Autophagy on the brain

Ouroboros walks us through the case for autophagy turning from good to bad as we age: "Previously, we've discussed autophagy as being on the side of the angels in the fight against cellular deterioration ... A new article in BioEssays [reviews] the evidence that in C. elegans, autophagy is responsible for the ultimate demise of neurons - the last holdouts against age-related decline, and themselves responsible for many aspects of genetic control of lifespan. ... Which is not to say that we should throw the autophagic baby out with the bathwater. It's quite conceivable that tissue targeting, timing of treatments, and other steps could be taken in order to make interventions based on autophagy an effective way to treat age-related decline. Rather, this is a reminder that too much of a good thing can be bad for you, and that autophagy is not always an angel. The devil is (as always) in the details."

Let us for the moment accept the idea that autophagy is an anti-aging force in mid-life, per the articles cited in the intro paragraph of this posting, but a pro-death force in late life, per the neuronal death mechanism described in the paper. (Antagonistic pleiotropy, anyone?)

By the former premise, it’s tempting to think that in order to decrease age-related accumulation of cellular trash, we ought to increase autophagy (by CR, CR mimetics, anti-lipolytic drugs, or some other pharmaceutical mechanism) — however, by the latter premise, broad acceleration of autophagy could have deleterious consequences on the nervous system via activation of cell death pathways. (”We have some good news and bad news: You have the heart of a sixteen-year-old, but a brain made out of swiss cheese.”)

Which is not to say that we should throw the autophagic baby out with the bathwater. It’s quite conceivable that tissue targeting, timing of treatments, and other steps could be taken in order to make interventions based on autophagy an effective way to treat age-related decline.

Rather, this is a reminder that too much of a good thing can be bad for you, and that autophagy is not always an angel. The devil is (as always) in the details.

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