Glycine supplementation could reverse aging

Aging means dysfunctional mitochondria

One of the hallmarks of aging is dysfunction in mitochondria, the powerhouses of the cell. Mitochondria have their own DNA, and the mitochondrial theory of aging posits that increased mutations in mitochondrial DNA cause this dysfunction.

A very neat piece of scientific research, published in Nature Scientific Reports, has now found that the respiratory defects in mitochondria are due not to mutations in mitochondrial DNA, but to epigenetic regulation, in other words, due to changes in gene expression.

The Japanese scientists doing the study found that reversing the epigenetic changes caused the mitochondria in cells from very old people, aged 80 to 97, basically to become like brand new mitochondria, with the functional capability of mitochondria from fetal cells. That’s a very good thing.

In searching for the genes that controlled mitochondrial respiration, they found two, and these two control glycine production in mitochondria. Glycine is a non-essential amino acid, also available as a cheap over-the-counter supplement.

When glycine was added to culture media containing cells from the 97-year-old, the mitochondria in these cells became like new.

This study suggests a number of things.

Aging may be programmed

One, it suggests that aging is programmed. Mitochondrial dysfunction with aging appears not to be a matter of accumulating mutations that the organism has no control over, but rather a controlled difference in gene expression, controlled by the organism itself. In other words, aging is not accumulation of random damage, but a programmed function.

This lends some evidence to my recent assertion that nature wants you to die, and that you must outwit nature to increase maximum lifespan.

Glycine supplementation increases lifespan in rats

Two, it suggests that glycine supplementation can fight aging, and indeed, in the experiment, it did, albeit in cell culture, not in vivo. It’s too early to say what the proper dose of glycine might be, but we can speculate that it would be enough to bring glycine levels up to those seen in young people. (Indeed, in infants.)

Very interestingly, we already know that, in rats, glycine supplementation increases lifespan, through increased clearance of methionine. (Glycine here acts as a methionine restriction mimetic.) The amount of glycine fed to those rats with increased lifespan was approximately 3 to 6 times the amount fed to controls, which is, I would say, a very doable proposition. A few grams of glycine daily might do the trick.

Worthy of note, increasing lifespan in rats is a much better indication of what might work in humans than increasing lifespan in C. elegans. Far fewer things work in increasing rodent lifespan than they do in nematodes.

Could the mechanism of the increased dietary glycine that caused greater lifespan be that it made the rats’ mitochondria more youthful? Yes, it very well could be. Methionine restriction causes much better mitochondrial function, so that’s probably what the glycine is doing, since increased glycine is a methionine restriction mimetic.

Three, and this is my own insight/speculation, glycine is probably increasing levels of glutathione in mitochondria, and since glutathione is the cells’ and the mitochondria’s main internal antioxidant, this protects them from oxidative damage and keeps them in a youthful state. Glutathione is made from three amino acids, one of which is glycine, and if glycine is in short supply inside the mitochondria, then there will be less glutathione there. Methionine restriction also increases mitochondrial glutathione levels.

Four, also my own (informed) speculation, one of the chief roles of autophagy is to turn over defective mitochondria, to allow the cell to replace them with new ones. So this study reaffirms the role of declining autophagy in aging.

Glycine supplementation could reverse aging

By the way, the authors of the paper themselves do not shy away from suggesting that glycine supplementation could decrease or reverse aging.

This is an exciting study and, although much more work will be needed, appears to open up a new avenue in potential anti-aging and life extension treatments. Best of all, glycine is cheap and likely very safe, since it’s an amino acid the body produces itself.

P.S.: My new book, Stop the Clock: The Optimal Anti-Aging Strategy will be out soon.

image_pdfimage_print

Leave a Comment:

24 comments
Chris says June 8, 2015

When you tweeted this study a week ago, I did some lazy research on my own (checked wikipedia sources) and then bought some. It’s only been a week but this is definitely staying stocked in my supplement drawer.

At first I followed this study: http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8425.2007.00262.x/abstract;jsessionid=C3F3A7872FBF3EC635D3E36E9642634B.f04t03

I took three grams at bedtime. I slept three hours (usual eight). I woke up with a significant but non-debilitating headache. That day I had a big boost in energy but at the same time was calmer and much more focused. The following days I switched to the bottle’s directions (now brand capsules) of one gram with a meal three times a day and that cut down on the headache but left the benefits intact. I still get a minor headache every time I take it but my productivity is up. I’ve been burning through my backlog of chores and errands all week. My sleep is down to about five hours but I don’t feel the slightest bit groggy or dull during the day. I actually feel much more alert than usual. I tend to be a jittery, restless person and I’ve had multiple people comment on how calm I look compared to normal.

A major caveat, I’m extremely sensitive to psychotropics. So if I had to guess this probably has more to do with its activity as a neurotransmitter than with mitochondria, but could be both. I don’t know what a normal person should expect in the short term but at least I found something that works for me. No sign of fading a week in. I hope it holds.

Reply
    P. D. Mangan says June 13, 2015

    Chris, I’ve been trying some glycine the last couple days. The company “Bulk Supplements” offered me a free supplement so I chose the glycine. I’ve taken about 2 grams each night before bed and I’m sorry to report… nothing happened with regard to sleep. I was hoping because I often have trouble sleeping, especially in the summer when it’s warm, but I can’t tell anything. I might need to increase the dose but 2 grams seems like something should be happening. Anti-aging effects take longer – the report cited above used 10 days in cell culture – so I’m not disappointed in that regard. Doesn’t mean I’ll necessarily feel that though.

    Reply
      Haven M. says June 16, 2015

      interesting. is that the recommended dosage then, 2g?

      Reply
        P. D. Mangan says June 16, 2015

        I’ve seen up to 3 g recommended for sleep.

        Reply
Chris says June 8, 2015

Just realized I forgot to say, Thank You!

Keep up the good work.

Reply
    P. D. Mangan says June 8, 2015

    Chris, thanks for your report. I also suspect that your effects may be more neurotransmitter oriented, but who knows. You didn’t state your age, and I suspect mitochondrial effects might be felt much more in older people – like me, heh. I may have to try this, although right now I’ve got a lot of supplements on my list. May have to do some triage.

    I’m happy you appreciate the blog.

    Reply
Lobo says June 9, 2015

So 3 grams a day? Or more?

How about regular intakes of bone broth to satisfy our glycine needs?

Reply
    P. D. Mangan says June 9, 2015

    I’m thinking that amount would be plenty. I’m afraid I don’t know how much is in bone broth though.

    Reply
      Rob H says January 24, 2016

      Hello Dennis, as per my previous comment, I’ve just started taking 3 or 4 grams of glycine powder per day – primarily for its methionine restriction mimetic effect. The instructions on the pack recommend taking the glycine powder pre-bedtime on an empty stomach. This makes sense as I have heard that glycine supplementation can improve sleep. However, since glycine is an amino acid, the big question is will it interfere with overnight autophagy? I’m assuming not since glycine doesn’t seem to have any anabolic properties as such?

      Moreover, it seems from your comment from yesterday that it may be better to take glycine AWAY from any proteins containing cysteine – since dietary cysteine will abrogate the methionine restriction effect of glycine. So again this would seem to indicate that taking glycine on an empty stomach (maybe with just a little fat) pre-bedtime is the preferred option?

      Reply
        P. D. Mangan says January 25, 2016

        Hi Rob, when I was taking glycine (which I should start doing again) I took it at night before bed for its effects on sleep. Unfortunately, I never felt such effects and it didn’t improve my sleep. Could be that I wasn’t taking enough, I believe I took about 2 grams.

        Leucine is the amino acid that appears to regulate autophagy, but I’ve always been careful about others, such as cysteine and glycine, for their possible ability to do so. Amino acids are protein constituents after all, and protein abolished autophagy. That being said, I don’t know that glycine would affect autophagy, and very likely does not. If it did, we probably wouldn’t see those robust methionine restriction effects.

        So I’d say that taking glycine at night is fine.

        Reply
          Rob H says January 25, 2016

          Hi Dennis – many thanks as ever for the considered response to my question. I was hoping you’d say that! I figured that since glycine is a non-essential amino acid, it’s not like I would be exogenously supplying the body with anything that it couldn’t ‘manufacture’ endogenously anyway. Logic tells me that it therefore shouldn’t have a major effect on the level of autophagy…

          I’m not really so concerned about the sleep promoting effects of glycine though, since after suffering from insomnia when I was younger, I now sleep a lot better (particularly if I have had coffee a bit later than usual) through the intermittent use of 5-HTP capsules (2 x 50mg capsules every other night). These really do work, providing a very refreshing night’s sleep, and have the added bonus of quite often giving very lucid dreams! I don’t take them on the evening before my 3 x fast days though, since I’m figuring that tryptophan is an essential amino acid and will marginally interfere with autophagy, although not sure how much 100mg of 5-HTP would affect it. And I also read recently that tryptophan may be inflammatory. Have you read that too? I should probably scale back its use, but it just works so well…

          Reply
Big Jim says June 9, 2015

Isn’t bone broth usually petty high in glycine? Seems like this might be easy to achieve for those who consume broth regularly if so.

Reply
awesome says June 11, 2015

Since you recommended it we’ve been looking into NAC, it sounds like it’s ideally suited for my partner, so a big thanks for the tip.
We are planning to breed soon though; have you come across anything that says whether it’s indicated/contra during pregnancy? We saw one study where it decreased miscarriage in PCOS people (my partner doesn’t have PCOS) but other sources say to not take it during pregnancy?

Reply
    P. D. Mangan says June 12, 2015

    awesome, that I don’t know. Unless there have been studies specifically regarding taking during pregnancy, it’s always a good idea to exercise caution.

    May you have many healthy children!

    Reply
      awesome says June 12, 2015

      Thanks Mangan, we’ve been practicing so fingers crossed!

      Reply
Sam says June 15, 2015

Ok maybe this means nothing but as I was looking at a longevity page (probably crackpot) they said,”…Albumin is clearly the “Life Factor.” The major reservoir for albumin is the skin, representing approximately 1/3 of the body’s total pool. High serum albumin (>48g/L) ensures skin a healthy “glow”, promotes healing, digestion, nutrition and removal of waste products. This new understanding of the unique power of Super Hygiene to achieve/maintain the high – charge of the “skin battery” may change the understanding of medicine, including critical care, childhood development and aging…”

So then I search “Albumin glycine” and get some interesting results. Apparently lots of glycine in Albumin.

patent”…Growth hormone releasing factor (GRF) preparation which is excellent in stablity by having human serum albumin or glycine incorporated…”

https://www.google.com/patents/US4963529

Effect of Glycine on Human Serum Albumin Glycation-abstract

I couldn’t copy the abstract but it said that it mediated the damage from diabetes or high blood sugar damage.

http://downloads.arums.ac.ir/ICBC/Glycine.pdf

Anyways maybe nothing but the abstract looked interesting.

Reply
    P. D. Mangan says June 15, 2015

    Thanks, Sam. Albumin is a marker of aging. Very old people often have low serum albumin and it is, if I recall correctly, a marker for frailty and increased mortality risk. It’s very low in cancer cachexia. But how sensitive it is I don’t know, and it seems doubtful that the skin is a large reservoir for it; as far as I know all albumin is in the bloodstream.

    Added: “Serum albumin level is an independent risk factor for all-cause mortality in older persons.” http://jama.jamanetwork.com/article.aspx?articleid=380068

    “Our data demonstrate that hypoalbuminemia is not a consequence of normal aging.” http://geronj.oxfordjournals.org/content/43/1/M18.short

    Reply
Chris says June 15, 2015

I’m sorry to hear glycine didn’t help with your sleep. It is still going strong with me. I actually had to cut back when I started to get too excited.

I did some poking around on pubmed and found high doses, 0.8g/kg body weight, are used to treat refractory OCD and Schizophrenia. So apparently mega doses are safe and well tolerated, though they did titrate up.

I found an interesting case study of a boy with PANDAS, which is something I have, that may shed some light on my situation but I was using one twentieth the dose used in the case report.

“High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period”:

http://dx.doi.org/10.1155/2009/768398

I always learn so much following your tweets. They are excellent thought expiriments and jumping off points. It surprises me how rigid most of medicine is when biology is so flexible. Thanks for providing an alternative.

Reply
James Windham says August 4, 2015

I am interested in recent news in regard to glycine and how it can positively effect
respiration in the mitochondria of cells.
I have been taking a Nicotinamide Riboside supplement (Niagen) since last October, and
I can honestly say I feel stronger and more active than I did 10 years ago. By the way I’m 61.
Since NR acts positively on cells by increasing the amount of NAD in cells, which enables mitochondria to interact with the cell nucleus; I am wondering if taking a Glycine supplement could be further enhanced with NR supplementation or vice versa.
I have ordered some Glycine today and plan to start taking it along with NR.
We live in interesting times.

Reply
    Aurora says June 3, 2016

    Would love an update on your findings! …interesting times indeed!

    Reply
Robert says January 18, 2016

How did the combination go James Windham?

Reply
Glycine | weekly global research says July 29, 2016

[…] This is an exciting study and, although much more work will be needed, appears to open up a new avenue in potential anti-aging and life extension treatments. Best of all, glycine is cheap and likely very safe, since it’s an amino acid the body produces itself – P.D. Mangan […]

Reply
Arren Brandt says September 14, 2016

Glycine is not all its cracked up to be.

Michael Rae over at SRF took Glycine as a part of the question of the month. I Think you guys should read what he has to say about the original study.

http://www.sens.org/research/research-blog/question-month-11-are-mitochondrial-mutations-really-all-important

Reply
    P. D. Mangan says September 15, 2016

    I’ll give that (long) article a read, but for now just note that whether or not that’s correct, glycine still appears to mimic methionine restriction.

    Reply
Add Your Reply