#361

In the ITP, extremely high doses of glycine led to only a very small effect on lifespan.

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#362

Yes, glycine by itself will not provide the best benefit. Here’s the equation for Glutathione (GSH)

1 unit glycine + 1 unit cysteine + 1 unit glutamine = 1 unit GSH

Your body produces enough glutamine, so it’s not a limiting factor. Glycine and Cysteine are the limiters.

So if I give you 100 extra units of glycine but no extra units of cysteine, you’re not going to improve the amount of GSH as BOTH glycine and cysteine are the limiting AA. Hence why a lot of people supplement with GLYNAC (Glycine + Cysteine).

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#363

But if you go back to your original speculation:

As ReppinMycin posted earlier in the thread, taking cysteine (but not taurine) negates the beneficial metabolic effects of methionine restriction (which is never just Met restriction, but Met + Cys restriction).

Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase

So if your idea is that glycine will benefit longevity by lowering Met (and again, glycine itself has very little effect at massive doses), then taking Cys will nullify any Met-lowering effect.

Yes, I’m aware there’s a lifespan study claiming that GlyNAC extends lifespan in rodents. The controls were laughably short-lived, so it’s a meaningless result for a typical human, let alone a middle-class person with typical genetics living in an OECD country.

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#364

Yes, if you take cysteine by itself, it’s not a good idea. If you want to boost glutathione you need to supplement glycine and cysteine to optimize glutathione production.

There’s also this study on GLYNAC with humans.

The aging hallmarks that improved are mitochondrial dysfunction, altered intercellular communication, nutrient sensing, loss of proteostasis, genomic instability, cellular senescence and stem cell fatigue.

I make sure I take more glycine than cysteine. I take about 11 g of Glycine and about 3.2 g of Cysteine plus 8 g of Taurine daily.

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#365

“Yes, I’m aware there’s a lifespan study claiming that GlyNAC extends lifespan in rodents. The controls were laughably short-lived”

Thank you for sharing the above. I have missed that the controls were short lived.

Do you have any idea, what the result would have been if the controls had a normal lifespan?

#366

There are lots of studies showing that various antioxidants extend median and sometimes “maximum” lifespan relative to short-lived controls, and they almost never pan out in healthy well-cared-for mice; my hunch would be that the same would hold here. But the only way to know would be to re-do it in a more competent lab (and preferably with more mice).

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#367

GLYNAC mice.

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#368

Another way to think about it to see the change vs 900 instead of the controls 847

So even when handicapping the study this way (1,187 / 900 - 1) = 31.9% the longevity extension seems quite solid?

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#369

I think you’re thinking of this recent preprint, which set a benchmark of 900 days for the median lifespan of healthy control mice. But here you’re dividing the lifespan of the single longest-lived mouse by the median lifespan benchmark.

Also, you’re unwittingly exaggerating the maximum lifespan in this study: “maximum lifespan” does not mean the lifespan of the single longest-lived mouse, but the median lifespan of the longest-lived 10% of the animals. By definition, this is lower than the lifespan of the single longest-lived animal in the group. This is all made unreliable by the fact that the researchers only had 32 C57BL/6J mice in the entire study.

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#370

Yes, this treatment brought the BL6 mouse median to 889 days. So, it may be helpful for unhealthy people to obtain a longer lifespan.

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#371

Thanks @RapamycinCurious

There was no link to a paper in the post with the numbers, so you might very well be right about the average/ median / max point

I was just trying to provide a framework - if the controls live shorter one can stress test the data by applying a higher burden on the controls and see if there still is an effect left

I agree that it should be apples to apples

So if you want to handicap the improvement in maximum lifespan that could be done by using the max lifespan in normal controls (the same population where median is 900).

#372

Hi @DeStrider do you have the paper where these (and other numbers) can be found?

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#373

Here it is:

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#374

Thank you. That would put me at 5g/day, up from 3g, where I had been at for a couple of months. I’ll give that a try, since the 3g was showing good results (better energy, mood, & sleep.)

Any theories or thoughts about how taurine might best be taken around a rapa dose?

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#375

As ReppinMycin posted earlier in the thread, taking cysteine (but not taurine) negates the beneficial metabolic effects of methionine restriction (which is never just Met restriction, but Met + Cys restriction).

This issue could potentially be bypassed by supplementing gamma-glutamylcysteine rather than cysteine.

Btw there’s a study of NAC in UM-HET3 mice (same as ITP), although small sample size. No lifespan extension in the females but the males did show an increase. Looks like 50% of the controls lived at least ~840 days, so you could argue this isn’t an issue of short-lived controls. Either way, the two longest-lived mice in each NAC group lived at least 1,300 days, whereas the two longest-lived control mice lived about 900 days, which is a big difference. The authors suggested these could be CR effects though, as the NAC mice ate and drank less.

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#376

Thank you @DeStrider

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#377

I just put it in my coffee in the morning, which I have before any food. Doesn’t seem to affect the taste.

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#378

Thanks for the great idea!

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#379

From: https://www.pnas.org/content/115/43/10836 (Bruce Ames)

Taurine (2-Aminoethanesulfonic Acid).

Taurine is another example of a conditional vitamin because it is synthesized by animals (including humans), but not in sufficient amounts. It has been shown to be important in preventing numerous health problems, such as CVD, brain function, diabetes, and mitochondrial diseases, as summarized below. Because of taurine’s extensive involvement in health problems that lead to long-term damage, it is proposed here that it is also a longevity vitamin.

The synthesis of taurine involves cysteine decarboxylation and sulfhydryl oxidation. The rate of its biosynthesis is species-dependent, with a low level in humans, compared with rodents (which led to the suggestion that supplementation might be beneficial) (49). It is located in the cytosol and in mitochondria and it is present in virtually all human tissues at millimolar concentrations; it is especially high in electrically excitable and secretory tissues and in platelets. A 70-kg human contains about 70 g of taurine (50). An excellent review of all of the earlier work on taurine is available in Huxtable (50). Most of taurine is acquired from the diet, mainly from fish and other seafood, seaweed, eggs, and dark-meat poultry (51).

Taurine is particularly important in the mitochondria, where it is present as 5-taurinomethyl-uridine in tRNA-leu and tRNA-trp, and as 5-taurinomethyl-2-thiouridine in tRNA-glu, tRNA-gln, and tRNA-lys. In all five tRNAs, it is located in the wobble position, where it functions to read accurately alternate codons in the mitochondrial genome (52). A taurine modification defect in mitochondrial tRNA is associated with the mitochondrial diseases MELAS (mitochondrial encephalopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonus epilepsy with ragged-red fibers) (52), suggesting causality, and also that a taurine deficiency could result in the same diseases. Because of the involvement of mitochondria in energy production, there has been much interest in taurine in sports medicine in humans with reference to exercise-induced fatigue and recovery, as has been reviewed previously (53). In addition, a strong case has been made that taurine is the main buffer in mitochondria (54) and that it moderates mitochondrial oxidant production (55).

Another possibly important function of taurine is its detoxification of chloramine (a very toxic membrane-soluble oxidant) via its conversion to taurine-chloramine (56, 57).

Examples of several important insidious long-term pathologies that taurine would protect against are: CVD, brain dysfunction, and diabetes. Taurine effects on CVD have been examined by numerous RCTs and have been reviewed previously (51). Taurine supplementation lowers blood pressure, improves vascular function, and raises plasma hydrogen sulfide levels as shown in a recent RCT with prehypertension patients (58). Taurine consumption was the most significant factor associated with reduced risk of ischemic heart disease (IHD) in two international epidemiological studies of CVD in 61 populations (25 countries; n = 14,000): Japanese people in Okinawa had the highest taurine dietary intake and the lowest incidence of IHD and longest lifespan. In contrast, Japanese immigrants in Brazil who eat little seafood, but more meat and salt, had a 17-y shorter lifespan as a consequence of a very high IHD mortality (59). Other human clinical studies showed that taurine decreases platelet aggregation, serum cholesterol levels, LDL/triglyceride levels, and enhances cardiac function (60).

Taurine plays an important role in brain development, including neuronal proliferation, stem cell proliferation, and differentiation; it has no toxic effects in humans (61). It is a neuromodulator in the central nervous system: it activates the GABA- and glycine-insensitive chloride channel and it inhibits the N-methyl-d-aspartate receptor. It is also neuroprotective and has a role in neural development and neurogenesis; it was shown in an RCT that symptoms of psychopathology were improved by its administration in patients with first-episode psychosis (62).

Diabetic remediation by taurine has been reviewed previously (63, 64). Its supplementation remediates diabetic pathologies, including retinopathy, neuropathy, nephropathy, cardiopathy, atherosclerosis, altered platelet aggregation, and endothelial dysfunction (65). In patients with type 1 and type 2 diabetes the taurine transporter is up-regulated in mononuclear blood cells, indicating that increased levels of taurine are sought by the cell (66, 67). In rats, taurine reduces oxidative stress caused by diabetes (68, 69).

Taurine is important for fetal development, because the human fetus cannot synthesize taurine, which is provided by the mother via the taurine transporter, and it is necessary for organ development and protects against development of type 2 diabetes (70). Therefore, taurine is also a survival vitamin. Transport of taurine (53) is required for normal development of numerous fetal tissues in several experimental animals. Taurine functions as an osmolyte; it was shown to be important in that respect in a variety of species, including rodent investigations that are consistent with the above results on humans (70, 71) (SI Appendix, SI-4 Conditional Vitamins).

Taurine is well established as an important conditional vitamin for survival functions and for healthy longevity in both humans and experimental animals. I expect that a large class of new conditional vitamins will be discovered. Possible candidates are lipoic acid, ubiquinone, and carnitine.

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#380

I didn’t see Nutricost tested on the Taurine page on consumerlab. Where did you see that?