7 replies to this topic

[s123]

Restriction of sulfur-containing amino acids alters claudin composition and improves tight junction barrier function
S. Skrovanek,1 M. C. Valenzano,2 and J. M. Mullin1,2,3
1Department of Biology, Saint Joseph's University, Philadelphia, Pennsylvania; 2The Lankenau Institute for Medical Research, Wynnewood, Pennsylvania; and 3Division of Gastroenterology, Lankenau Hospital, Wynnewood, Pennsylvania

Submitted 31 January 2007 ; accepted in final form 11 June 2007


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-PK1 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.

I think that we've all heard about the life extending effect of a low methionine diet but it seems that restricting cysteine and eliminating cystine in a diet also expends your live. The metabolite of these amino acids is taurine. A lot of people here are taking taurine and cysteine (whey protein powder and previously NAC).

[zoolander]

and then there is the other side of the coin in that a deficiency in cysteine or cellular redox state accelerates aging

Curr Drug Targets. 2006 Nov;7(11):1505-12.Click here to read Links
    The deficit in low molecular weight thiols as a target for antiageing therapy.
    Dröge W, Kinscherf R, Hildebrandt W, Schmitt T.

    Division of Redox Physiology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. W.Droege@dkfz.de

    The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that ROS can function as biological signaling molecules without excessive tissue damage, ROS are typically scavenged by antioxidants such as glutathione and the vitamins A, C, and E. "Oxidative stress" occurs if the production of ROS is abnormally increased or antioxidant concentrations are decreased. Genetic studies in mice, Drosophila, and C.elegans suggested that ageing may be mechanistically linked to oxidative stress. Several manifestations of oxidative stress were shown to increase with age, whereas tissue levels of vitamin E, plasma concentrations of vitamin C, and intracellular glutathione concentrations decrease with age. In at least two independent studies, cysteine supplementation on top of the normal protein diet has shown significant beneficial effects on each of several different parameters relevant to ageing, including skeletal muscle functions. As the quality of life in old age is severely compromised by the loss of skeletal muscle function, and as muscle function can be measured with satisfactory precision, loss of muscle function is one of the most attractive surrogate parameters of ageing. The mechanisms by which a deficit in glutathione and its precursor cysteine contributes to various ageing-related degenerative processes appears to be related largely but not exclusively to the dysregulation of redox-regulated biological signaling cascades.

    PMID: 17100590 [PubMed - indexed for MEDLINE]

[s123]

and then there is the other side of the coin in that a deficiency in cysteine or cellular redox state accelerates aging

Curr Drug Targets. 2006 Nov;7(11):1505-12.Click here to read Links
    The deficit in low molecular weight thiols as a target for antiageing therapy.
    Dröge W, Kinscherf R, Hildebrandt W, Schmitt T.

    Division of Redox Physiology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. W.Droege@dkfz.de

    The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that ROS can function as biological signaling molecules without excessive tissue damage, ROS are typically scavenged by antioxidants such as glutathione and the vitamins A, C, and E. "Oxidative stress" occurs if the production of ROS is abnormally increased or antioxidant concentrations are decreased. Genetic studies in mice, Drosophila, and C.elegans suggested that ageing may be mechanistically linked to oxidative stress. Several manifestations of oxidative stress were shown to increase with age, whereas tissue levels of vitamin E, plasma concentrations of vitamin C, and intracellular glutathione concentrations decrease with age. In at least two independent studies, cysteine supplementation on top of the normal protein diet has shown significant beneficial effects on each of several different parameters relevant to ageing, including skeletal muscle functions. As the quality of life in old age is severely compromised by the loss of skeletal muscle function, and as muscle function can be measured with satisfactory precision, loss of muscle function is one of the most attractive surrogate parameters of ageing. The mechanisms by which a deficit in glutathione and its precursor cysteine contributes to various ageing-related degenerative processes appears to be related largely but not exclusively to the dysregulation of redox-regulated biological signaling cascades.

    PMID: 17100590 [PubMed - indexed for MEDLINE]

I know, that's the part that confuses me. Do we have to eat 'a lot' of cysteine or do we have to restrict it??? Once again we see the complexity of our bodies.

[speda1]

I don't know the answer, but I wonder if the benefits of methionine restriction are related to homocysteine reduction or if there is another mechanism...perhaps a reduction in overall anabolism.

[niner]

I know, that's the part that confuses me. Do we have to eat 'a lot' of cysteine or do we have to restrict it??? Once again we see the complexity of our bodies.

Well, if a cysteine deficit contributes to markers of aging, then you would want to get more of it.

[zoolander]

come on guys lets get real here......there are multiple studies in humans showing benefit of modifying the GSH/GSSG using a cysteine donor. The first quoted study was an in vitro cell culture study using a single cell line. So we're comparing a study that says pro-aging from an in vitro cell culture studies to studies that say possible anti-aging using in vivo human studies.

If I had to choose the more appropriate conclusion I know which one I would choose

[graatch]

Do we have to eat 'a lot' of cysteine or do we have to restrict it???

Supplement proper amounts.

It's not surprising sulfur compounds can be toxic if you go past a certain dose window. We already "know" NAC can be pro-oxidant (among other problems) if dosed at the wrong times, or in excess.

But we also "know" getting the proper amounts of these compounds can have great benefits.

[s123]

I don't know the answer, but I wonder if the benefits of methionine restriction are related to homocysteine reduction or if there is another mechanism...perhaps a reduction in overall anabolism.

Methionine restriction would cause a stress on the body similar to calorie restriction and that stress would lengthen your life.
You can have the same benefit from restricting tryptophan.