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

Jul 31, 2017 1h 10m 17 insights
<p><strong>Dr. Guido Kroemer</strong></p> <p>Dr. Guido Kroemer is a professor at the University of Paris Descartes and an expert in immunology, cancer biology, aging, and autophagy.</p> <p>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.</p> <p><span style="font-weight: 400;">In this episode, you'll discover: </span></p> <ul> <li><strong>(00:00)</strong> Introduction</li> <li><strong>(09:09)</strong> The three main nutrient signals that activate autophagy</li> <li><strong>(20:55)</strong> The role of fasting and nutrient deprivation in autophagy</li> <li><strong>(28:52)</strong> Exercise induces autography </li> <li><strong>(33:07)</strong> Autophagy cleans out damaged organelles</li> <li><strong>(35:14)</strong> Mitophagy keeps mitochondria healthy</li> <li><strong>(39:38)</strong> Autophagy clears away neurodegenerative proteins in the brain</li> <li><strong>(48:29)</strong> Autophagy in cancer is a double-edged sword</li> <li><strong>(54:52)</strong> Fasting mimetics (e.g., resveratrol, spermidine, hydroxycitrate) induce autophagy</li> </ul> <p><span style="font-weight: 400;">If you're interested in learning more, you can read the <a href="https://www.foundmyfitness.com/episodes/guido-kroemer">full show notes here</a>.</span></p> <p><span style="font-weight: 400;">Join over 300,000 people and get the latest distilled information on fasting & caloric restriction straight to your inbox weekly:</span> <span style="font-weight: 400;"><a href="https://www.foundmyfitness.com/newsletter">https://www.foundmyfitness.com/newsletter</a></span></p> <p><span style="font-weight: 400;">Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more:</span> <a href="https://www.foundmyfitness.com/crowdsponsor"><span style="font-weight: 400;">https://www.foundmyfitness.com/crowdsponsor</span></a></p>
Actionable Insights

1. Prolonged Fast for Autophagy

Engage in a prolonged fast of three to five days (water, coffee/tea without sugar/milk) for robust autophagy induction. This duration has been shown to cause “massive induction of autophagy” in human circulating leukocytes and can lead to cell regeneration.

2. Practice Intermittent Fasting

Implement intermittent fasting regimens, such as eating within an 8-10 hour window daily or fasting completely for one day followed by normal nutrition. In mice, this approach extended lifespan similarly to caloric restriction and helped manage weight.

3. Induce Autophagy with Exercise

Incorporate regular exercise, including aerobic, eccentric, and concentric types, into your routine. Exercise is known to induce autophagy in skeletal muscle in humans and mediates anti-obesity and anti-diabetic effects dependent on autophagy in mice.

4. Consume Coffee for Autophagy

Drink coffee, whether caffeinated or decaffeinated, as its polyphenols can magnificently induce autophagy. Regular coffee consumption has also been linked to a reduction in cardiovascular and neurodegenerative diseases.

5. Restrict Protein to Reduce mTOR

Limit your protein intake to reduce the activation of IGF-1 and mTOR. This reduction is associated with the induction of autophagy, a process important for cellular cleanup.

6. Eat Spermidine-Rich Foods

Increase your intake of spermidine by consuming foods like natto, durian fruit, fermented cheese (from non-pasteurized sources), and certain vegetables. Spermidine is a natural compound that can induce autophagy.

7. Manipulate Gut Microbiome

Explore ways to manipulate your gut microbiome, potentially via specific probiotics, to increase its production of polyamines like spermidine. This manipulation may help reduce colon cancer development and aging.

8. Utilize Fasting Mimetics

Consider using specific fasting mimetics like hydroxycitrate, spermidine, and resveratrol. These compounds can induce autophagy by modulating key signaling pathways, potentially mimicking the benefits of fasting and caloric restriction.

9. Inhibit Acetyl-CoA Generation

Use hydroxycitrate or other pharmacological compounds that inhibit ATP citrate lyase. This action depletes acetyl-CoA, leading to deacetylation and autophagy, mimicking caloric restriction.

10. Utilize Spermidine or C6

Consider using spermidine (a natural compound) or C6 (a pharmacological compound) as specific inhibitors of EP300. These compounds cause deacetylation and autophagy, mimicking caloric restriction.

11. Consume Resveratrol

Consume resveratrol, found in red wine, as it activates deacetylases. This activation causes hypoacetylation and autophagy, mimicking caloric restriction.

12. One Meal a Day (OMAD) Routine

Adopt a one-meal-a-day pattern, specifically having dinner with cheese and wine, as personally practiced by Dr. Cromer. This combines spermidine (from cheese) and resveratrol (from wine) for a synergistic effect on autophagy.

13. Five-Day Fast Twice Yearly

Practice a five-day prolonged fast twice a year, as personally done by Dr. Cromer. This is a more intense fasting regimen for potential health benefits.

14. Limit Glucose During Infection

When experiencing a bacterial infection, avoid force-feeding or increasing glucose levels. Not eating during infection is a protective mechanism that helps avoid excessive inflammation and can prevent the infection from becoming lethal.

15. Stimulate Autophagy for Neuroprotection

Stimulate general autophagy through methods like starvation or biochemical mimetics. This is a theoretical strategy to increase autophagic turnover and reduce toxic protein aggregates associated with neurodegenerative diseases.

16. Combine CR Mimetics with Chemo

For cancer treatment, combine chemotherapy with caloric restriction mimetics such as spermidine, hydroxycitrate, and resveratrol. This combination can enhance the anti-cancer immune response, making the therapy more durable and effective.

17. Enhance Learning with Video

If you find the scientific concepts challenging, watch the accompanying video on YouTube. The video provides definitions of scientific terms and figures, serving as a good resource for learning more about autophagy.