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Free radicals as respiratory distress signal


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I’ve been reading The Vital Question, a book by Nick Lane that explores the role of energy in the origin of life from alkaline hydrothermal vent to eukaryotes.  (There’s a 2 ½ minute video by the author on the linked page if you want a super quick summary.)  In the last chapter, he looks at the free-radical theory and tries to explain why “Taking high-dose antioxidant supplements carries a modest but consistent risk.”  It has been shown that blocking free-radical signals with antioxidants can block ATP synthesis in cell cultures.  It is likely that free-radical signals optimize respiration in mitochondria by increasing the number of respiratory complexes which increases respiratory capacity which leads to more ATP.  Antioxidants suppress the trigger of this mitochondrial biogenesis causing the increase in free radicals to be ignored by the cell.  He proposes a “death limit” of free radicals above which the cell commits apoptosis.

“Free radicals signal the problem that respiratory capacity is low, relative to demand.  If the problem can be fixed by making more respiratory complexes, raising respiratory capacity, then all is well and good.  If that does not fix the problem, the cell kills itself, removing the presumably defective [mitochondrial] DNA from the mix.”

A subsequent paragraph states that there is no simple relationship between rate of living and free-radical leak:

“When you exercise, you consume more oxygen, so your free-radical leak rises, right?  Wrong.  It remains similar or even goes down because the proportion of radicals leaked relative to oxygen consumed falls off considerably.”

That is summarized in a diagram labeled Why rest is bad for you.


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  • 3 months later...

Just started reading my first book by Nick - Transformer. While the style of the text is not mine the depth of things are very impressive. I think the lack of "dynamic" or "weight coefficients" or "math thinking" is the main problem of normal textbooks (on cell biology and all related) used for selftraining.

For me the idea of a "flux" that is created by a specific property of membranes that permits only some specific things to pass into a very complicated "fabric" that will manage this flux at sometimes hard to imagine rates and efficiencies, transforming molecules through the different possible pathways is something I thought of but was unable to coin myself. And the way of things working that allows materia to follow different paths, depending on interruptive things (the "pressure" in this flux, presence/abscence or even gradients in concentrations of other molecules or charges) as a possible explanation of failures to tackle some things (like most cancers and "aging effects") for decades is a very elegant way to use Occam's razor and do not create exotic explanations and false expectations that a single molecule (or e.g. 10 of them working in synergy) can do a significant life expansion effect. Offcourse the last statement is just IMHO, in such a topic it is very easy to be wrong and is very hard to guess right even about a small piece of how the things really works.

There are also interesting videos by Nick on youtube, so for those who like good popular science I recommend to add Nick to the queue of read/watch.





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