When people talk about fasting and autophagy, they usually talk about molecular pathways such as AMPK and when they talk about obesity or cancer, they talk about mTOR. What is usually (wrongly) interpreted is the following:

AMPK = Health and longevity.
mTOR = Disease and aging

This is due to a poor understanding of how our physiology and homeostasis works and is a dangerous reductionism for the absolutist.

AMPK is a protein complex activated especially when we exercise, fasting or with low glucose availability. AMPK has been shown to be beneficial in ameliorating obesity and in relation to metabolic complications in skeletal muscle. AMPK is a known cell energy sensor as we all know.

Briefly, just to say that activation of AMPK promotes better enzyme expression and activation of skeletal muscle oxidative metabolism, something that as we know is very limited in pathological obese subjects.

However, like everything else in our physiology it responds to an almost perfect balance. There is nothing bad and nothing good in our organism, everything is necessary in its right measure. Over activation of AMPK precisely leads to worsening of health, increased aging, cellular senescence, neurodegeneration and may even increase insulin resistance (Sung et al 2011; Jiang et al 2013; Park et al 2014; Wang et al 2003).

mTOR is activated with high nutrient availability, counter to AMPK. However, low mTOR activity leads to problems with cell regeneration, growth, muscle development, sarcopenia, cachexia, hypercatabolism or neuromuscular problems (Zhang et al., 2019; Baraldo et al., 2020). Conversely, overactivation of mTOR, leads to pathological states, cancer, neurodegeneration, sarcopenia, etc.

Decreased autophagy leads to the same problems as mTOR overactivation, but it is that excessive autophagy activation leads to the same problems as mTOR underactivation!

What do I mean by all this? “Neither too much, nor too little”, “the good, if brief is twice as good”, “in the dose is the poison”… Well, a few words are enough for the wise man.

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