Autophagy:
Why you should eat yourself

by Eric Drexler on 2010/07/24

I’d like to say a few words about one of the hottest and, in my view, most important areas in biomedicine: autophagy, a process crucial to health, disease, and aging. Autophagy research is expanding rapidly.

In autophagy (“self eating”), cells engulf and digest their own macromolecules and organelles. Autophagy serves two functions: providing critical nutrients in times of scarcity, and recycling damaged cellular structures (2009 review, pdf).

It seems that lab animals and human beings fed ad-libitum do too little autophagic recycling. The resulting accumulation of damaged machinery causes a wide range of functional deficits, and accumulation of damaged mitochondria, in particular, increases the production of reactive oxygen species, accelerating further damage.

In a range of organisms, dietary restriction both induces autophagy and results in wide-ranging health benefits, including the extension of healthy lifespans. Blocking autophagy blocks the most important of these effects. Rapamycin induces autophagy and extends lifespan, as does sirtuin-1. Autophagy again appears to be central to these effects. A recent review article examines genetic interventions that indicate “tight connections between autophagy, health span and aging”.

The importance of vigorous autophagy to human lifespan is an inference, but it’s more than just plausible. Diverse results in humans, mice, and C. elegans: they all fit a pattern of effects that stems from a process as old as eukaryotic cells.

Upregulating autophagy has known, wide-ranging benefits, and more are being discovered at a fast pace. You might enjoy exploring the state of current knowledge with Google Scholar (here’s a search).

Let’s see… a July, 2010 opinion from Trends in Molecular Medicine: “Autophagy as a basis for the health-promoting effects of vitamin D”. That’s a new link to another hot topic.


See also:

{ 7 comments… read them below or add one }

William L. Dye ("willdye") July 27, 2010 at 6:42 am UTC

Thank you for yet another interesting and informative post. For what it’s worth, it seems counterintuitive to me that natural selection would favor organisms which consistently failed in their efforts to acquire all of the food that they wanted. The evidence is clear, however, that my intuition is once again quite wrong.

The phenomenon seems more intuitive to me when I think of this pattern: if we follow our natural inclinations, most of us exercise less than we should, eat more than we should, stay up later and sleep longer than we should (on approximately a 26-hour cycle), consume more sweets and fats than we should, think less critically of our own ideas than we should, and in general exceed the proper dosage of things that are usually good for us as long as we don’t get quite as much as we want. It’s easy enough to come up with a speculative reason for any one of these observations, but not nearly as easy to design a satisfying, repeatable experiment to confirm the speculation.

For now maybe it’s better for me to avoid formulating explanations just yet, and instead emphasize simply observing the bigger pattern more clearly. Is there some connection between caloric restriction and at least some of the other instances in which “as much as we want” is too much?

Bah. Appropriately, I’ve stayed up too late. I’m so tired that all I can think of right now are bumper stickers:

“Autophagy — bite me, me!”

“Life sucks — and that’s a good thing”

“Dad was right — it builds character”

“Caloric restriction: extending life by enjoying it less”

Perhaps after some sleep, some coffee, and an overly large breakfast I’ll be better suited for such speculation. Then again, I have some new video games to try out, and with a relaxed schedule tomorrow I can sit down and play as much as I want. As much as I want…

Eniac July 28, 2010 at 3:14 am UTC

Telomeres and anioxidants are so passe. Long live autophagy!

Samantha Atkins July 30, 2010 at 6:09 am UTC

So what would tend to trigger this sufficiently? Is it worthwhile to fast one day a week or part of the day?

William L. Dye ("willdye") August 5, 2010 at 4:59 am UTC

Samantha: The bottom line is that it’s too soon to say, especially in the case of humans. I expect that there will be controversy on that question for quite some time. The Wikipedia article on Caloric Restriction discusses the issue in non-technical terms (near the bottom, under the title “Intermittent fasting”), and includes links to some of the more technical medical articles.

Frank Taeger August 30, 2010 at 6:59 pm UTC

@ Samantha : Short term fasting (24-48 hours) has been shown by experiments at the University of Florida to induce autophagy.

Eric Drexler September 2, 2010 at 3:00 am UTC

@ Samantha, Frank — Ketogenic diets also induce autophagy. They are also strongly neuroprotective (papers here and here), which I think is likely to involve the neuroprotective role of autophagy.

EinRand September 8, 2012 at 1:07 pm UTC

Excellent post Mr. Drexler,
As a practical matter, most would not practice IF because fasting is ‘felt’ to be too draconian, thus big pharma seeks patentable pill.

Alternative: First change to low carb. (no sugar) diet. Not having to undergo swings in insulin greatly affects learning to distinguish emotional from physiological hunger. At least a three day challenge.

Second, practice intermittent fasting (8 to 22 hours) using electrolyte replacement (i.e. Magnesium, Potassium, and Sodium). Seventy calories (vegetable juice + electrolytes) twice per a day is not enough to stop ketosis.

These transitions are difficult and can take time. Going zero sugar is tantamount to cold turkey sobriety for some. Given the incidence of ‘diseases of western civilization’, waiting for pharma to manufacture a $10/d pill and the knowledge of our own imminent mortality is reason enough to read Gary Taubes and Robert Lustig.

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