Autophagy isn’t a big deal in the way some Internet Bro’s think it is. Yes, Dr Ohsumi received a Nobel Prize for cracking deeply into this nut, but that in no way means “intermittent fasting is awesome because autophagy.” Autophagy isn’t awesome like that.

Alternate title: The dark side of autophagy.

For example: Autophagy contributes to muscle wasting in cancer cachexia (Penna et al., 2013)

Cachexia (muscle wasting) is one of the leading contributors to poor quality of life in cancer patients. Thanks, autophagy.

“Autophagy is the major process for degradation of cellular constituents, its rate being enhanced under stress conditions leading to organelle damage…”

Fasting/starvation: muscle breaks down to provide amino acids for gluconeogenesis mediated in part, via autophagy. This slows as starvation proceeds due to the muscle-sparing effect of fat-derived fuels (ie, starvation ketosis), but it still happens. If it didn’t, we wouldn’t survive very long without food. However, autophagy increases as starvation proceeds, but the rate of muscle breakdown declines… O_o

maybe this is where the “clearing of cellular debris” kicks in?

what does that even mean [rhetorical]

“autophagy has been shown to contribute to starvation-induced muscle atrophy” … “autophagy-related genes have been shown to be induced in muscle by fasting” … “autophagic degradation induced by starvation is sufficient to determine muscle depletion, even if the ubiquitin-proteasome degradation is blocked using pharmacologic or genetic approaches.” (Penna et al., 2013)

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteosome (Sanndri 2013)

^^^ THIS FIGURE

Some people feel better with brief periods of intermittent fasting. My question: what is the evidence this is due to increased autophagy? some rodent studies?

why not something else, like BDNF or Sirtuins or one of the FGFs [or something else]?









Part II. Autophagy regulates adipose mass and differentiation in mice (Singh et al., 2009). Tl;dr: decreased autophagy = lean mice.

In adipose tissue at least, this is confirmed in human studies (eg, see Kovsan et al., 2010, Jansen et al., 2012, & Nunez et al., 2013).

Exercise is the strongest autophagy-inducer I know of. Exercise is good, so this must mean autophagy is also good, right? No, that is faulty logic.

Fasting promotes neuronal autophagy in rodents (Alirezaei et al., 2010), but again, is this something we should be trying to maximize? Maybe not (eg, see Jaroonwitchawan et al., 2016 and Zhao et al., 2016).

I’m not saying autophagy per se is good or bad. Autophagy is a biological process that happens in a variety of #contexts; the Nobel Prize doesn’t mean it will give you miraculous health or in any way support prolonged fasting… too many known and unknown unknowns

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