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#1 100YearsToGo

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Posted 03 October 2008 - 08:42 PM


I've been discussing this in the Bio section but now we need the supplements experts to Join in:

Autophagy is a cellular process that mediates the degradation of intracelular components.

It is over activated during starvation (e.x. calorie restriction) when the body searches for any energy source and building blocks it can find. When the signal of starvation is received the body (over) activates autophagy in all it's forms, Micro, Micro and Chaperone mediated, to sequester cytoplasm, cell organelles, damaged protein. The captured carbage is then broken down to produce usefull amino acids, fatty acids, sugars etc. Those are then used to combat the starvation problem. In the process your organs and tissues are cleaned of garbage, restoring optimal function.

Normal autophagy function declines with age leading to intracellular accumulation of junk:

http://www.jbc.org/c...ct/275/40/31505

At least in yeast, activating Chaperone Mediated Autophagy has life extension properties, While Macro and Micro Autophagy doesn't

http://www.landesbio...gy/article/6556


The cuervo papers demonstarted the power of activating chaparone mediated autophagy to restore the mouse liver to a more youthfull state:

http://blog.wired.co...r-problems.html

Sorry I liked the mouse picture :)

This is the paper:

http://www.scribd.co...epatic-Function


So the question is how can we maintain healthy autophagy function. Or how can we activate autophagy function to get rid of the intracell junk that we have allready accumulated?

It appears there are FDA aproved drugs that can do this, but are used for other stuff right now.

The article:

"They screened 256 existing drugs in use for other medical conditions and found several which induce autophagy. Two drugs are of particular interest, verapamil and clonidine. Verapamil is prescribed for high blood pressure and many people take it for years. It is an L-type calcium channel antagonist and stimulates autophagy by reducing the influx of calcium into cells. Calcium handling is known to be a problem in HD. "

http://hdlighthouse....ticleNumber=559

This is the paper:

http://www.ncbi.nlm....Pubmed_RVDocSum

I have the full paper. :)

This is exciting. Now the question...are there supplements that would induce autophagy. Most of the FDA aproved drugs have side effects.

Edited by Mind, 04 August 2009 - 06:08 PM.


#2 100YearsToGo

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Posted 03 October 2008 - 11:20 PM

F.Y.I.

"We have recently shown a novel property of trehalose in inducing mTORindependent autophagy. Trehalose enhanced the clearance of mutant huntingtin (and of A53T and A30P mutants of asynuclein), thereby reducing mutant huntingtin aggregation/toxicity.53 Trehalose treatment increased autophagic flux in a variety of mammalian cells, and we showed that these effects were mediated by intracellular trehalose.53 Furthermore, trehalose pre-treatment protected against pro-apoptotic insults by reducing mitochondrialload, as seen with rapamycin.21,53 The dual protective properties of trehalose ('autophagy induction' for enhancing clearance of aggregate-prone proteins and 'chemical chaperone' for inhibiting aggregation), coupled with its lack of toxicity, make it a possible candidate for the treatment of neurodegenerative disorders"

And:

"We have previously shown that moodstabilizing drugs, like lithium, carbamazepine and valproic acid, which all lower intracellular inositol levels,22 also induce autophagy.23 Lithium (Li+) is a monovalent cation with a hydrated ionic radiu similar to that of magnesium (Mg2+)"

from
http://www.ncbi.nlm.nih.gov/pubmed/1870422...Pubmed_RVDocSum


Edited by 100YearsToGo, 03 October 2008 - 11:21 PM.


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#3 luv2increase

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Posted 04 October 2008 - 02:14 AM

Intermittent water fasting while using maybe prevagen or lithium concurrently???

Edited by luv2increase, 04 October 2008 - 02:14 AM.


#4 caston

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Posted 04 October 2008 - 03:28 AM

Intermittent water fasting while using maybe prevagen or lithium concurrently???


Or we could do a double blind placebo controlled study to measure and graph the cellular ATP levels (e.g. dips and spikes) of emotional vampires compared to the control group.

#5 StrangeAeons

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Posted 04 October 2008 - 04:34 AM

Looked up trehalose in Wikipedia:

It is implicated in anhydrobiosis — the ability of plants and animals to withstand prolonged periods of desiccation. It has high water retention capabilities and is used in food and cosmetics. The sugar is thought to form a gel phase as cells dehydrate, which prevents disruption of internal cell organelles by effectively splinting them in position. Rehydration then allows normal cellular activity to be resumed without the major, lethal damage that would normally follow a dehydration/re-hydration cycle.

This sounds like it could have a crucial application in cryonics.

Edited by PetaKiaRose, 04 October 2008 - 04:42 AM.


#6 100YearsToGo

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Posted 04 October 2008 - 12:13 PM

Looked up trehalose in Wikipedia:

It is implicated in anhydrobiosis — the ability of plants and animals to withstand prolonged periods of desiccation. It has high water retention capabilities and is used in food and cosmetics. The sugar is thought to form a gel phase as cells dehydrate, which prevents disruption of internal cell organelles by effectively splinting them in position. Rehydration then allows normal cellular activity to be resumed without the major, lethal damage that would normally follow a dehydration/re-hydration cycle.

This sounds like it could have a crucial application in cryonics.


Trehalose is a sugar. It can safely be used. It has been granted FDA GRAS (Substances Generally Recognized as Safe ). it is actually used in some sport drinks. You can buy it by the bag.

http://www.naturalwa...k/trehalose.php

I've seen reports that in In high doses it may induce diarrhea is some individuals. In the paper I posted it seems it had the most impact in a variety of cells. It has a dual effect:

"Trehalose has been termed as 'chemical chaperone' as it influences protein folding through direct protein–trehalose interactions, and thus it protects cells against various environmental stresses by preventing protein denaturation"

and

"Trehalose treatment increased autophagic flux in a variety of mammalian cells, and we showed that these effects were mediated by intracellular trehalose."

The second effect of trehalose on autophagy was just recently discovered by Rubinsztein. Other interesting studies are:



Beattie, G. M., J. H. Crowe, A. D. Lopez, V. Cirulli, C. Ricordi and A. Hayek (1997). "Trehalose: a cryoprotectant that enhances recovery and preserves function of human pancreatic islets after long-term storage." Diabetes 46(3): 519-23.


Colaco, C., J. Kampinga and B. Roser (1995). "Amorphous stability and trehalose." Science 268(5212): 788.

Colaco, C., S. Sen, M. Thangavelu, S. Pinder and B. Roser (1992). "Extraordinary stability of enzymes dried in trehalose: simplified molecular biology." Biotechnology (N Y) 10(9): 1007-11.

Crowe, J. H., F. Tablin, W. F. Wolkers, K. Gousset, N. M. Tsvetkova and J. Ricker (2003). "Stabilization of membranes in human platelets freeze-dried with trehalose." Chem Phys Lipids 122(1-2): 41-52.

Crowe, L. M. (2002). "Lessons from nature: the role of sugars in anhydrobiosis." Comp Biochem Physiol A Mol Integr Physiol 131(3): 505-13.

Davies, J. E., S. Sarkar and D. C. Rubinsztein (2006). "Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy." Hum Mol Genet 15(1): 23-31.

Erdag, G., A. Eroglu, J. Morgan and M. Toner (2002). "Cryopreservation of fetal skin is improved by extracellular trehalose." Cryobiology 44(3): 218-28.

Eroglu, A., M. J. Russo, R. Bieganski, A. Fowler, S. Cheley, H. Bayley and M. Toner (2000). "Intracellular trehalose improves the survival of cryopreserved mammalian cells." Nat Biotechnol 18(2): 163-7.

Liu, R., H. Barkhordarian, S. Emadi, C. B. Park and M. R. Sierks (2005). "Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42." Neurobiol Dis 20(1): 74-81.

Nguyen, H., M. Bonin, M. Kuhn, C. Holzmann, S. v. Horsten and O. Riess (2005). Gene expression pattern in HD transgenic rats and HD knock-in mice: specific effects of trehalose treatment. Society for Neuroscience, Washington, DC.

Oliver, A. E., K. Jamil, J. H. Crowe and F. Tablin (2004). "Loading Human Mesenchymal Stem Cells with Trehalose by Fluid-Phase Endocytosis." Cell Preservation Technology 2(1): 35-49.

Richards, A. B., S. Krakowka, L. B. Dexter, H. Schmid, A. P. Wolterbeek, D. H. Waalkens-Berendsen, A. Shigoyuki and M. Kurimoto (2002). "Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies." Food Chem Toxicol 40(7): 871-98.

Singer, M. A. and S. Lindquist (1998). "Multiple effects of trehalose on protein folding in vitro and in vivo." Mol Cell 1(5): 639-48.

Strickley, R. G. and B. D. Anderson (1997). "Solid-state stability of human insulin. II. Effect of water on reactive intermediate partitioning in lyophiles from pH 2-5 solutions: stabilization against covalent dimer formation." J Pharm Sci 86(6): 645-53.

Suzuki, T., A. Boediono, M. Takagi, S. Saha and C. Sumantri (1996). "Fertilization and development of frozen-thawed germinal vesicle bovine oocytes by a one-step dilution method in vitro." Cryobiology 33(5): 515-24.

Tanaka, M., Y. Machida, S. Niu, T. Ikeda, N. R. Jana, H. Doi, M. Kurosawa, M. Nekooki and N. Nukina (2004). "Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease." Nat Med 10(2): 148-54.

van Elburg, R. M., J. J. Uil, F. T. Kokke, A. M. Mulder, W. G. van de Broek, C. J. Mulder and H. S. Heymans (1995). "Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars." J Pediatr Gastroenterol Nutr 20(2): 184-8.

Walsh, D. M., I. Klyubin, G. M. Shankar, M. Townsend, J. V. Fadeeva, V. Betts, M. B. Podlisny, J. P. Cleary, K. H. Ashe, M. J. Rowan and D. J. Selkoe (2005). "The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention." Biochem Soc Trans 33(Pt 5): 1087-90. Zhang, X. B., K. Li, K. H. Yau, K. S. Tsang, T. F. Fok, C. K. Li, S. M. Lee and P. M. Yuen (2003). "Trehalose ameliorates the cryopreservation of cord blood in a preclinical system and increases the recovery of CFUs, long-term culture-initiating cells, and nonobese diabetic-SCID repopulating cells." Transfusion 43(2): 265-72.


Edited by 100YearsToGo, 04 October 2008 - 12:16 PM.


#7 StrangeAeons

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Posted 04 October 2008 - 04:19 PM

The diarrhea is due to an osmotic effect; many large sugar molecules used as sweeteners such as mannitol and sorbitol due the same thing. What's really interesting to me is its role in vitrification, and whether or not it's being used in cryopreservatives. The wikipedia article points out that it is a poor sweetener because it is only 40% as sweet as sucrose and poorly soluble at normal temperatures. Still, it is clearly an amazing molecule as seen in nature, and the data you've got on autophagy makes it even sweeter.

#8 100YearsToGo

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Posted 04 October 2008 - 05:54 PM

The diarrhea is due to an osmotic effect; many large sugar molecules used as sweeteners such as mannitol and sorbitol due the same thing. What's really interesting to me is its role in vitrification, and whether or not it's being used in cryopreservatives. The wikipedia article points out that it is a poor sweetener because it is only 40% as sweet as sucrose and poorly soluble at normal temperatures. Still, it is clearly an amazing molecule as seen in nature, and the data you've got on autophagy makes it even sweeter.


Yes I like this molecule too. Another nice property is that it will not hydrolyse to its component parts and subsequently take part in maillard reactions with amino acids and proteins like other sugars. However the body will break down part of it converting it into glucose. It is incompletely digested to glucose in the small intestine. Once in the blood trehalose apears to be further broken down to glucose by other organs:

"Trehalose entering the circulating blood is converted to glucose by trehalase in serum, kidney, liver, and bile, depending on the species (van Handel, 1969; Labat-Robert, 1982; Arola et al., 1999). The trehalose that is not converted to glucose is excreted in the urine of rats, guinea-pigs, and birds, which lack renal trehalase. In mice, rabbits, dogs, pigs, and humans, trehalase in the brush border of the proximal tubular cells of the kidney would be expected to cleave the excreted trehalose to glucose (Demelier et al., 1975; Niederst & Dauça, 1985; Riby et al., 1990). "

http://www.inchem.or...ono/v46je05.htm

Edited by 100YearsToGo, 04 October 2008 - 06:14 PM.


#9 tintinet

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Posted 05 October 2008 - 06:24 PM

Paul Wakfer's autophagy info at Morelife.org. See Acipimox information and references.

Edited by tintinet, 05 October 2008 - 06:27 PM.


#10 100YearsToGo

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Posted 05 October 2008 - 09:02 PM

Paul Wakfer's autophagy info at Morelife.org. See Acipimox information and references.



Thanks. Note that a (mild) form of calorie restriction is necessary for Acipimox to work.

"We have observed that Acipimox does not affect autophagy and biomarkers of aging if given to rats fed ad libitum (unpublished). Present observation shows that treatment with the antilipolytic drug intensifies the anti-aging effects of submaximal calorie restrictions and makes them maximal."

Edited by 100YearsToGo, 05 October 2008 - 09:04 PM.


#11 100YearsToGo

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Posted 17 December 2008 - 02:35 AM

This recentstudy shows that calory restricted yeast cell produce trehalose to prevent clumping together of misfolded protein:

"Another typical sign of aging is the accumulation of clumps of misfolded proteins. In people, such clumps are a hallmark of degenerative diseases such as Alzheimer’s. Calorie restriction boosted the yeast cells’ production of a sugar called trehalose, Titorenko reports. This sugar binds to misfolded proteins and prevents them from clumping together. "

http://www.sciencene..._long_and_alter

The same scientist now reports finding 5 new small molecules that combats aging in the yeast cell. Can't wait to see the study:

I suspect trehalose is one of the small molecules.

http://www.physorg.c...s148658925.html

#12 geddarkstorm

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Posted 17 December 2008 - 04:30 AM

This recentstudy shows that calory restricted yeast cell produce trehalose to prevent clumping together of misfolded protein:

"Another typical sign of aging is the accumulation of clumps of misfolded proteins. In people, such clumps are a hallmark of degenerative diseases such as Alzheimer's. Calorie restriction boosted the yeast cells' production of a sugar called trehalose, Titorenko reports. This sugar binds to misfolded proteins and prevents them from clumping together. "

http://www.sciencene..._long_and_alter

The same scientist now reports finding 5 new small molecules that combats aging in the yeast cell. Can't wait to see the study:

I suspect trehalose is one of the small molecules.

http://www.physorg.c...s148658925.html


Very, very interesting. Hmm.. it sounds like humans don't naturally produce it ("No vertebrate has been shown to synthesize trehalose" ref), but also break it down very rapidly. That's a bummer. I wish I could find more in vivo kinetics data on it... maybe it lasts long enough in serum, and is taken up into and stored in cells enough to have an effect and justify use. This is definitely something to keep an eye on, thanks 100YearsToGo.


@PetaKiaRose: Here's a little paper on it being used as a cryoprotected for livers at least, lol

#13 100YearsToGo

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Posted 17 December 2008 - 01:17 PM

This recentstudy shows that calory restricted yeast cell produce trehalose to prevent clumping together of misfolded protein:

"Another typical sign of aging is the accumulation of clumps of misfolded proteins. In people, such clumps are a hallmark of degenerative diseases such as Alzheimer's. Calorie restriction boosted the yeast cells' production of a sugar called trehalose, Titorenko reports. This sugar binds to misfolded proteins and prevents them from clumping together. "

http://www.sciencene..._long_and_alter

The same scientist now reports finding 5 new small molecules that combats aging in the yeast cell. Can't wait to see the study:

I suspect trehalose is one of the small molecules.

http://www.physorg.c...s148658925.html


Very, very interesting. Hmm.. it sounds like humans don't naturally produce it ("No vertebrate has been shown to synthesize trehalose" ref), but also break it down very rapidly. That's a bummer. I wish I could find more in vivo kinetics data on it... maybe it lasts long enough in serum, and is taken up into and stored in cells enough to have an effect and justify use. This is definitely something to keep an eye on, thanks 100YearsToGo.


@PetaKiaRose: Here's a little paper on it being used as a cryoprotected for livers at least, lol


Bummer...I expected your usual 3 page response. :)

These mice were fed trehalose:

"Here, we show that trehalose reduces aggregate formation and toxicity of mutant PABPN1 in cell models. Furthermore, oral administration of trehalose attenuated muscle weakness, reduced aggregate formation and decreased the number of TUNEL-labelled nuclei in skeletal muscle in an OPMD transgenic mouse model. Thus, anti-aggregation therapy may prove effective in the treatment of human OPMD. "

http://hmg.oxfordjou...nt/full/15/1/23

Edited by 100YearsToGo, 17 December 2008 - 01:18 PM.


#14 FunkOdyssey

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Posted 17 December 2008 - 02:51 PM

I think lithium sounds like the most practical agent that has been mentioned in this thread so far. There's no evidence that trehalose becomes systemically available in humans -- we all have a trehalase enzyme in our gut that splits it into glucose.

#15 100YearsToGo

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Posted 17 December 2008 - 05:29 PM

I think lithium sounds like the most practical agent that has been mentioned in this thread so far. There's no evidence that trehalose becomes systemically available in humans -- we all have a trehalase enzyme in our gut that splits it into glucose.


There is evidence in rats and mice. Mice who received 2% trehalose in drinking water had trehalose (0.11 +/- O.O2 nmol/ug protein) present in brain homogenates. Mice use the same trehalase enzyme that is supposed to break trehalose down into clucose. Also remember, a small fraction (0.5%) is probably absorbed by passive diffusion, as has been showed in other sacharides. (van Elburg et al. 1995 )

Note: I've been taking trehalose for a couple of months. During this period I've noticed better memory, brain stays alert even after a tiresome day. Can endure heavy friday drinking without colapsing the following day. Placebo?

Edited by 100YearsToGo, 17 December 2008 - 05:34 PM.


#16 FunkOdyssey

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Posted 17 December 2008 - 05:41 PM

What dose have you been taking and how do you divide it up, with consideration of the fact that a majority will be absorbed as straight glucose? With food, empty stomach?

Note: I've been taking trehalose for a couple of months. During this period I've noticed better memory, brain stays alert even after a tiresome day. Can indure heavy friday drinking without colapsing the following day. Placebo?


The trehalose may be responsible, or it may be placebo. Things like alertness and better memory are difficult to quantify and are very vulnerable to the placebo effect. Exhibit A - the enduring popularity of the 'racetams. :)

#17 lynx

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Posted 17 December 2008 - 05:50 PM

http://www.hdac.org/...ticleNumber=252

Trehalose is a food product which hasn't been available retail in the US before. The dose we use in HDDW trials is 25 gms three times a day. The price they quote means about $1/day. Though our numbers are small, the trend in our trials suggests that trehalose is helpful at all stages of HD, but the earlier the better.

If you use this I recommend you start with 10 grams a dose and work your way up. Unfortunately about 25% of HDDW participants had diarrhea. I think it is ok, even good, in diabetics. Its use resulted in better control of sugars in one of my Huntington's patients.


-- LaVonne Veatch Goodman, M.D.

Although trehalose absorption in humans has not been well studied, a small fraction (0.5%) is likely to be absorbed by passive diffusion, as has been demonstrated for other dissacharides (van Elburg et al. 1995).



#18 100YearsToGo

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Posted 17 December 2008 - 06:01 PM

What dose have you been taking and how do you divide it up, with consideration of the fact that a majority will be absorbed as straight glucose? With food, empty stomach?

Note: I've been taking trehalose for a couple of months. During this period I've noticed better memory, brain stays alert even after a tiresome day. Can indure heavy friday drinking without colapsing the following day. Placebo?


The trehalose may be responsible, or it may be placebo. Things like alertness and better memory are difficult to quantify and are very vulnerable to the placebo effect. Exhibit A - the enduring popularity of the 'racetams. :)



I just replaced regular sugar in my household with trehalose, I take it with coffee, thee, chocolate, cereal etc...No problems. You have to use twice the amount to get the same sweetness as regular sugar. It tastes the same.

#19 FunkOdyssey

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Posted 17 December 2008 - 06:33 PM

Just to play devil's advocate, the possibility strikes me that subjective benefits in cognition may be due simply to the effects of glucose on the brain. Many studies have documented a boost in cognitive performance after consumption of a significant quanitity of glucose vs. placebo -- it is the brain's preferred fuel after all.

It does sound like trehalose is really doing something positive in Huntington's patients.

#20 geddarkstorm

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Posted 17 December 2008 - 09:30 PM

Bummer...I expected your usual 3 page response. :)

These mice were fed trehalose:

"Here, we show that trehalose reduces aggregate formation and toxicity of mutant PABPN1 in cell models. Furthermore, oral administration of trehalose attenuated muscle weakness, reduced aggregate formation and decreased the number of TUNEL-labelled nuclei in skeletal muscle in an OPMD transgenic mouse model. Thus, anti-aggregation therapy may prove effective in the treatment of human OPMD. "

http://hmg.oxfordjou...nt/full/15/1/23


Haha, sorry to disappoint. Hm, it is interesting stuff. It's too bad they only devoted one figure to the mice as far as I could tell, and didn't really look at the amount of trehalose that was staying in their system (unless I missed that part).

FunkOdyssey does make a good point about the conversion to glucose, in the sense that when you take a ton of trehalose, you're also taking a ton of glucose. Then again, the soda I like to drink has 40 blood grams of sugar a can, and the stuff here suggests taking only 10 grams of trehalose, so you definitely won't be over hopping yourself up on glucose...

Sounds like a fair replacement to me :)

#21 100YearsToGo

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Posted 17 December 2008 - 10:00 PM

Bummer...I expected your usual 3 page response. :)

These mice were fed trehalose:

"Here, we show that trehalose reduces aggregate formation and toxicity of mutant PABPN1 in cell models. Furthermore, oral administration of trehalose attenuated muscle weakness, reduced aggregate formation and decreased the number of TUNEL-labelled nuclei in skeletal muscle in an OPMD transgenic mouse model. Thus, anti-aggregation therapy may prove effective in the treatment of human OPMD. "

http://hmg.oxfordjou...nt/full/15/1/23


Haha, sorry to disappoint. Hm, it is interesting stuff. It's too bad they only devoted one figure to the mice as far as I could tell, and didn't really look at the amount of trehalose that was staying in their system (unless I missed that part).

FunkOdyssey does make a good point about the conversion to glucose, in the sense that when you take a ton of trehalose, you're also taking a ton of glucose. Then again, the soda I like to drink has 40 blood grams of sugar a can, and the stuff here suggests taking only 10 grams of trehalose, so you definitely won't be over hopping yourself up on glucose...

Sounds like a fair replacement to me :)



If you look at blood glucose levels and insulin after ingestion, Trehalose is not bad at all, it's a "good" sugar:

http://www.springerl...ee7em9u8ddn09g/

"Plasma glucose concentration 15 min postprandial was significantly higher in GLU compared to GAL and TRE (P<0.05). This was accompanied by a more than twofold greater rise in plasma insulin concentration in GLU compared to GAL and TRE (118% and 145%, respectively). "

Trehalose supplementation resulted in a much steadier blood-sugar level as compared to glucose.

#22 geddarkstorm

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Posted 17 December 2008 - 10:11 PM

If you look at blood glucose levels and insulin after ingestion, Trehalose is not bad at all, it's a "good" sugar:

http://www.springerl...ee7em9u8ddn09g/

"Plasma glucose concentration 15 min postprandial was significantly higher in GLU compared to GAL and TRE (P<0.05). This was accompanied by a more than twofold greater rise in plasma insulin concentration in GLU compared to GAL and TRE (118% and 145%, respectively). "

Trehalose supplementation resulted in a much steadier blood-sugar level as compared to glucose.



Which makes a lot of sense, as it has to be converted over time into glucose, rather than taking direct glucose. Good stuff, thanks for the links. Sounds like a winner in that regard, ontop of the putative autophagy and known dessication resistance.

Edited by geddarkstorm, 17 December 2008 - 10:14 PM.


#23 caston

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Posted 18 December 2008 - 12:05 AM

Does Trehalose taste sweet then?

Looks like it does...
http://en.wikipedia....i/Trehalose#Use

just wondering what would happen if we started making all the things that contain sugar (e.g. donuts, cakes, softdrinks) and used trehalose...

Edited by caston, 18 December 2008 - 12:10 AM.


#24 Shepard

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Posted 18 December 2008 - 12:17 AM

just wondering what would happen if we started making all the things that contain sugar (e.g. donuts, cakes, softdrinks) and used trehalose...


It wouldn't taste as good.

#25 StrangeAeons

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Posted 18 December 2008 - 04:31 AM

also less commercially viable, due to a significant increase in weight and volume. I've taken glycine before as a supplement, and though it tastes sweet it's more of a sickly sweet, I almost puked after taking a high dose and I have an iron stomach. Plus, put the stuff in candy bars and your average diabetic having an emergency (9/10 diabetic emergencies are hypoglycemia) reaches for one and ends up crashing because of the delayed glucose bump.

#26 100YearsToGo

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Posted 18 December 2008 - 01:52 PM

also less commercially viable, due to a significant increase in weight and volume. I've taken glycine before as a supplement, and though it tastes sweet it's more of a sickly sweet, I almost puked after taking a high dose and I have an iron stomach. Plus, put the stuff in candy bars and your average diabetic having an emergency (9/10 diabetic emergencies are hypoglycemia) reaches for one and ends up crashing because of the delayed glucose bump.


I don't like this bashing of trehalose ;) so lets put something straight;

Trehalose tastes just like sugar. I'm sure if you give it to someone in their coffee or tea they won't notice the difference. You can use it to bake everything you want but don't try to caramelize it. It is really cool stuff because it won't participate in malliard reactions. This is healthy, it won't hydrolyze and bind to amino acids and proteins. Foods (cookies anyone?) that depend on maillard reactions (browning) for their taste may suffer because of this. In baked goods it will inhibit starch retrogradation. It is extremely stable much more than glucose. It will protect food that is freezed or dried. Do I need to go on? :-D

#27 FunkOdyssey

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Posted 18 December 2008 - 04:26 PM

How exactly does trehalose induce autophagy? Does it act as a chaperone in chaperone-mediated autophagy by docking damaged proteins to the lysozome? It doesn't mess with mTOR, so what does it do?

Anyway, I ordered some to put in my tea. Doesn't seem like it could hurt.

#28 100YearsToGo

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Posted 18 December 2008 - 04:59 PM

How exactly does trehalose induce autophagy? Does it act as a chaperone in chaperone-mediated autophagy by docking damaged proteins to the lysozome? It doesn't mess with mTOR, so what does it do?

Anyway, I ordered some to put in my tea. Doesn't seem like it could hurt.


From the Rubinsstein study:

Small molecule enhancers of autophagy for neurodegenerative diseases
Sovan Sarkar* and David C. Rubinsztein*

"Trehalose has been termed as 'chemical chaperone' as it influences protein folding through direct protein–trehalose interactions, and thus it protects cells against various environmental stresses by preventing protein denaturation.48,49 It inhibits amyloid formation of insulin in vitro,50 and has been recently shown to prevent aggregation of beta-amyloid (Ab) associated with Alzheimer's disease. 51 Trehalose has also been shown to alleviate polyQ-induced pathology inHD mouse model, and this protective effect was suggested to be mediated by trehalose binding to the expanded polyQs, thus stabilizing the partially unfolded mutant protein.52 We have recently shown a novel property of trehalose in inducing mTORindependent autophagy. Trehalose enhanced the clearance of mutant huntingtin (and of A53T and A30P mutants of asynuclein), thereby reducing mutant huntingtin aggregation/toxicity.53 Trehalose treatment increased autophagic flux in avariety of mammalian cells, and we showed that these effects were mediated by intracellular trehalose.53"

Trehalose induces autophagy in a similar way as lithium. The following figure gives more detail:

Attached File  autophagy.JPG   38.91KB   64 downloads


Edited by 100YearsToGo, 18 December 2008 - 05:13 PM.


#29 FunkOdyssey

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Posted 18 December 2008 - 05:03 PM

That doesn't answer my question (that is some good information though). Rapamycin induces autophagy through mTOR, lithium induces autophagy by reducing inositol levels which leads to less calcium influx which somehow stimulates autophagy. The paper states that trehalose induces autophagy through an mTOR independent mechanism which means that it does not act similarly to rapamycin. I want to know how it works.

Edited by FunkOdyssey, 18 December 2008 - 05:04 PM.


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#30 100YearsToGo

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Posted 18 December 2008 - 05:14 PM

That doesn't answer my question (that is some good information though). Rapamycin induces autophagy through mTOR, lithium induces autophagy by reducing inositol levels which leads to less calcium influx which somehow stimulates autophagy. The paper states that trehalose induces autophagy through an mTOR independent mechanism which means that it does not act similarly to rapamycin. I want to know how it works.


My bad lithium.




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