Methionine/Cysteine restriction increases longetivity AND energy expenditure
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@Mauritio heh
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Great thread @Mauritio, I read through the whole thread - bravo to you and the others that contributed
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Another interesting fun fact is that the high carb diet increased the concentration of palmitoleic acid by almost 150%. Its interesting that when the body makes new fat that it is a pro-metabolic MUFA. Palmitoelic acid is contained in macadamia nuts a lot.
"Diabetes induced a decrease of monounsaturated fatty acids and particularly palmitoleic acid in all studied tissues: liver,
aorta, plasma."
https://www.sciencedirect.com/science/article/abs/pii/095528639500026V -
On this website they offer a chart with methionine levels of all kinds of foods.
Apparently people in need of it, can also order methioniase.
Also lots of studies on methionine and cancer .
If someone wants to support real cancer research, thats the way to go.
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio - Thanks for the info and the chart. Here is the chart that I use; it is less precise but it gets the job done.
I revisited Dr. Peat's thoughts on lowering methionine. The approach that I like is to focus on dietary restrictions. Lower sulfur containing amino acids (methionine, cysteine) and higher amounts of gelatin/glycine.
Peatbot.com: To lower methionine intake, you can focus on dietary strategies that reduce the consumption of foods high in methionine. Methionine is an amino acid found in high-protein foods, particularly in muscle meats. Here are some approaches to consider:
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Reduce High-Protein Foods: Limit the intake of foods that are high in methionine, such as muscle meats. Instead, focus on consuming proteins that are lower in methionine.
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Incorporate Gelatin: Gelatin is a protein source that is free of the pro-aging amino acids like methionine. Including gelatin in your diet can help balance the intake of amino acids.
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Balance with Other Protein Sources: Consider consuming proteins from the whole animal, including connective tissues, which provide a more balanced amino acid profile compared to muscle meats alone.
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Increase Plant-Based Proteins: Plant-based proteins generally have lower methionine content compared to animal-based proteins. Incorporating more plant-based foods can help reduce methionine intake.
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Methionine Restriction: Actively restrict methionine intake by being mindful of the protein sources you choose, aiming for those with lower methionine content.
By following these strategies, you can effectively lower methionine intake, which has been associated with increased lifespan in some studies.
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Obesity is a fibroblast growth factor 21 (FGF21)-resistant state
https://pubmed.ncbi.nlm.nih.gov/20682689/ -
FGF21 overexpression alleviates VSMC senescence in diabetic mice by modulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway
https://pmc.ncbi.nlm.nih.gov/articles/PMC11214975/ -
"...we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis."
https://pubmed.ncbi.nlm.nih.gov/40527315/ -
C3G the polyphenol from elderberries increases FGF21 4-fold in the liver.
https://pubmed.ncbi.nlm.nih.gov/32470979/ -
I’m not sure cysteine is bad. There seems to be evidence (the short Baylor study for instance) that cysteine supplementation can be helpful. And cysteine <—-> methionine seems to be a metabolically expensive path and not much methionine is created by cysteine consumption. So I’m thinking NAC could be helpful.
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@Ecstatic_Hamster If your read this thread, you'll see that even a small amount of cysteine can remove almost all benefits from methionine restriction.
@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Just like a small amount of cysteine removed almost all the benefits of MR in this study.
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@Mauritio thank you!
What do you make of the Baylor study?
Yes it’s short. But it points the way because they assessed a blend of signals that all showed much more youth and vigor in the subjects.
https://pubmed.ncbi.nlm.nih.gov/33783984/
Background: Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel-oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improves naturally-occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition.Methods: A 36-week open-label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre-supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red-blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait-speed, grip-strength, 6-min walk test; cognitive tests; genomic-damage; glucose-production and muscle-protein breakdown rates; and body-composition.
Results: GlyNAC supplementation for 24 weeks in OA corrected RBC-GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin-resistance, genomic-damage, cognition, strength, gait-speed, and exercise capacity; and lowered body-fat and waist-circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks.
Conclusions: GlyNAC supplementation for 24-weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin-resistance and endothelial dysfunction, and genomic-damage, and improved strength, gait-speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.
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I've read through this thread again and pulled out some interesting bits for me:
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Selenium supplementation, via the metabolite through hydrogen selenite, breaks down collagen. On the plus side this may tackle (liver) fibrosis. The drawback is broken down collagen (hair, skin) and a therefore probably significantly increased demand for resynthesis from glycine, ascorbic acid, prolin (via ornithine/arginine/citrullin).
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The control feed + cysteine studies in rodents and the GlyNAC studies in humans sort of tell the tale:
If not doing MetR + CysR then a regular diet supplemented with cysteine actually consistently looks better in several aspects including body composition, fat pads, strength, inflammation. Peculiar.
The control feed + cysteine in rodents resulted even in better looking markers than MetR + cysteine. Strange. -
I surmise there must be crucially overlooked specific discrepancies in the transfer of mice study results to humans. Perhaps not least because glutathione is much more crucial for redox homeostasis and substance conjugation in non-ascorbic-acid-synthesizing humans in comparison to mice. Bridging to 4):
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Regularly increased glycine and citrulline intakes to both balance the relative ratio to and the absolute uptake of Met and to scavenge methyl groups in the metabolism after absorption do appeal.
Very obviously, large protein intakes are bad for longevity not merely because of mTOR activation. Eating a typical protein composition but in low to moderate amounts only as in the previously quoted low-protein diets enhanced by extra glycine and citrulline (+proline) appeals. The latter will also benefit the maintenance and rebuilding of collagen structures and allow for use of selenium supplementation to reap to a large extent the quoted increase of fgf21.
Glycine also lowers its absorption. Although it's more true to say that methionine lowers glycines absorption , IIRC up to 86% !
"...l-Met uptake is very potently inhibited by l-arginine, l-citrulline, l-lysine and l-isoleucine in the rat intestine 53. "So if Met inhibits Gly absorption, and Cit inihibits Met absorption,
then Gly+Cit is ought to bring about win-win conditions. -
