Autophagy Required For Calorie Restriction Benefits?
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Today, I noticed a new paper on the relationship between the demonstrated health benefits of calorie restriction and autophagy, the process by which cells recycle damaged organelles (such as the increasingly important mitochondria) and other components. More efficient autophagy is generally considered to be a good thing for all the obvious quality control reasons - newly created, functional cellular components are better than old, malfunctioning cellular components.

Autophagy is Required for Dietary Restriction-Mediated Life Span Extension in C. elegans:

Dietary restriction extends life span in diverse species including Caenorhabditis elegans. However, the downstream cellular targets regulated by dietary restriction are largely unknown. Autophagy, an evolutionary conserved lysosomal degradation pathway, is induced under starvation conditions and regulates life span in insulin signaling C. elegans mutants. We now report that two essential autophagy genes (bec-1 and Ce-atg7) are required for the longevity phenotype of the C. elegans dietary restriction mutant (eat-2(ad1113) animals. Thus, we propose that autophagy mediates the effect, not only of insulin signaling, but also of dietary restriction on the regulation of C. elegans life span. Since autophagy and longevity control are highly conserved from C. elegans to mammals, a similar role for autophagy in dietary restriction-mediated life span extension may also exist in mammals.

The work is in nematodes rather than people, but most interesting. If you look back into the Longevity Meme archives, you'll see a few references to calorie restriction and autophagy in mammals. The focus there was to understand to what degree increased autophagy causes the health and longevity benefits of calorie restriction - such as by culling the numbers of damaged mitochondria and thus reducing their deleterious effect on the rest of the body:

I believe this is the first I've seen of the suggestion that autophagy is strictly necessary for the benefits of calorie restriction in any way. One can speculate as to whether that raises the profile of the role of mitochondrial damage in age-related disease and degeneration - but there's a lot more research yet to be done here.

Fortunately, research groups around the world are converging on the biochemistry of calorie restriction from all sorts of directions: autophagy; sirtuins; other likely pathways; the immune system; studies in worms, flies, mice, monkeys and people. Today's mysteries won't last much past 2012, I'd wager - a lot of money is flowing into this field.

Comments

This does well to show how there is a relation, but I think it needs to be established how it is not an all-encompassing panacea. The destruction of old cells and replacement of them with new ones is good if bad dies and the new are spawned from the good undamaged cells. It is plausible though that good cells could die, and bad cells may be the ones to increase their replication to reproduce them once the cell is anabolic once more.

The main issue is to figure out if there are any preferential regulatory mechanisms in the cell that make the new replacement cells gravitate to be drawn from healthy cells than from unhealthy ones. I'm wondering if someone has an idea about this, as I am unfamiliar with the means by which the organelles regenerate their numbers.

Posted by: Tyciol at October 30, 2007 10:34 AM
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