Ahh…AUTOPHAGY.  Autophagy is another one of those terms that everyone cavalierly throws around without any real understanding of what it means…but we know “autophagy is good.”  It’s sort of the opposite of the word “fascist,” which everyone seems to use as an insult, not because we really know what that means, but because “fascism is bad.” 

The word autophagy literally means “self-eating.”  And there are many types of autophagy; there is macroautophagy, microautophagy, chaperone-mediated autophagy, mitophagy, tacophagy (just kidding, it’s probably not in your body’s best interest to eat tacos all the time).  But autophagy basically boils down to CELLULAR HOUSEKEEPING.  Cells get old and little messes start to accumulate, so it’s best to recycle some of the damaged proteins to keep your physiologic abode in a general state of orderliness.  And this process involves the lyososome and a swath of cool proteins with names like Beclin-2, GATOR1, and Ragulator. 

Anyway, autophagy is the preferred method of housekeeping in contrast to APOPTOSIS.  Because when cells become problematically dysfunctional and commit suicide, they leave a swath of pro-inflammatory mediators in their wake. 

Essentially, if you have a small mess in your house, you clean things up, take out the garbage, and prevent a ton of junk from accumulating.  And this requires a consistently “clean” lifestyle; that’s autophagy.  Conversely, if big-time messes accumulate and vermin start running roughshod amid the heaps of debris, then you might have to completely set fire to your condemned habitation.  That’s apoptosis. 

So what sort of things promote autophagy?  Exercise.  Fasting.  Not being in a chronic state of overnutrition.  Can we measure autophagy?  Not really.  But we do know that autophagy is regulated by two main nutrient sensors called AMPK and mTOR.  AMPK is relatively dominant in states when the cellular AMP to ATP ratio is elevated…this would be when exercising or fasting.  Conversely, insulin and nutrient availability are potent activators of mTOR, particularly mTORC1, which is an anabolic pathway. 

However, these nutrient sensors are not binary switches that are either “on or off.”  They are either more relatively dominant or relatively less active depending on the context, and this can even vary depending on the tissue or organ system involved.  For instance, you can activate mTORC1 in skeletal muscle simply by performing resistance exercise, although AMPK may be simultaneously dominant in the liver.  It’s complicated.

Our bodies are meant to cycle between fasting and fed states.  And when we do that, the balance between autophagy and anabolism tends to work out just fine.  So should you take your favorite “autophagy activator” like Rapamycin?  By all means, you absolutely should if you’re a worm indigenous to Easter Island. 

But I’m not optimistic that any therapeutic can ever take the place of the following:

• Sleep
• Don’t eat crap
• Move
• Cycle between fasting and fed states

Control your insulin, control your life…and I think you “control your autophagy” as well.