The Importance of Autophagy for Mitochondria

Mitochondria are the powerplants of the cell, bacteria-like entities that produce chemical stores of energy to power cellular processes. The accumulation of damaged mitochondria is thought to cause a fair portion of degenerative aging, and differences in the ability of mitochondria to resist damage appear to play an important role in determining variation in life span between similar species.

Autophagy is one of the processes by which damaged mitochondria are removed from consideration, in this case by destroying them and freeing up the materials for recycling. Autophagy also removes other damaged cell components and unwanted metabolic byproducts. Mitochondria-specific autophagy is often called mitophagy or macromitophagy, and a large pile of evidence suggests that it is this aspect of autophagy that is most responsible for the association between increased levels of autophagy and increased longevity in a range of laboratory species and different methods of life extension.

At some point in the near future, development will be underway in earnest on drugs to boost autophagy. Here researchers add more evidence to considerations of autophagy and longevity while examining mitophagy in yeast under calorie restriction (CR), a well-known method of life extension:

In this study, we provide the first evidence that selective macroautophagic mitochondrial removal plays a pivotal role in longevity extension by a CR diet in chronologically aging yeast; such a diet was implemented by culturing yeast cells in a nutrient-rich medium initially containing low (0.2%) concentration of glucose, a fermentable carbon source. It should be emphasized that under these longevity-extending CR conditions yeast cells are not starving but undergo an extensive remodeling of their metabolism in order to match the level of ATP produced under longevity-shortening non-CR conditions.

Moreover, our study also reveals that in chronologically aging yeast limited in calorie supply macromitophagy is essential for longevity extension by LCA. This bile acid is a potent anti-aging intervention previously shown to act in synergy with CR to enable a significant further extension of yeast lifespan under CR conditions by modulating so-called "housekeeping" longevity pathways.

In sum, these findings imply that macromitophagy is a longevity assurance process that in chronologically aging yeast underlies the synergistic beneficial effects of anti-aging dietary and pharmacological interventions (i.e., CR and LCA) on lifespan. Our data suggest that macromitophagy can maintain survival of chronologically aging yeast limited in calorie supply by controlling a compendium of vital cellular processes known for their essential roles in defining longevity. [It] is conceivable that in chronologically aging yeast limited in calorie supply macromitophagy selectively eliminates dysfunctional mitochondria impaired in vital mitochondrial functions that define longevity.



I have done a bit of research on autophagy and while it does appear promising I have been unable to find any scientific research or consensus out there on what is the optimal fasting schedule for humans. Intermittent (18 hours or so), 24 or 48 hours fasting, week-long fasting?

Posted by: rum_runner at April 3rd, 2013 11:38 AM

@rum_runner: So far as I know, correct, there is no consensus - not even in animal studies of intermittent fasting. The amount of research on intermittent fasting is small compared to that on straight calorie restriction, so expect to see less certainty on any topic relating to it.

Posted by: Reason at April 3rd, 2013 12:28 PM

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