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How to reconcile Sulfur Amino acid (SCAA/methionine) reduction benefits w/ other increase SCAA (Cysteine/NAC) benefits?

mentionine nac cystine scaa gsh glutathione liposiomal

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#1 ikon2

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Posted 09 November 2014 - 02:34 PM


There is increasingly strong evidence that methionine and Methionine/Cysteine ratio vs. Glycine/Serine ratio (and generally keeping sulfur containing amino acids SCAA's low) is similar, or may be to a large degree the reason behind CR life extension benefits, see:

 

 

Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1046-55. Epub 2007 Jun 13.

Restriction of sulfur-containing amino acids alters claudin composition and improves tight junction barrier function.

Skrovanek S, Valenzano MC, Mullin JM.

Source
The Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.

Abstract
Restriction of sulfur-containing amino acids (SCAA) has been shown to elicit a similar increase in life span and decrease in age-related morbidity as caloric restriction. The singular importance of epithelial barrier function in both physiological homeostasis and prevention of inflammation raised the issue of examining the effect of SCAA restriction on epithelial tight junction structure and permeability. Using a well-described in vitro, epithelial model, the LLC-PK(1) renal epithelial cell line, we studied the effects of SCAA restriction in culture medium. Reduction of methionine by 90%,
cysteine by 50%, and total elimination of cystine resulted in dramatically lower intracellular pools of these amino acids and their metabolite, taurine, but the intracellular pools of the non-SCAA were all elevated. Cell growth and differentiation were maintained, and both confluent cell density and transepithelial short circuit current were unaffected. Certain tight junctional proteins, such as occludin and claudins-1 and -2 were not altered. However, claudins-3 and -7 were significantly decreased in abundance, whereas claudins-4 and -5 were markedly increased in abundance. The functional result of these structural changes was improved barrier function, as evidenced by increased transepithelial electrical resistance and decreased transepithelial (paracellular) diffusion of D-mannitol.

 

This is just a small example.  There is a ton of info about this on many threads in this great forum.

 

But then again, Cysteine (and NAC especially) has many life extending implications as well, such as increasing Glutathione see this thread with links to lots of abstracts/studies: http://www.longecity...athione-by-300/

 

So the question to me becomes, is the net net better to restrict Cysteine levels or not?  Or is there a way to get the benefits of NAC for examples, while mitigating or removing Cysteine elsewhere, perhaps added Glycine/Serine?  But then again, Glycie acts as a IGF (or at least GH) secretagogue.

 

Do we have a consensus on what the best approach is on reconciling all of this?  I'm personally leaning toward dietary methionine restriction as much as possible (legumes, macadamia nuts, gelatin protein as it has no Menthionine) and then possibly adding only 600mg NAC/day?  The positives of NAC seem to always be targeted at Glutathione uptick.  Perhaps the better approach here would be liposomal Glutathione or RiboCeine?

 

Let's get some traction on his topic here as it seems to have two very hot topics among life-extensionists suggesting diametrically opposite things.

 


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#2 Adam Karlovsky

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Posted 15 January 2016 - 01:16 AM

I was going to start my own thread with the same question, but then did a search and found this. I think this really needs attention to get sorted, so I'd like to bump this thread, please.



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#3 Darryl

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Posted 15 January 2016 - 03:47 AM

Key papers:

 

Fukada SI et al. 2008. Effects of various amino acids on methionine-induced hyperhomocysteinemia in ratsBioscience, biotechnology, and biochemistry72(7), pp.1940-1943.

Cystine and N-acetylcysteine have hypohomocysteinemic effects in humans when administered as a single meal or a single dose. In contrast, dietary addition of cysteine did not decrease, but rather increased, the plasma homocysteine concentration in the present study. 

 

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Elshorbagy AK et al. 2011. Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturaseJournal of lipid research,52(1), pp.104-112.

We monitored obesity-related variables in 4 dietary groups for 12 weeks: control-fed (CF), methionine-restricted (MR), MR supplemented with 0.5% L-cysteine (MR+Cys) and CF+Cys rats. MR lowered weight gain and FM/BW% despite higher food intake/weight than CF, and lowered serum cysteine. Hepatic Scd1 expression was decreased, with decreased serum SCD1 activity indices (calculated from serum fatty acid profile), decreased serum insulin, leptin and triglycerides, and higher adiponectin. Cysteine supplementation (MR+Cys) essentially reversed all these phenotypes and raised serum cysteine but not methionine to CF levels.

 

Perrone CE et al. 2012. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscleJournal of nutrigenetics and nutrigenomics,5(3), pp.132-157.

Cysteine (supplementation) reversed some of methionine restriction’s effects in liver and upregulated the transcription of genes associated with inflammation and carcinogenesis such as Cxcl16 , Cdh17 , Mmp12 , Mybl1 , and Cav1 among others. 

 

Gomez A et al. 2015. Cysteine dietary supplementation reverses the decrease in mitochondrial ROS production at complex I induced by methionine restrictionJournal of bioenergetics and biomembranes47(3), pp.199-208.

Cysteine supplementation reverses the decrease in mitochondrial ROS generation induced by methionine restriction at complex I. Methionine restriction also decreased various markers of oxidative and non-oxidative stress on mitochondrial proteins which were not reversed by cysteine. Instead, cysteine supplementation also lowered protein damage in association with decreases in mTOR activation.

 

 

 

 

 

 

 

 


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Also tagged with one or more of these keywords: mentionine, nac, cystine, scaa, gsh, glutathione, liposiomal

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