5 replies to this topic

[lauritta]

According to some studies, free radical leakage (mainly in Complex I of the respiratory chain) is associated with both aging and disease. Uncoupling the respiratory chain could have the potential to extend lifespan. What do you think about that? What kind of techniques or chemicals could be used to try this? ideas? objections?

[caston]

http://www.ncbi.nlm....pt=AbstractPlus

[lauritta]

Thank you Caston!
I found another paper very interesting too:

FASEB J. 2006 Jun;20(8):1064-73.
Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins.
Sanz A, Caro P, Ayala V, Portero-Otin M, Pamplona R, Barja G.
Department of Animal Physiology-II, Complutense University, Madrid, Spain.

Previous studies have consistently shown that caloric restriction (CR) decreases mitochondrial reactive oxygen species (ROS) (mitROS) generation and oxidative damage to mtDNA and mitochondrial proteins, and increases maximum longevity, although the mechanisms responsible for this are unknown. We recently found that protein restriction (PR) also produces these changes independent of energy restriction. Various facts link methionine to aging, and methionine restriction (MetR) without energy restriction increases, like CR, maximum longevity. We have thus hypothesized that MetR is responsible for the decrease in mitROS generation and oxidative stress in PR and CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their longevity. We have found, for the first time, that MetR profoundly decreases mitROS production, decreases oxidative damage to mtDNA, lowers membrane unsaturation, and decreases all five markers of protein oxidation measured in rat heart and liver mitochondria. The concentration of complexes I and IV also decreases in MetR. The decrease in mitROS generation occurs in complexes I and III in liver and in complex I in heart mitochondria, and is due to an increase in efficiency of the respiratory chain in avoiding electron leak to oxygen. These changes are strikingly similar to those observed in CR and PR, suggesting that the decrease in methionine ingestion is responsible for the decrease in mitochondrial ROS production and oxidative stress, and possibly part of the decrease in aging rate, occurring during caloric restriction.

PMID: 16770005 [PubMed - indexed for MEDLINE]

http://www.fasebj.or...print/20/8/1064

[Futurist1000]

Hmm, that's interesting about the methionine restriction.

This could be another reason why selenium supplementation might be beneficial for life expectancy (Seems to be one of the few supplements that actually increases lifespan). Selenium affects methionine sulfoxide reductase. This leads to a reduction in methionine oxidation.

Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues

Mammals contain two methionine sulfoxide (MetO) reductases, MsrA and MsrB, that catalyze the thioredoxin-dependent reduction of the S-MetO and R-MetO derivatives, respectively, to methionine. The major mammalian MsrB is a selenoprotein (except in the heart). Here, we show that there is a loss of MsrB activity in the MsrA–/– mouse that correlates with parallel losses in the levels of MsrB mRNA and MsrB protein, suggesting that MsrA might have a role in MsrB transcription. Moreover, mice that were grown on a selenium-deficient (SD) diet showed a substantial decrease in the levels of MsrB-catalytic activity, MsrB protein, and MsrB mRNA in liver and kidney tissues of both WT and MsrA–/– mouse strains. Whereas no significant protein-MetO could be detected in tissue proteins of young mature mice grown on a selenium-adequate diet, growth on the SD diet led to substantial accumulations of MetO in proteins and also of protein carbonyl derivatives in the liver, kidney, cerebrum, and cerebellum, respectively. In addition, accumulation of protein-MetO derivatives increased with age in tissues of mice fed with a selenium-adequate diet.

[Futurist1000]

methionine

It is well established that many amino acid residues of proteins are susceptible to oxidation by various forms of reactive oxygen species (ROS), and that oxidatively modified proteins accumulate during aging, oxidative stress, and in a number of age-related diseases. Methionine residues and cysteine residues of proteins are particularly sensitive to oxidation by ROS. However, unlike oxidation of other amino acid residues, the oxidation of these sulfur amino acids is reversible. Oxidation of methionine residues leads to the formation of both R- and S-stereoisomers of methionine sulfoxide and most cells contain stereospecific methionine sulfoxide reductases that catalyze the thioredoxin-dependent reduction of MetO residues back to methionine residues. We summarize here results of studies, by many workers, showing that the methionine sulfoxide content of proteins increases with age in a number of different aging models, including replicative senescence and erythrocyte aging, but not in mouse tissues during aging. The change in levels of methionine sulfoxide may reflect alterations in any one or more of many different mechanisms, including (i) an increase in the rate of ROS generation; (ii) a decrease in the antioxidant capacity; (iii) a decrease in proteolytic activities that preferentially degrade oxidized proteins; or (iv) a decrease in the ability to convert methionine sulfoxide residues back to methionine residues, due either to a direct loss of methionine sulfoxide reductase enzyme levels or indirectly to a loss in the availability of the reducing equivalents (thioredoxin, thioredoxin reductase, NADPH generation) involved. The importance of methionine sulfoxide reductase activity is highlighted by the fact that aging is associated with a loss of methionine sulfoxide reductase activities in a number of animal tissues, and mutations in mice leading to a decrease in the Msr levels lead to a decrease in the maximum life span, whereas overexpression of methionine sulfoxide reductase leads to a dramatic increase in the maximum life span.

So methionine restriction probably leads to an decrease in methionine oxidation thus an increase in lifespan.

[niner]

Wow. Now there might be three ways to mimic CR without the gaunt look. CR mimetics, Intermittent Fasting, and now Methionine Restriction.

High levels of methionine can be found in sesame seeds, Brazil nuts, fish, meats, and some other plant seeds.  Most fruit and vegetables contain very little; however, some have significant amounts, such as spinach, potatoes, and boiled corn.  DL-methionine is sometimes added as an ingredient to pet foods.

So, be a slightly modified vegetarian and stay out of Rover's dish.