Low levels of methionine, cystathionine, choline, succinate, malate and high levels of non-polar amino acids, carnitine are associated with longevity

[aliml]

Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content. The present study follows a comparative approach to analyse plasma methionine metabolic profile using a LC-MS/MS platform from 11 mammalian species with a longevity ranging from 3.5 to 120 years. Our findings demonstrate the existence of a species-specific plasma profile for methionine metabolism associated with longevity characterised by:
i) reduced methionine, cystathionine and choline;
ii) increased non-polar amino acids (alanine, glycine, leucine, isoleucine, phenylalanine, proline, tryptophan and valine);
iii) reduced succinate and malate; and
iv) increased carnitine. Our results support the existence of plasma longevity features that might respond to an optimised energetic metabolism and intracellular structures found in long-lived species.

Plasma methionine metabolic profile is associated with longevity in mammals

Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content. The present study follows a comparative approach to analyse plasma ...

www.ncbi.nlm.nih.gov

Mechanisms to sense levels of the essential amino acid methionine are one of the more important triggers for the beneficial calorie restriction response in mammals. Since the body doesn't manufacture methionine, it must come from the diet. Either a low calorie diet or a low methionine diet produce broadly similar effects of improved metabolism, health, and longevity, though different in the fine details. Short-lived species, however, have a much larger gain in life span than is the case in longer-lived species. Calorie restriction can make mice live 40% longer, but it certainly doesn't add more than a few years in humans.

Why this is the case, when short-term metabolic responses and benefits appear broadly similar in both short-lived and long-lived mammals, is an open question. In this context, the research here is quite interesting. If background levels of methionine are lower in long-lived species, perhaps the shared trigger mechanisms relating to methionine are less capable of producing sizable effects in long-term health - though again, a detailed understanding of exactly how this happens has yet to be established.

Long Lived Mammals Exhibit Lower Plasma Methionine Levels

Mechanisms to sense levels of the essential amino acid methionine are one of the more important triggers for the beneficial calorie restriction response in mammals. Since the body doesn't manufacture methionine, it must come from the diet. Either a low calorie diet or a low methionine diet...

fightaging.org

 

[Grapelander]

The curves were down (lowering life expectancy) for the sulfur containing amino acids.
The longevity effects of transsulfuration have been attributed to the generation of molecules with antioxidant properties, such as hydrogen sulfide (H2S), glutathione and taurine. However, our study reveals that plasma transsulfuration intermediates or products remain unchanged (homocysteine and cysteine) across species, and even decreased (cystathionine, glutathione and taurine) in long-lived mammalian species. Under the presumption that “less is more” in long-lived species, we suggest that the steady-state levels of these intermediates are not increased since long-lived species produce less intracellular damage and are structurally built upon more resistant molecules. Therefore, these long-lived species do not need to synthetize a vast amount of antioxidant and can re-direct the energy saved to maintain other vital cellular functions.

However the curves were up for B6 and P5P.

 

[J.R.K]

S

The curves were down (lowering life expectancy) for the sulfur containing amino acids.
The longevity effects of transsulfuration have been attributed to the generation of molecules with antioxidant properties, such as hydrogen sulfide (H2S), glutathione and taurine. However, our study reveals that plasma transsulfuration intermediates or products remain unchanged (homocysteine and cysteine) across species, and even decreased (cystathionine, glutathione and taurine) in long-lived mammalian species. Under the presumption that “less is more” in long-lived species, we suggest that the steady-state levels of these intermediates are not increased since long-lived species produce less intracellular damage and are structurally built upon more resistant molecules. Therefore, these long-lived species do not need to synthetize a vast amount of antioxidant and can re-direct the energy saved to maintain other vital cellular functions.

However the curves were up for B6 and P5P.
View attachment 32735

Sorry for my simplistic mind in not grasping this fully. But are we advocating in this study to reduce methionine and sulphur as well? @alimi @Grapelander
Also not quite grasping on whether taurine and glutathione are good things or bad for longevity?

 

[InChristAlone]

Some of the most long lived people do have low protein diets.

 

[J.R.K]

Some of the most long lived people do have low protein diets.

This is true, but I am of the understanding that Dr Peat advocates for,”adequate protein”. Now that will leave things pretty wide open as each person’s lifestyle and activity levels are going to be different.
My current philosophy on this is to try to aim for a two to three to one carbohydrate to protein levels. With an attempt to minimize fat with that fat being as saturated as possible. But I realize that PUFA is very abundant everywhere, so as @haidut has said we make the best choices possible given our choices.
I am still an advocate for leafy green vegetables but always well cooked, I can tolerate raw salads I always have but somehow it just makes sense for me to boil the leafy greens in order to maximize the bioavailability of their nutrients, plus I love collard greens.

 

[Peat Tong]

interesting. any way to make more enzymes that convert methionine into carnitine? or just add more lysine?

 

[Grapelander]

S

Sorry for my simplistic mind in not grasping this fully. But are we advocating in this study to reduce methionine and sulphur as well? @alimi @Grapelander
Also not quite grasping on whether taurine and glutathione are good things or bad for longevity?

Some people will benefit from glutathione if they have a damaged anti-oxidant system; most will not as there is a fine balance of oxidant/anti-oxidants in the body.
Dr. Peat for the most part does not favor sulfur in high doses; or methionine / cysteine. Ray mentions restricting methionine increases glutathione.
Think about getting sulfur from thiamine and biotin first.

Protective CO2 and aging

Parental stress, prenatal stress, early life stress, and even stress in adulthood contribute to “imprinting of the genes,” partly through methylation of DNA and the histones.
Methionine and choline are the main dietary sources of methyl donors. Restriction of methionine has many protective effects, including increased average (42%) and maximum (44%) longevity in rats (Richie, et al., 1994). Restriction of methyl donors causes demethylation of DNA (Epner, 2001). The age accelerating effect of methionine might be related to disturbing the methylation balance, inappropriately suppressing cellular activity. Besides its effect on the methyl pool, methionine inhibits thyroid function and damages mitochondria.

Tryptophan, serotonin, and aging
...cysteine, and cysteine, methionine, and tryptophan suppress thyroid function (Carvalho, et al., 2000).
Methionine restriction increases blood glutathione and longevity in F344 rats. Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA “Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001).”

Meat physiology, stress, and degenerative physiology​

Increasing carbon dioxide will tend to direct ammonia into urea synthesis, and away from the formation of polyamines. Bicarbonate protects against many of the toxic effects of ammonia, and since carbon dioxide spontaneously reacts with amino groups, it probably helps to inactivate exogenous polyamines. This could account for some of the protective effects of carbon dioxide (or high altitude), for example its anti-seizure, anticancer, and antistress effects.

Other things that protect against excessive polyamines are procaine and other local anesthetics (Yuspa, et al., 1980), magnesium, niacin, vitamin A, aspirin, and, in some circumstances, caffeine. Since endotoxin stimulates the formation of polyamines, a diet that doesn't irritate the intestine is important. Tryptophan and methionine contribute to the formation of polyamines, so gelatin, which lacks those amino acids and is soothing to the intestine, should be a regular part of the diet.

Because the polyamines intensify the neurotoxic and carcinogenic effects of estrogen and of polyunsaturated fats, those three types of substance should be considered as a functional unit in making food choices. (Grass-fed organic beef fresh from a local farm would be a reasonable choice.)

Generative Energy
When I heard Carl Pfeiffer speak, I noticed that both his skin and his hair were free of pigment, though he was not an albino, and I wondered whether his various mineral nutritional supplements had contributed to his fading. (He took sulfur every day, and avoided copper. He also advocated the use of molybdenum as a nutritional supplement.)
Natural progesterone therapy in the form described above remains the most direct and general treatment for PMS; thyroid and vitamin A, and other normalizer's of mitochondrial respiration, such as red light and short chain saturated fats, act in the same direction. Fiber, bowel stimulants and antispasmodics, and broad spectrum bowel "disinfectants" such as flowers of sulfur, sodium thiosulfate, and short and medium-chain saturated fatty acids, can contribute to alleviation of premenstrual symptoms.

Townsend Newsletter
When flowers of sulfur is taken orally, some of it becomes available for use in the rhodanese system. lt might be less irritating and more effective to use a form of sulfur which is chemically more available, namely thiosulfate. (My thoughts on light removing carbon monoxide from cytochromes led me to think about photography; sodium thiosulfate is used to clear the photographic emulsion, removing the silver which was not exposed to light. In that sense, its activity as a reductant is equivalent to light's action).
In acute cyanide poisoning, a large dose of sodium thiosulfate (l2grams) is injected rapidly; it is poorly absorbed when taken orally. I decided to try small oral doses,
about 50 mg. a few times per day. It has improved my tolerance for chocolate and wheat, which I still reacted to in spite of using pregnenolone, which was permitting
me to eat many other foods that earlier would have caused migraines and asthma. Pregnenolone seems to stabilize the cytochromes physically, while rhodanese
(with sulfur) restores their chemical activity. Some druggists still sell sodium thiosulfate as a treatment for skin diseases. It has been used to treat arthritis, which would be logical if it is able to increase formation of pregnenolone and the various steroid hormones.

Hormone-Related Brain Syndromes
Nutritional supplements that might help to prevent or correct these brain syndromes include: Vitamin E and coconut oil; vitamin A; magnesium, sodium; thyroid which includes T3; large amounts of animal protein, especially eggs; sulfur, such as magnesium sulfate or flowers of sulfur, but not to take continuously, because of sulfur's interference with copper absorption; pregnenolone; progesterone if needed. Bright light, weak in the blue end of the spectrum and with protection against ultraviolet, activates respiratory metabolism and quenches free radicals. Raw carrot fiber and/or laxatives if needed; charcoal occasionally for gas or bowel irritation. Coconut oil serves several purposes. Its butyric acid is known to increase T3 uptake by glial cells. It has a general pro-thyroid action, for example by diluting and displacing anti-thyroid unsaturated oils, its short-and medium-chain fatty acids sustain blood sugar and have anti-allergic actions, and it protects mitochondria against stress injury.

 

[J.R.K]

Some people will benefit from glutathione if they have a damaged anti-oxidant system; most will not as there is a fine balance of oxidant/anti-oxidants in the body.
Dr. Peat for the most part does not favor sulfur in high doses; or methionine / cysteine. Ray mentions restricting methionine increases glutathione.
Think about getting sulfur from thiamine and biotin first.

Protective CO2 and aging

Parental stress, prenatal stress, early life stress, and even stress in adulthood contribute to “imprinting of the genes,” partly through methylation of DNA and the histones.
Methionine and choline are the main dietary sources of methyl donors. Restriction of methionine has many protective effects, including increased average (42%) and maximum (44%) longevity in rats (Richie, et al., 1994). Restriction of methyl donors causes demethylation of DNA (Epner, 2001). The age accelerating effect of methionine might be related to disturbing the methylation balance, inappropriately suppressing cellular activity. Besides its effect on the methyl pool, methionine inhibits thyroid function and damages mitochondria.

Tryptophan, serotonin, and aging
...cysteine, and cysteine, methionine, and tryptophan suppress thyroid function (Carvalho, et al., 2000).
Methionine restriction increases blood glutathione and longevity in F344 rats. Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA “Met restriction resulted in a 42% increase in mean and 44% increase in maximum life span, and in 43% lower body weight compared to controls (P < 0.001). Increases in blood GSH levels of 81% and 164% were observed in mature and old Met-restricted animals, respectively (P < 0.001).”

Meat physiology, stress, and degenerative physiology​

Increasing carbon dioxide will tend to direct ammonia into urea synthesis, and away from the formation of polyamines. Bicarbonate protects against many of the toxic effects of ammonia, and since carbon dioxide spontaneously reacts with amino groups, it probably helps to inactivate exogenous polyamines. This could account for some of the protective effects of carbon dioxide (or high altitude), for example its anti-seizure, anticancer, and antistress effects.

Other things that protect against excessive polyamines are procaine and other local anesthetics (Yuspa, et al., 1980), magnesium, niacin, vitamin A, aspirin, and, in some circumstances, caffeine. Since endotoxin stimulates the formation of polyamines, a diet that doesn't irritate the intestine is important. Tryptophan and methionine contribute to the formation of polyamines, so gelatin, which lacks those amino acids and is soothing to the intestine, should be a regular part of the diet.

Because the polyamines intensify the neurotoxic and carcinogenic effects of estrogen and of polyunsaturated fats, those three types of substance should be considered as a functional unit in making food choices. (Grass-fed organic beef fresh from a local farm would be a reasonable choice.)

Generative Energy
When I heard Carl Pfeiffer speak, I noticed that both his skin and his hair were free of pigment, though he was not an albino, and I wondered whether his various mineral nutritional supplements had contributed to his fading. (He took sulfur every day, and avoided copper. He also advocated the use of molybdenum as a nutritional supplement.)
Natural progesterone therapy in the form described above remains the most direct and general treatment for PMS; thyroid and vitamin A, and other normalizer's of mitochondrial respiration, such as red light and short chain saturated fats, act in the same direction. Fiber, bowel stimulants and antispasmodics, and broad spectrum bowel "disinfectants" such as flowers of sulfur, sodium thiosulfate, and short and medium-chain saturated fatty acids, can contribute to alleviation of premenstrual symptoms.

Townsend Newsletter
When flowers of sulfur is taken orally, some of it becomes available for use in the rhodanese system. lt might be less irritating and more effective to use a form of sulfur which is chemically more available, namely thiosulfate. (My thoughts on light removing carbon monoxide from cytochromes led me to think about photography; sodium thiosulfate is used to clear the photographic emulsion, removing the silver which was not exposed to light. In that sense, its activity as a reductant is equivalent to light's action).
In acute cyanide poisoning, a large dose of sodium thiosulfate (l2grams) is injected rapidly; it is poorly absorbed when taken orally. I decided to try small oral doses,
about 50 mg. a few times per day. It has improved my tolerance for chocolate and wheat, which I still reacted to in spite of using pregnenolone, which was permitting
me to eat many other foods that earlier would have caused migraines and asthma. Pregnenolone seems to stabilize the cytochromes physically, while rhodanese
(with sulfur) restores their chemical activity. Some druggists still sell sodium thiosulfate as a treatment for skin diseases. It has been used to treat arthritis, which would be logical if it is able to increase formation of pregnenolone and the various steroid hormones.

Hormone-Related Brain Syndromes
Nutritional supplements that might help to prevent or correct these brain syndromes include: Vitamin E and coconut oil; vitamin A; magnesium, sodium; thyroid which includes T3; large amounts of animal protein, especially eggs; sulfur, such as magnesium sulfate or flowers of sulfur, but not to take continuously, because of sulfur's interference with copper absorption; pregnenolone; progesterone if needed. Bright light, weak in the blue end of the spectrum and with protection against ultraviolet, activates respiratory metabolism and quenches free radicals. Raw carrot fiber and/or laxatives if needed; charcoal occasionally for gas or bowel irritation. Coconut oil serves several purposes. Its butyric acid is known to increase T3 uptake by glial cells. It has a general pro-thyroid action, for example by diluting and displacing anti-thyroid unsaturated oils, its short-and medium-chain fatty acids sustain blood sugar and have anti-allergic actions, and it protects mitochondria against stress injury.

Thank you for this information @Grapelander, it helps to connect more dots and widen my knowledge. I had no idea that thiamine and biotin were helping with sulphur and glutathione. I use eggs daily and knew they had sulphur as well as antiviral in raw form.
My questions always arose during the Patrick Timpone show where they advertise a sulphur product for daily consumption I think Patrick said at one point he uses up to three teaspoons a day. But this information for myself reinforced my initial thoughts on using flowers of sulphur as a gut disinfectant in times of ill health.
As for methonine I am going to keep with the glass of grape juice following red meat consumption, I think there is something in the studies that indicates it inhibits the uptake of methionine.

 

[Grapelander]

As for methonine I am going to keep with the glass of grape juice following red meat consumption, I think there is something in the studies that indicates it inhibits the uptake of methionine

This is good info - now I also have a reason to drink grape juice. Thank you.
Protective Effect of Purple Grape Juice
Sreemantula et al. showed the antioxidant activity of the purple grape extract with the Hydroxyl Radical Assay Method. They determined that the antioxidant activity of the vitis vinifera extract was 8 times higher than ascorbic acid. James et al. reported that short-term administration of purple grape juice to the patients with coronary artery diseases improved the endothelial functions and decreased the LDL oxidation sensitivity.

The comparable antioxidant activities of red and purple grapes are well known. All of these fruit extracts have high activity against the superoxide radicals, which are released through various chemical pathways. Another feature of these extracts is the inhibitory effect on the xanthine oxidase enzyme, which initiates the production of the free radicals within the cell. The primary modification reactions cause the synthesis of the protein carbonyl derivatives. As a result of the interaction of the reactive oxygen derivatives with the proteins, protein carbonyl products emerge due to the oxidative damage, which occurs on the peptide backbone of several amino acids like histidine, proline, arginine and lysine or proteins. The measurement of the protein carbonyl levels is a sensitive and widely used method for the determination of the protein oxidation

 

[Andy316]

As for methonine I am going to keep with the glass of grape juice following red meat consumption, I think there is something in the studies that indicates it inhibits the uptake of methionine.

Does the grape juice work?

 

[J.R.K]

Does the grape juice work?

I believe it does have an effect I never really did any blood tests in order to verify but there are studies suggesting that it does. I feel however that the polyphenols and other nutrients within are beneficial, as well Dr Peat has mentioned that there is a heavy metal chelation benefit as well.