glycerin, since it's a carbohydrate = 20/4= 5 grams

 

It's more or less in line with the reccomanded amount as a pre-workout supplement, about 3 grams, as underlined in these bodybuilder's sites

 

https://www.bestwork...ol-supplements/

 

https://supplementsi...ol-pre-workout/

 

The L-drinks are part of days 2 to 5, so an intake of 5 grams of glycerol/glycerin after dinner should bring about the beneficial effects foreseen by Longo's FMD.


Edited by mccoy, 14 June 2018 - 02:10 AM.

"Data speak for themselves" -Reverend Thomas Bayes 1702-1761
P(Ai|E)=(P(E|Ai)P(Ai))/P(E)


#13 Sibiriak

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Posted 14 June 2018 - 02:37 AM

Mccoy,  are you going to be drinking glycerol drinks regularly?     



#14 Matt

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Posted 14 June 2018 - 12:22 PM

Thanks for sharing! :)



#15 mccoy

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Posted 15 June 2018 - 01:59 PM

Mccoy,  are you going to be drinking glycerol drinks regularly?     

 

That's an interesting question, to which I don't know the answer yet. I've drunk glycerol for the 1st time when starting today my 7th FMD cycle. Very sweet taste, probably it's not included among the sweeteners because of its caloric load.

 

I'll have to do some research and see if it might carry some undesired side effects. Sure some hyperhydration in the summertime won't hurt. But again, I'll have to do some search.


"Data speak for themselves" -Reverend Thomas Bayes 1702-1761
P(Ai|E)=(P(E|Ai)P(Ai))/P(E)






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