amino acid signaling
One of my readers questioned my recipe from “If Popeye Was a Real Man He Would Have Eaten Kale” and asked what I thought about the research linking longevity and methionine restriction. Eggs are a significant source of methionine and so perhaps could lead to faster aging. In order to answer this question, it’s important to consider the mechanisms involved and the evolutionary advantages. This question enters one of the world’s biggest rabbit holes and is too much for one posting so watch for posts related to methionine restriction and longevity in the future.
To review, several research studies have shown that dietary restriction of the essential amino acid, methionine, results in 42-44% increase in average life span of rats, mice and fruit flies. There are two major mechanisms that have been identified that contribute to this. One is lowered production of mitochondrial reactive oxygen species (mROS). These are basically free radicals produced in the mitochondria where our cells make energy or ATP. mROS speed up degeneration of mitochondrial DNA, ultimately leading to faster cell turnover and aging. Glutathione (GSH), is one of the most powerful reducers of mROS. GSH is made from methionine. However, restricting methionine intake results in elevated levels of GSH in all tissues except for the kidneys. How is it that restricting methionine, the one essential amino acid that is a precursor to glutathione, results in higher levels of glutathione? It’s going to be very interesting when researchers figure out the answer to the dichotomy.
With regards to longevity, I think methionine restriction has two contributing factors. I’ll discuss one of them here and leave the second for another time. Here is the first:
Since methionine is an essential amino acid and is present in all naturally-occurring protein sources, it likely acts as a signal for protein abundance or scarcity. Cellular signaling mechanisms are too involved for this discussion. To simplify I’ll just say signaling may directly due to the presence or absence of methionine or may be through a secondary metabolite like homocysteine. If its presence signals abundance, then the body would increase metabolism as it goes into an anabolic state preparing for reproduction. An increase in metabolism will always result in an elevation of all ROS in cells. This, by default, speeds cell turnover and aging. On the other hand, if protein intake, and thus methionine, is scarce then the body likely creates different signals that reduce metabolism. Reduced metabolism reduces turnover and aging of cells. This is the same mechanism through which caloric restriction is theorized to promote longevity.
With methionine, this control mechanism would incur an ultimate evolutionary survival advantage. We know that methionine restriction reduces fecundity (reproductive ability). During times of protein scarcity reduced metabolism via this signaling mechanism would minimize ongoing damage to mitochondrial and cellular DNA. This would help to preserve the potential for successful reproduction (passing on of genes) and to prolong existence in anticipation for a more abundant and auspicious time. As mentioned, in times of protein abundance, methionine would signal anabolism and preparation for reproduction. If an individual is past reproductive age, metabolism will still increase. In a community setting the increased vitality of older individuals would allow them to contribute more in the short term. In this situation, survival advantage would be incurred throught The Grandmother Hypothesis . It would also speed its ultimate demise, freeing up resources for the younger individuals who can still reproduce.
Since we, in the first world, live in a state of perpetual abundance we have time to figure out how we can live longer. Restricting dietary methionine may likely contribute to this. It seems logical that you would simply restrict foods that contain high amounts of methionine. However, it isn’t that straight forward. Next time I will discuss the glutathione dichotomy and methionine’s role in the alternation between Phase 1 and Phase 2 liver detoxification, the intricacies of dietary amino acid absorption, and research that contradicts the hypothesis that a vegan diet reduces methionine intake. Yes, the egg question will finally be answered.by