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Recommended reading:
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A newly-published call-to-arms and technical exposition on the SENS approach to age-related disease
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An early study of one of the seven targets of SENS research
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What to do in the meantime:
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Full of diet and lifestyle tips based on current science, to preserve your health until better technology is developed
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MitoSENS:
Evolutionary Questions
Before animals and plants split off, a bacterium infected a eukaryotic cell. Neither killed the other, but the bacterium gave the host cell a new source of energy, ATP, which provided an evolutionary advantage. To add to the symbiosis, over time eukaryotes expressed more and more of this bacterium's DNA inside its own nucleus, safe from the free radical byproducts of ATP production.
As these bacteria evolved into mitochondria, most (about a thousand) of their genes made the jump to the safety of the nucleus. However, 13 didn't. That they haven't is particularly interesting since not only would they not be subjected to free radicals associated with ATP production, but also would benefit from the more numerous DNA repair mechanisms available. The aim of researchers at MitoSENS is to do what evolution hasn't, at least not in mammals, and maintain functioning versions of those 13 genes in the safer environment of the nucleus.
More than side effects, expressibility seems to be the reason mammals haven't evolved nuclear expression of mtDNA. Translating the circular single-strand code of bacteria into double helix format is not researchers' big concern though. Instead, there is a quality all 13 of these genes have in common which seems to be the evolutionary obstacle.
Each of the 13 proteins for which these genes code is extremely hydrophobic: they don't dissolve well in water. So if they were to be expressed from nuclear DNA, they couldn't get from the cytosol through the mitochondrial membrane to aid in ATP production. They would aggregate too much to permeate the membrane. Hydrophobicity may therefore be the one big obstacle to obviating the consequences of damaged mitochondrial DNA (mtDNA).
Researchers have started borrowing ideas from microbes that do express analogues of at least some of these 13 proteins from their nuclei. Their nuclear genes attach compounds to the non-functioning parts of the hydrophobic proteins to enable solubility, so they don't clump before being absorbed into the mitochondrion.
This strategy has been successfully attempted in mammalian mitochondria for at least one of the 13 genes. (To date, at least three of the 13 proteins have, in vitro, been expressed from the nucleus and shown to function within the mitochondrion.)
Side effects seem to go hand in hand with the expressibility question. For example, aggregation of mitochondrial proteins can lead to cell death.
It may be that if hydrophobicity is overcome, any significant side effects will be resolved as well. Whether it is so simple of course needs to be explored in vivo.
Encouragingly the degree of the hydrophobicity these proteins have in common suggests there may be no significant side effects selected against in mammals other than those related to hydrophobicity. Further arguments can be found here.
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