LONGECITY

I came across this study from the Journal Nature Scientific Reports. 

 "Can the process of aging be delayed or even reversed? Research has shown that, in human cell lines at least, it can. They also found that the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging."

"These findings reveal that, contrary to the mitochondrial theory of aging, epigenetic regulation controls age-associated respiration defects in human fibroblast cell lines. Can epigenetic regulation also control aging in humans? That theory remains to be tested, and if proven, could result in glycine supplements giving our older population a new lease of life".

 

.http://www.scienceda...50526085138.htm

When I looked at glycine I was able to find lots of interesting studies about glycine.

http://www.ncbi.nlm....pubmed/24658997

http://valtsus.blogs...12/glycine.html

http://www.ncbi.nlm....pubmed/21795440

http://www.fasebj.or...Abstracts/528.2

Any thoughts on Glycine supplementation? It has the added advantage of being cheap.

Maybe, maybe not.

 

It has long been very obvious that mito dysfunction in the elderly is hardly at all caused by mutations (since they are too rare) and rather, by elimination, almost entirely by “deliberate” (i.e. regulated) nuclear gene expression changes, occurring as an adaptation to other things that are going wrong. That’s not to say that mito mutations are harmless though, not at all - but that their harm is via other means, such as my “reductive hotspot hypothesis” from 1998.

There is one interesting result in the paper, namely that glycine supplementation partly rejuvenates mito function - but I don’t think the authors believe that the result is robust, because they have relegated it to one sentence at the end of the results and one supplementary figure.

Posted by: Aubrey de Grey at May 27, 2015 6:31 AM

https://www.fightagi...ng.php#comments

5 to 8 grams a day is considered very safe and the cost is small so I will give it a try. 

I was considering buying some glycine for my father because studies have shown it to be beneficial to schizophrenics; but this was using ~50g of glycine per day. So I decided it wasn't worth the trouble.

I take almost 20 grams every night.   I started taking it to increase my growth hormone. but continued because the sleep is so good, very deep sleep.  Glycine sooths and relaxes.  I get 9-10 hours of sleep, good relaxing sleep.  I think my cortisol levels must have lowered.   18 grams of gelatine mixed into  14 ounces of boiling tap water.    (A stronger mixture makes a sticky gummy cleanup.   A tea bag and 1/2 tsp of honey for flavor.   Two ice cubes cool the tea so I can drink it quickly.

I take almost 20 grams every night.   I started taking it to increase my growth hormone. but continued because the sleep is so good, very deep sleep.  Glycine sooths and relaxes.  I get 9-10 hours of sleep, good relaxing sleep.  I think my cortisol levels must have lowered.   18 grams of gelatine mixed into  14 ounces of boiling tap water.    (A stronger mixture makes a sticky gummy cleanup.   A tea bag and 1/2 tsp of honey for flavor.   Two ice cubes cool the tea so I can drink it quickly.

18 grams of gelatin gives you less than 4 grams of glycine. Since glycine is sweet and without an objectionable taste, it can be added into fruit juice in much larger quantities.

Maybe, maybe not.

 

 

It has long been very obvious that mito dysfunction in the elderly is hardly at all caused by mutations (since they are too rare) and rather, by elimination, almost entirely by “deliberate” (i.e. regulated) nuclear gene expression changes, occurring as an adaptation to other things that are going wrong. That’s not to say that mito mutations are harmless though, not at all - but that their harm is via other means, such as my “reductive hotspot hypothesis” from 1998.

There is one interesting result in the paper, namely that glycine supplementation partly rejuvenates mito function - but I don’t think the authors believe that the result is robust, because they have relegated it to one sentence at the end of the results and one supplementary figure.

Posted by: Aubrey de Grey at May 27, 2015 6:31 AM

https://www.fightagi...ng.php#comments

Just a side note and not aim to divert this discussion. I was reading FA for quite some time, however it is very biased towards SENS. I do not want to say that they do not do good work, or I do not support them (I even donate small sums once in a while), however they have holes in their "theory" and lately the "programmed aging" scored quite a lot with real studies. Even in this case, this study asks SENS for realistically reviewing at least one of their "seven pillars". Anyway, FA is minimizing all the findings that are not within SENS line of work, and put them in a "doubt casting" light. Which I think, is far from being a good attitude in this "reverse aging" field, where we have to keep our minds open and be amazed by any new serious finding. If you look are the questions there, Reason/de Grey both avoid certain questions and answer just to whatever is favoring their view. I think that attitude is not ok, and that a more moderate - and accepting facts from all sides - attitude is required.

Most likely "aging" is dynamic, like Michael Fossel said, with "faces" that changes a lot and when you are sure that next step you have to look for something, bang, things change a lot. It is like in physics, "wave-corpuscule duality" - when you look for one, you run into the other one. Same here, probably both "programmed" and "wear-and-tear" are melt together but SENS/FA favor only one side and ignore anything else. And that attitude, I'm affraid, will bring them to a dead end.
 

 

I take almost 20 grams every night.   I started taking it to increase my growth hormone. but continued because the sleep is so good, very deep sleep.  Glycine sooths and relaxes.  I get 9-10 hours of sleep, good relaxing sleep.  I think my cortisol levels must have lowered.   18 grams of gelatine mixed into  14 ounces of boiling tap water.    (A stronger mixture makes a sticky gummy cleanup.   A tea bag and 1/2 tsp of honey for flavor.   Two ice cubes cool the tea so I can drink it quickly.

 

 

18 grams of gelatin gives you less than 4 grams of glycine. Since glycine is sweet and without an objectionable taste, it can be added into fruit juice in much larger quantities.

 

Gelatin is hydrolyzed collagen scraped from hides and other stuff.  The taste is neutral at best, but  sometimes a hide flavor.   Thanks for the advice, I will buy my extra glycine straight and sweet. 

 

Maybe, maybe not.

 

 

It has long been very obvious that mito dysfunction in the elderly is hardly at all caused by mutations (since they are too rare) and rather, by elimination, almost entirely by “deliberate” (i.e. regulated) nuclear gene expression changes, occurring as an adaptation to other things that are going wrong. That’s not to say that mito mutations are harmless though, not at all - but that their harm is via other means, such as my “reductive hotspot hypothesis” from 1998.

There is one interesting result in the paper, namely that glycine supplementation partly rejuvenates mito function - but I don’t think the authors believe that the result is robust, because they have relegated it to one sentence at the end of the results and one supplementary figure.

Posted by: Aubrey de Grey at May 27, 2015 6:31 AM

https://www.fightagi...ng.php#comments

 

Just a side note and not aim to divert this discussion. I was reading FA for quite some time, however it is very biased towards SENS. I do not want to say that they do not do good work, or I do not support them (I even donate small sums once in a while), however they have holes in their "theory" and lately the "programmed aging" scored quite a lot with real studies. Even in this case, this study asks SENS for realistically reviewing at least one of their "seven pillars". Anyway, FA is minimizing all the findings that are not within SENS line of work, and put them in a "doubt casting" light. Which I think, is far from being a good attitude in this "reverse aging" field, where we have to keep our minds open and be amazed by any new serious finding. If you look are the questions there, Reason/de Grey both avoid certain questions and answer just to whatever is favoring their view. I think that attitude is not ok, and that a more moderate - and accepting facts from all sides - attitude is required.

 

Most likely "aging" is dynamic, like Michael Fossel said, with "faces" that changes a lot and when you are sure that next step you have to look for something, bang, things change a lot. It is like in physics, "wave-corpuscule duality" - when you look for one, you run into the other one. Same here, probably both "programmed" and "wear-and-tear" are melt together but SENS/FA favor only one side and ignore anything else. And that attitude, I'm affraid, will bring them to a dead end.
 

 

But his point, that the reserachers were not  gorging their faces with Glycine, is valid isn't it?

I'm fond of FA, the point seems pretty valid regarding supplements: It is possible to spend decades of manhours and billions of dollars (reservatrol) and get nothing at all in return. Make the same investment with regards to Glucosephane and we would be there already perhaps.

Does not mean I won't experiment with what supps are out there right now though.

glycine stimulates production of Growth Hormone.... Having more Growth Hormone is always a bad thing in my book.. So no thanks! 

Just a side note and not aim to divert this discussion. I was reading FA for quite some time, however it is very biased towards SENS. I do not want to say that they do not do good work, or I do not support them (I even donate small sums once in a while), however they have holes in their "theory" and lately the "programmed aging" scored quite a lot with real studies. Even in this case, this study asks SENS for realistically reviewing at least one of their "seven pillars". Anyway, FA is minimizing all the findings that are not within SENS line of work, and put them in a "doubt casting" light. Which I think, is far from being a good attitude in this "reverse aging" field, where we have to keep our minds open and be amazed by any new serious finding. If you look are the questions there, Reason/de Grey both avoid certain questions and answer just to whatever is favoring their view. I think that attitude is not ok, and that a more moderate - and accepting facts from all sides - attitude is required.

 

Most likely "aging" is dynamic, like Michael Fossel said, with "faces" that changes a lot and when you are sure that next step you have to look for something, bang, things change a lot. It is like in physics, "wave-corpuscule duality" - when you look for one, you run into the other one. Same here, probably both "programmed" and "wear-and-tear" are melt together but SENS/FA favor only one side and ignore anything else. And that attitude, I'm affraid, will bring them to a dead end.

The paper that brought this thread about probably isn't the best evidence for the programmed aging viewpoint, but given all the community agreement with this post, it's clear that people think FA is too deeply in the bag with the SENS model.  I think that Reason is putting his efforts where he believes they will do the most good.  It's pretty clear that there are paracrine signaling molecules that affect many and various systems, and lead to at least part of the aging phenotype.  Imagine for a moment that we had a mechanism to reverse all that signaling, returning it to a youthful profile.  All or most of the SENS types of damage would still be there, and would still need to be fixed.  For all we know, that damage is the very reason for the changes in paracrine signaling that people sometimes call "programmed aging".  

In its most extreme form, "programmed aging" is claimed to be an evolved system, brought about through group selection, driven by an enhanced level of group fitness resulting from not having all those old folks sitting around eating up all the food and taking up valuable space.   This ignores the fact that predation and infection is rampant in nature, thus animals have never needed any help in order to die.  In those relatively few cases where predation is not so much of a problem, what do we find in nature?  Not programmed aging-- those animals live much longer than more highly predated species.  Thus the idea of an evolved aging program is completely at odds with what we observe in nature. 

Changes in paracrine signaling, if not due to damage, might instead be due to an uncontrolled running-on of developmental programs.  If this is the case, it is something that we will need to address, but it's not the only thing we'll need to address.  There is still going to be plenty of damage that needs to be repaired.   If Reason and Aubrey are missing (or more likely choosing not to focus on) a part of the aging puzzle, I'm not worried:   There are far too few people working on damage repair, and there doesn't seem to be a shortage of people working on signaling.   I don't feel like there are excessive resources being allocated to damage repair.  On the contrary, I'd like to see more.  I'd also like to see more resources going into signalling, but that money comes from conventional sources, while SENS money does not.  As such, the efforts of SRF are not taking resources away from the signalling crowd.   Considering all of this, I think that Reason and SRF's focus on damage repair is both non-harmful and likely to be helpful.

 

The paper that brought this thread about probably isn't the best evidence for the programmed aging viewpoint, but given all the community agreement with this post, it's clear that people think FA is too deeply in the bag with the SENS model.  I think that Reason is putting his efforts where he believes they will do the most good.  It's pretty clear that there are paracrine signaling molecules that affect many and various systems, and lead to at least part of the aging phenotype.  Imagine for a moment that we had a mechanism to reverse all that signaling, returning it to a youthful profile.  All or most of the SENS types of damage would still be there, and would still need to be fixed.  For all we know, that damage is the very reason for the changes in paracrine signaling that people sometimes call "programmed aging".  

 

In its most extreme form, "programmed aging" is claimed to be an evolved system, brought about through group selection, driven by an enhanced level of group fitness resulting from not having all those old folks sitting around eating up all the food and taking up valuable space.   This ignores the fact that predation and infection is rampant in nature, thus animals have never needed any help in order to die.  In those relatively few cases where predation is not so much of a problem, what do we find in nature?  Not programmed aging-- those animals live much longer than more highly predated species.  Thus the idea of an evolved aging program is completely at odds with what we observe in nature. 

 

Changes in paracrine signaling, if not due to damage, might instead be due to an uncontrolled running-on of developmental programs.  If this is the case, it is something that we will need to address, but it's not the only thing we'll need to address.  There is still going to be plenty of damage that needs to be repaired.   If Reason and Aubrey are missing (or more likely choosing not to focus on) a part of the aging puzzle, I'm not worried:   There are far too few people working on damage repair, and there doesn't seem to be a shortage of people working on signaling.   I don't feel like there are excessive resources being allocated to damage repair.  On the contrary, I'd like to see more.  I'd also like to see more resources going into signalling, but that money comes from conventional sources, while SENS money does not.  As such, the efforts of SRF are not taking resources away from the signalling crowd.   Considering all of this, I think that Reason and SRF's focus on damage repair is both non-harmful and likely to be helpful.

 

@ Niner -

1. I'm not in the medical or biological field. Though I have a lot of very close family and friends that are ... including my wife that is a MD and happend to be a very smart and skilled one - and she is hammering me with counterarguments at most of my rejuvenation/reverse aging stuff ... so I have to learn lots of things in this field. However my logical system was developed under other science fields and I use that "tool" a lot in my research. So I see things a bit different then most of you. Anyway, do not get me wrong, I do not want to start a war of arguments but your logic has lost of flaws. Here comes first:

"Imagine for a moment that we had a mechanism to reverse all that signaling, returning it to a youthful profile.  All or most of the SENS types of damage would still be there, and would still need to be fixed." - NO if I can reprogram humans (and I hope pets too!) to be @ biological age of 18 all that damage is not "identifiable" neither creating real problems - unless suffering from something like genetic disorders or other illnesses that btw others in this field are working harder to solve. And some of these teams are more advanced in their research then SENS.

Then once I reprogram somebody to be 18 biological age, in five or three years re-do the process and become 18 again ... keep on doing it. Do you see where it goes? No much need for something else ... that damage you are talking about, is there, but I trick my body to be 18 again and there are not many problems.

2. "Not programmed aging-- those animals live much longer than more highly predated species.  Thus the idea of an evolved aging program is completely at odds with what we observe in nature." - not really! In fact that even we are capable to fend off all "damages" we are still on the path of "the program" and age and die. Have you heard of the "tunnel effect" in physics? Same thing could happen here. Few persons, animals, etc can "penetrate" and fend off all the damage and live for a lot longer than others. And when I say longer I mean by centuries/milleniums. AFAIK did not see that, meaning something is "after us", something is programmed inside. So even you fend off all those asteroids in space, your ship is destined to selfdestroy once you deiver the payload. If I want to be "aggresive" I can spend time in doing a probabilistic calculation and prove mathematical wrong the "damage" theory. Damage, yes cause problems and those problems increase as we get old as the entropy of our sistem (=body) grows. Yet there are ways we can reduce or reverse some of that dissorder by interviening in certain places. Anyway, my point is NOT to show one theory is bad and the other is good - my point is that we need to look at things from a much larger perspective and consider seriously anything that comes from good studies. If something hit my approach, I need to accept that data and incorporate it in my work, then go back to drafting board and re-design the ship to sustain the new challange. We need to incorporate all the facts and create a common front, but not disregarding others, especially that they scored big lately through studies.

3. "  If Reason and Aubrey are missing (or more likely choosing not to focus on) a part of the aging puzzle, I'm not worried:" - sorry, but this is science, you cannot avoid, hide or ignore some results just because they are not on your line of thought. This is not a discussion in the Academy/Agora. We want to solve aging or not? I cannot just discuss what I want/like, we have to solve things as they come. In this particular case, SENS/FA needs to man up and accept the issue and address it appropriately, not hiding it under carpet. That is the attitude we want.

BTW things update "by hour" in this field, and sorry to say but if you lay out a research path a decade ago and believe that "nothing" has changed or not need to be revised, that sound more like a "prophecy" to me than real science. And we know from history what happen when church's dogma interfered with scientists.

Real science is hard and tough, comes in strange chunks and from various directions. Hug one single theory and you will fail. Keep your mind open, and learn to wonder at new things and you will be on the right path. That is why even geniuses like Einstein failed. He developed Special Relativity and "felt in love" with that theory, but second time around with the General Relativity, things didn't pan out. And that is because he wanted to "model" the universe around his first theory, but the Universe is a wild animal. I do belive an attitude like Feynman's is more appropriate.

Anyway, sorry to sink your ships, I did not plan that, but your logic has many issues ...

But to finish: I do not want to continue arguing and counter-arguing, because I can use math to prove things, however I would like to see a more moderate and open mind attitude from them and a more pragmatical one. Understand that we are all looking for a real solution for reverse aging, and I care less if it is "programmed" or "wear and tear", or whatever. I want like a common front and I do want SENS/FA to accept that things need to be upgraded (sometimes at an interval of days), and be more flexible in their approach.

Make SENSe?

 

Heyas, im a new guy. Just wanted to post this, as i dont think anyone else has yet. It looks like glycine might be semi-essential.

http://www.ncbi.nlm....pubmed/20093739

I must admit I am a little confused by L-Glycine because I was under the impression that its metabolism would would actually result in a reduction of NAD+ and that seems at odds with results. I am guessing that perhaps I just misunderstood what I have read? Also wouldn't you have to be somewhat careful combining high amounts of Glycine supplementation with a ketogenic diet? I believe I read that can be fairly dangerous if you have certain gene mutations because if drastically increased possibility of ketoacidosis.

Clearly I need to research this more and get a better understanding of it.

Heyas, im a new guy. Just wanted to post this, as i dont think anyone else has yet. It looks like glycine might be semi-essential.

A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.

http://www.ncbi.nlm....pubmed/20093739

Interesting. Might be useful for tendinosis?

 

Heyas, im a new guy. Just wanted to post this, as i dont think anyone else has yet. It looks like glycine might be semi-essential.

A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.

http://www.ncbi.nlm....pubmed/20093739

 

Interesting. Might be useful for tendinosis?

 

There is a study for that: 

The presence of metalloproteinase-2 indicates that a tissue is undergoing a remodeling process. High birefringence suggests a better organization of collagen bundles. After 21 days, G5 sustained a high load before rupture, unlike G4. The results suggest that GT + a glycine diet has beneficial effects that aid in the recovery process of the tendon after tendinitis.

http://www.ncbi.nlm....pubmed/25360832

I wonder if it would help to prevent tendonosis or other injuries as well. Because that study makes it sound like most people arnt getting anywhere near enough.

anyone have access to this study? it would be interesting to see what happened. http://www.ncbi.nlm....pubmed/14366297

This rat study is interesting

http://link.springer...0726-012-1422-8

as is this

http://openheart.bmj.../1/e000103.full

...as is this
http://openheart.bmj.../1/e000103.full

Found this comment on GRG the other day:

 

This study is complete garbage - they used cell lines instead of tissue homogenates for sequencing. There is age-related accumulation of mtDNA mutations in human tissues, confirmed in many locations and in multiple studies, so if you look at your material and fail to find them, you should discard the material rather than waste other people's time with your conclusions.

More junk medical science? (well over 50% of studies cannot be reproduced)

The comment was made by Rafal Smigrodzki, who is working with SENS:

http://www.sens.org/...ging-conference

so he is very upset (along with de Grey) about the outcomes of this study that contradicts their hypothesis. And that is understandable, however is much better if they try to

understand WHY this result and plug it in their theory and evolve from there, instead of having this nervous reaction. It is much more beneficial for  the entire rejuvenation community to

work this way.

However the study done by Japanese cannot be counteracted by a comment "This study is complete garbage - they used cell lines instead of tissue homogenates for sequencing."

Have SENS and others tried to reproduce it and failed?

Until real studies in HUMANS done by SENS come out, we need to refrain on extra-commenting. At least the Japanese team used "human fibroblast lines derived from elderly subjects" rather than mice studies.

sorry, just wondering what GRG is? :]

@ aza - Gerontology Research Group

it has a moderated discussion list, if you want to join it, you have to submit a request.

There are lots of nice contributors.

here is the web site:

http://www.grg.org/

I bought 1 lb of NOW FOODS glycine powder @ $13.92 FS from PureFormulas.com

to see if it would help with my achilles tendinitis.

I have been taking 16 grams/day starting last week. Is this enough?

8 grams in my morning coffee, in place of sugar. OK taste.

8 grams in cup of warm water at night. OK taste.

I tried 8 grams in my evening caipirinha cocktail, but it was not sweet enough to

out compete the lime juice.  Glycine has been reported to improve alcohol

induced liver problems, so that is a plus for us drinkers.

So far my achilles is fine even though I am increasing my running distance.

My achilles problem has been chronic over many years.  Every few months it

become irritated and I have to baby it for a few weeks, before I start running

again.

I do not notice any effect other than possibly waking up rested earlier in the morning than usual.  No mood changes obvious.

No increased longevity yet.  No improvement in my tennis game.

Health Stats: 70yo, 6ft, 179lb, very active.

I think 5-10 g glycine (or 10-30 g gelatin for omnivores) is a good idea: I take 1 tsp glycine in the evening as sweetener in hibiscus tea. 

It's cheap and harmless even at high doses:

Inagawa K et al. 2009. Assessment of acute adverse events of glycine ingestion at a high dose in human volunteers Journal of Urban Living and Health Association Vol. 50 No. 1 P 27-32

Glycine may be a semi-essential amino acid in humans:

Meléndez-Hevia E & de Paz-Lugo P. 2008. Branch-point stoichiometry can generate weak links in metabolism: the case of glycine biosynthesis. Journal of biosciences, 33(5), 771-780.

Meléndez-Hevia E et al. 2009. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. Journal of biosciences, 34(6), 853-872.

The best evidence for common glycine deficiencies is pyroglutamic acid in urine among populations consuming little connective tissue / collagen / gelatin:

Jackson AA et al. 1996. Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased in normal adults consuming vegetarian or low protein diets. The Journal of nutrition, 126(11), 2813-2822.

Lenton C et al. 1998. Infants in Trinidad excrete more 5-L-oxoproline (L-pyroglutamic acid) in urine than infants in England: an environmental not ethnic difference. British Journal of Nutrition,80(01), 51-55.

Indeed, glycine insufficiency may be the most immediately harmful aspect of low protein diets:

Jackson AA et al 2002. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clinical Science, 103(6), 633-639.

Brawley L et al. 2004. Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy. The Journal of physiology, 554(2), 497-504.

There's substantial evidence supplemental glycine improves sleep in humans:

Inagawa K. et al. 2006. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms, 4(1), 75-77.

Yamadera W et al. 2007. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological rhythms, 5(2), 126-131.

Bannai M & Kawai, N. 2012. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. Journal of pharmacological sciences, 118(2), 145-148.

Bannai M et al. 2012. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in neurology, 3.

In animal studies, glycine is broadly cytoprotective:

Weinberg JM et al. 1987. Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules.Journal of Clinical Investigation, 80(5), 1446.

Yin M et al. 1998. Glycine accelerates recovery from alcohol-induced liver injury. Journal of Pharmacology and Experimental Therapeutics, 286(2), 1014-1019.

Gusev EI.et al. 2000. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Cerebrovascular Diseases, 10(1), 49-60.

Senthilkumar R et al. 2003. Glycine modulates hepatic lipid accumulation in alcohol-induced liver injury. Pol J Pharmacol,55(4), 603-611.

Qi RB et al. 2007. Glycine receptors contribute to cytoprotection of glycine in myocardial cells.Chinese Medical Journal, 120(10), 915.

Mikalauskas S et al. 2011. Dietary glycine protects from chemotherapy-induced hepatotoxicity. Amino acids, 40(4), 1139-1150.

Petrat F et al. 2011. Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine. European Surgical Research, 46(4), 180-187.

Petrat F et al. 2012. Glycine, a simple physiological compound protecting by yet puzzling mechanism (s) against ischaemia–reperfusion injury: current knowledge. British journal of pharmacology, 165(7), 2059-2072.

Barakat HA & Hamza AH 2012. Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats. Eur Rev Med Pharmacol Sci,16(6), 728-736.

Ruiz-Ramirez A et al 2014. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clinical Science, 126(1), 19-29.

This is partly mediated by glycine's anti-inflammatory effects:

Wheeler MD & Thurman RG 1999. Production of superoxide and TNF-α from alveolar macrophages is blunted by glycine. American Journal of Physiology-Lung Cellular and Molecular Physiology, 277(5), L952-L959.

Wheeler MD et al. 2000. Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279(2), L390-L398.

Wheeler MD et al. 2000.  Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production. The FASEB Journal, 14(3), 476-484.

Mauriz JL et al. 2001. Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat. Free Radical Biology and Medicine, 31(10), 1236-1244.

Li X et al. 2001. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Infection and immunity, 69(9), 5883-5891.

Tsune I et al. 2003. Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology, 125(3), 775-785.

Bruck R et al. 2003. Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice. Liver international, 23(4), 276-282.

Meza DL et al 2006. Effect of glycine in the immune response of the experimentally diabetic rats. Revista Alergia México, 53(6), 212.

Yamanouchi K et al. 2007. Glycine reduces hepatic warm ischaemia–reperfusion injury by suppressing inflammatory reactions in rats. Liver International, 27(9), 1249-1254.

Garcia-Macedo R et al. 2008. Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cells. European journal of pharmacology, 587(1), 317-321.

Alarcon-Aguilar FJ et al 2008. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.European journal of pharmacology, 599(1), 152-158.

Wang HD et al 2009. Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFα production in cardiomyocytes by activating a glycine receptor. Acta Pharmacologica Sinica, 30(8), 1107-1114.

Almanza-Perez JC 2010. Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2. Biomedicine & Pharmacotherapy, 64(8), 534-540.

Bruns H. et al. 2011. Glycine and taurine equally prevent fatty livers from Kupffer cell-dependent injury: an in vivo microscopy study. Microcirculation (New York, NY: 1994), 18(3), 205.

Ceyhan G O et al. 2011. Prophylactic glycine administration attenuates pancreatic damage and inflammation in experimental acute pancreatitis. Pancreatology, 11(1), 57-67.

Hasegawa S et al. 2012. Cysteine, histidine and glycine exhibit anti‐inflammatory effects in human coronary arterial endothelial cells. Clinical & Experimental Immunology, 167(2), 269-274.

Wu HW et al 2012. Effects of glycine on phagocytosis and secretion by Kupffer cells in vitro. World journal of gastroenterology: WJG, 18(20), 2576.

Vieira CP et al. 2015. Glycine improves biochemical and biomechanical properties following inflammation of the Achilles tendon. The Anatomical Record, 298(3), 538-545.

The anti-inflammatory effect of glycine may also account for tumor growth retardation:

Rose ML et al. 1999. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis,20(5), 793-798.

Rose, ML et al. 1999. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Carcinogenesis, 20(11), 2075-2081.

Amin K et al. 2003. Dietary glycine inhibits angiogenesis during wound healing and tumor growth. Cancer biology & therapy, 2(2), 173-178.

Yamashina S et al. 2007. Glycine as a potent anti‐angiogenic nutrient for tumor growth. Journal of gastroenterology and hepatology, 22(s1), S62-S64.

Glycine prevents glycation driven cataracts:

Ramakrishnan S & Sulochana KN. 1993. Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. Experimental eye research, 57(5), 623-628.

Alvarado-Vásquez N. et al 2006. Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats. Life sciences,79(3), 225-232.

Bahmani F et al. 2012. Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Molecular vision, 18, 439.

And perhaps of most interest on this board, glycine supplementation appears to mimic methionine restriction, with clearance of excess methionine via glycine N-methyltransferase.

Benevenga NJ & Harper AE. 1967. Alleviation of methionine and homocystine toxicity in the rat. The Journal of nutrition 93.1: 44-52.

Peng YS et al. 1981. Alleviation of methionine toxicity by glycine and serine in rats pretreated with excess retinol. Nutrition Reports International.

Sugiyama K et al. 1987. Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. Journal of nutritional science and vitaminology, 33(3), 195-205.

Rowling MJ et al. 2002. Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine in rats. The Journal of nutrition, 132(9), 2545-2550.

Luka Z et al 2002). Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Human genetics, 110(1), 68-74.

Fukada SI et al 2006. Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats.Bioscience, biotechnology, and biochemistry, 70(10), 2403-2409.

Fukada SI et al 2008. Effects of various amino acids on methionine-induced hyperhomocysteinemia in rats. Bioscience, biotechnology, and biochemistry, 72(7), 1940-1943.

Brind J et al. 2011. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. The FASEB Journal, 25(1_MeetingAbstracts), 528-2.

I cant help but wonder what the optimal methionine to glycine ratio is. I personally was going to aim for 1:6, with around 13g of glycine a day. No clue if that is enough though.

It probably depends upon whether one's seeking reduced homocysteine, effective methionine restriction, or other benefits. In Fukada SI et al 2008, the control rats consumed 0.8% (wt/wt) Met diets, while those with experimental hyperhomocysteinemia consumed 1.8% Met, so between 0.8% and 1.8% (range likely depends on other amino acid intake), the ability to regulate Hcy was overwhelmed. Supplemental intake of 2.5% glycine or serine (beyond the 1.8% Gly + Ser in the base diet) largely eliminated the Hcy elevation. For supplementation to reduce Hcy, perhaps 2 or 3:1 supplemental glycine/excess dietary methionine (wt/wt) is a useful target. On the other hand, Brind J et al. 2011 found roughly 28% lifespan extension with 8% Gly in a 0.43% Met diet (18:1), but didn't think their 4% Gly diet (9:1) results were worth mentioning in their poster abstract.

My own decision to opt for 1 heaping tsp (~6 g) is influenced mostly by Meléndez-Hevia E et al. 2009, which calculated a daily glycine deficit of –8.5 to –10 g/day. My supplementation is in the context of a barely methionine adequate lower-protein vegan diet (I'd shift to higher protein if I were 65+ yo).

It probably depends upon whether one's seeking reduced homocysteine, effective methionine restriction, or other benefits. In Fukada SI et al 2008, the control rats consumed 0.8% (wt/wt) Met diets, while those with experimental hyperhomocysteinemia consumed 1.8% Met, so between 0.8% and 1.8% (range likely depends on other amino acid intake), the ability to regulate Hcy was overwhelmed. Supplemental intake of 2.5% glycine or serine (beyond the 1.8% Gly + Ser in the base diet) largely eliminated the Hcy elevation. For supplementation to reduce Hcy, perhaps 2 or 3:1 supplemental glycine/excess dietary methionine (wt/wt) is a useful target. On the other hand, Brind J et al. 2011 found roughly 28% lifespan extension with 8% Gly in a 0.43% Met diet (18:1), but didn't think their 4% Gly diet (9:1) results were worth mentioning in their poster abstract.

 

My own decision to opt for 1 heaping tsp (~6 g) is influenced mostly by Meléndez-Hevia E et al. 2009, which calculated a daily glycine deficit of –8.5 to –10 g/day. My supplementation is in the context of a barely methionine adequate lower-protein vegan diet (I'd shift to higher protein if I were 65+ yo).

Thank you Darryl for that post! Without it, this would not have clicked in my head!

I have come across some potentially important findings reported in a recent open access paper by Tang et al. (2015); covering the epigenetic effects of methionine restriction ("MR") and the amino acid response ("AAR"):

• Tang X, Keenan MM, Wu J, Lin C-A, Dubois L, Thompson JW, et al. (2015) Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis. PLoS Genet 11(4): e1005158. doi:10.1371/journal.pgen.1005158

So why is this relevant? Get ready! The researchers state that "simulatneous deprivation of methionine and [other] sources of creatine biosynthesis (either arginine or glycine)" (Tang et al. 2015), interferes with the MR mediated AAR. In case you're not familiar, the AAR is believed to be behind many of the key longevity and improved stress response pathways of MR. Have a gander at this other delicious open access journal for more info on that:

• Johnson JE, Johnson FB (2014) Methionine Restriction Activates the Retrograde Response and Confers Both Stress Tolerance and Lifespan Extension to Yeast, Mouse and Human Cells. PLoS ONE 9(5): e97729. doi:10.1371/journal.pone.0097729

Tang, X. et al. (2015) also note that deprivation of practically all amino acids, except for glycine initiates the AAR. So the evidence seems to indicate that glycine is not only ok for MR, but maybe necessary. To undertand why, read the paper by Tang, X. et al. (2015); the researchers note that when MR is initiated, the body uses up "S-Adenosyl-L-methionine (SAM)" reserves to biosynthesize creatine. This results in epigenetic modifications like reduced methylation and changes to gene transcription. Tang, X. et al. (2015) seem to show that these SAM reserves aren't used up when glycine or arginine are lacking. According to Darryl's post, glycine may not be abundant enough in a MR vegan diet.

Creatine on the other hand may now need to be reconsidered. Tang, X et al. (2015) seem to show that if creatine biosynthesis is not active, then MR cannot work. So should we be cutting out creatine supplementation and instead be using glycine? Further studies are warranted.

On a sidenote, I also want to point to these recent finding showing that the effects of ketogenic diets are also mediated largely by MR:

• Pavlos, P. et al. (2013). Methionine and choline regulate the metabolic phenotype of a ketogenic diet. Mol Metab.; 2(3): 306–313.

Not to derail the thread, but I want to delve deeper into this SAM depletion idea proposed by Tang, X. et al. (2015).

I wonder what effect folate (5MTF), b12 and b6 might have on MR and the AAR? Anyone want to chime in on whether they would interefere? I certainly hope homocysteine isn't also necessary for MR life-extension.

Yet another recent open access paper shows for the first time that the MR mediated AAR may negate the damaging effects of hyperhomocysteinemia, via FGF-21 and adiponectin secretion:

• Ables, G. et al. (2015). Dietary Methionine Restriction in Mice Elicits an Adaptive Cardiovascular Response to Hyperhomocysteinemia. Nature Scientific Reports; 5; Article number:8886.

So Ables, G et al. (2015) showed that old MR mice had increased homocysteine, but this was offset by the FGF-21 and adiponectin secretion. I wonder if glycine might mitigate homocysteine increases in such a scenario? I personally haven't seen evidence that folate, b12 and b6 interfere with MR, but they would help to recycle methioine correct?

On one hand glycine seems to help deplete SAM, while folate recycles it?

NAD+ repletion, in the form of higher dose vitamin b3 (I prefer nicotinamide) is also a methyl sink. I noticed in the Ables, G et al. (2015) study that adiponectin was elevated and the researchers noted that this was indicative of AMPK activity. I therefore would ask whether MR vegan diets could upregulate NAMPT via AMPK and allow for more effiicient use of nicotinamide. While proptection from homocysteine sounds good, I like to be on the safe side and take 400mcg folate (5mtf), 1000mcg b12 and 25mg b6 to keep homocysteine in check. I'm stumped on whether these vitamins could interfere with a MR vegan diet.

Taurine appears to be fine, wheras NAC may interfere:

• Elshorbagy, AK. (2013). Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance. Metabolism. 2013 Apr;62(4):509-17

Apparently MR vegans could be adipose (fat) resistant lol! I do know at least one fat vegan, although I'm conviced her excessive alcohol consumption has resulted in some form of metabolic syndrome... Anyone curious about how vegan diets mediate MR should read:

• McCarty, MF. et al. (2009). The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009 Feb;72(2):125-8.

My own n1 personal experience:

For the past two years I've been eating a low protein vegan diet and I am also a regular user of topical tazarotene. Last night I took 10g glycine before bed and applied tazarotene as usual. Upon waking up I discovered a very significant increase in skin exfoliation. I was worried for some time that I was not responding to tazarotene since I hardly ever peel following use. However what I saw this morning was dramatic, I didn't even know that my face was capable was shedding that much skin. 

My hypothesis is that glycine supplementation satisfied my skins requirement for collagen production. The paper by Meléndez-Hevia E et al. (2009), which Darryl referenced seems to support this.