Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation

Posted on July 31st 2017 (over 1 year)

Dr. Guido Kroemer is a professor at the University of Paris Descartes and an expert in immunology, cancer biology, aging, and autophagy. He is one of the most highly cited authors in the field of cell biology and was the most highly cited cell biologist for the period between 2007 and 2013. Especially notable among his contributions: he was the first to discover that the permeabilization of mitochondrial membranes is a concrete step towards apoptotic cell death.

This episode is decidedly focused on autophagy, an important cellular program that is inducible by dietary fasting and has broad implications for aging and cancer. Autophagy discussion includes: 

  • 00:04:44 - How the 3 main signals that activate autophagy all involve nutrient sensing. 
  • 00:16:30 - The role of different types of fasting and nutrient deprivation in autophagy. 
  • 00:24:35 - How different types of exercise can induce autophagy. 
  • 00:32:04 - How a specific type of autophagy called mitophagy keeps mitochondria healthy. 
  • 00:33:07 - How autophagy has been shown to slow cellular aging.
  • 00:35:13 - How autophagy prevents neurodegenerative diseases by clearing away protein aggregates. 
  • 00:44:04 - The role of autophagy in cancer as a possible double-edged sword. 
  • 00:50:27 - How certain compounds known as caloric restriction mimetics (or fasting mimetics) including resveratrol, spermidine, hydroxycitrate can induce autophagy by tricking the cell through the modulation of one or more of the 3 main autophagy signaling pathways.

Learn more about Dr. Guido Kroemer

TL;DR

Fasting Autophagy

Nutrient deprivation → ↑ Protein Deacetylation (↓ cytosolic Acetyl CoA) + ↓ mTOR + ↑ AMP Kinase → Autophagy

Hydroxy Citrate Autophagy

↓ ATP citrate lyase activity → ↓ Protein Acetylation → Autophagy

Spermidine Autophagy

↓ Acetyltransferase activity (especially EP300) → ↓ Protein Acetylation → Autophagy

Resveratrol Autophagy

↑ Detacetylase activity (especially SIRT1) → ↓ Protein Acetylation → Autophagy

... and... more generally...

↑ Protein Deacetylation → Autophagy

The relationship between cancer and autophagy is complex...

↓ tumor suppressor gene activity → ↓ autophagy → survival of pre-malignant cells → ↑ autophagy as a malignant adaptation​​​​​​​

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