Full question: In C. elegans, why does knock-down of cco-1 via RNA interference in specific tissues like body wall muscle decreases life span, whereas knock-down in the nervous system and intestine increases life-span?


Also from paper 'The Cell-Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity'

Supposedly, it's through hormesis. But why is there a differential effect from tissue to tissue?


Let us first answer the question: what is the effect of cco-1 knock-down in C. elegans. Durieux J., Wolff S. and Dillin A. in their paper "The cell-non-autonomous nature of electron transport chain-mediated longevity". Cell 144:79-91 (2011) provide the following explanation:

The life span of C. elegans can be increased via reduced function of the mitochondria; however, the extent to which mitochondrial alteration in a single, distinct tissue may influence aging in the whole organism remains unknown.

So, by slowing-down the mitochondria function you manage to slow-down the normal wear-and-tear of the mitochondrial enzymes, which are normally responsible for the so-called respiratory chain -- one of the fundamental biological process for storing energy in cells (despite the common belief, ATP is rarely to store energy, but mostly to transfer it to the target!).

If we group the tissues where the knock-down leads to similar effects we will get muscle cells opposed by neurons and intenstine cells.

This is just my suggestion, but if we approach those groups with the idea of energy storage and re-use in mind, we'll see that muscle cells have much higher turnover of energy (for contraction and even more for dilation), whereas nerve and intestine cells are not that dependent upon energy and have much lower baseline of energy consumption and turnover.

Now we can suggest that cco-1 knock-down decreases the functions of mitochondria in muscle cells below the acceptable level and the decreased life span is due to depletion of mitochondrial energy storage under light stress conditions which would have been easily coped with under normal conditions. And vice versa, nervous/intenstine cells requiring a constant energy source at a much lower level just help the animal to cope with stress more effectively even during old age, leading to increased life span.


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