Autophagy expert: Dr. Guido Kroemer's personal take on fasting, eating and other lifestyle habits
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Several lifestyle behaviors have been shown to induce autophagy, including exercise, fasting, and dietary intake of so-called caloric restriction mimetics – compounds that “trick” cells into inducing autophagy even in the setting of sufficient nutrient levels. Examples of caloric restriction mimetics include resveratrol, which is found in red wine, and spermidine, which is found in cheese. In this clip, Dr. Guido Kroemer describes the autophagy-inducing behaviors he practices as part of his healthy lifestyle.
- Rhonda: Do you have any practices that you do? Do you, for example, do intermittent fasting or any type of fasting or time-restricted eating?
- Dr. Kroemer: So, usually in my ordinary life, when I'm in Paris and working, I only have one meal per day. So I have dinner with cheese and wine containing spermidine and resveratrol. It's an ideal combination because inhibiting the acetyltransferase and activating the deacetylase will have, of course, a synergistic effect.
- Rhonda: Oh, you do?
- Dr. Kroemer: Well, if you can show this in mice and this is an excuse for me to...
- Rhonda: Yeah, wine and cheese go great together.
- Dr. Kroemer: ...profit from a banquet combination. And I do also practice some fasting twice per year also when I don't eat anything for five days.
- Rhonda: Oh, wow. So you do a prolonged fast twice a year.
- Dr. Kroemer: Well, it's not so prolonged, so you know that Gandhi, for instance, has been doing fasting exercises for 20 days or more, which is the time at which a normal individual could have some long-term consequences on the health. So, 20 days is some period that usually is could be easily supported by a healthy middle-aged individual that has no underlying pathologies.
- Rhonda: I have a couple of friends that have done. One of them is used to very prolonged fast, like 20 days. He's morbidly obese, and he's lost now like 200 pounds over the course of a year by doing just several rounds of these prolonged fasts. But he's got a lot of fat, you know, to supply energy. I'm not sure I would still subject myself to a 20-day water fast, but it's cool to know that you do these five-day water fast, twice a year, and eating one meal a day.
- Dr. Kroemer: Yeah, and doing exercise.
- Rhonda: And doing exercise. And when you're eating... Sorry, throughout the day, when you're not eating, do you drink coffee?
- Dr. Kroemer: Yes.
- Rhonda: And there's polyphenols in coffee that actually...
- Dr. Kroemer: Yes, we published a study in mice giving them a non-toxic dose of caffeinated or decaffeinated coffee with a drinking water continuously. And we could show that this was magnificently inducing autophagy. Like caffeine independent fasting.
- Rhonda: Right, totally independent caffeine, so just the polyphenols. And this was like, I think, I read your study, it was like after four hours or something in the mice. So, in humans, potentially, maybe the fasting plus the coffee...
- Dr. Kroemer: Well, coffee abuse has been linked to major health-promoting effects. So, most cardiovascular and neurodegenerative diseases are actually reduced in heavy coffee drinkers as an independent link between lifestyle and pathology. So, of course, it's an association that obviously can be criticized because it's just a study in which you find a statistical correlation. It would be much more interesting to do a randomized clinical trial on coffee intake.
- Rhonda: More interesting and more expensive, yeah.
- Dr. Kroemer: Yeah. Absolutely.
- Rhonda: Great. So fasting, coffee, wine and cheese, one meal, exercise, you're doing it all. Awesome.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
A large class of diseases that involve the heart or blood vessels, including stroke, hypertension, thrombosis, heart failure, atherosclerosis, and more. Cardiovascular disease is often caused by lifestyle factors. As such, up to 90 percent of cardiovascular disease may be preventable.[1]
A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:
- Time-restricted eating
- Alternate-day fasting
- Periodic fasting (multi-day)
A broad range of disorders caused by the progressive death of neurons in the central and peripheral nervous systems. Common neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington’s disease, and multiple sclerosis. Although treatments are available for some neurodegenerative diseases, there are currently no cures.
A class of chemical compounds produced in plants in response to stressors. Polyphenols contribute to the bitterness, astringency, color, flavor, and fragrance of many fruits and vegetables. They often serve as deterrents to insect or herbivore consumption. When consumed in the human diet, polyphenols exert many health benefits and may offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. Dietary sources of polyphenols include grapes, apples, pears, cherries, and berries, which provide as much as 200 to 300 mg polyphenols per 100 grams fresh weight.
A chemical reaction that removes an acetyl functional group from a chemical compound. The presence of the acetyl functional group plays an important role in the synthesis, stability and localization of about 85% of human proteins.[1] During fasting, falling acetyl CoA levels in the cytosol initiate protein deacetylation and initiates autophagy. In general, protein deacetylation, whether from so-called caloric restriction mimetics or nutrient deprivation, is an important general inducer of autophagy.
- ^ Arnesen, Thomas; Van Damme, Petra; Martinho, Rui Gonçalo; Helsens, Kenny; Hole, Kristine; Pimenta-Marques, Ana, et al. (2011). NatF Contributes To An Evolutionary Shift In Protein N-Terminal Acetylation And Is Important For Normal Chromosome Segregation PLOS Genetics 7, 7.
A polyphenolic compound produced in plants in response to injury or pathogenic attack from bacteria or fungi. Resveratrol exerts a diverse array of biological effects, including antitumor, antioxidant, antiviral, and hormonal activities. It activates sirtuin 1 (SIRT1), an enzyme that deacetylates proteins and contributes to cellular regulation (including autophagy). Dietary sources of resveratrol include grapes, blueberries, raspberries, and mulberries.
Resveratrol Autophagy ↑ Deacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy
A polyamine (an organic compound having more than two amino groups) named for having been isolated in semen. Spermidine has since been found in a variety of different tissue types, as well as foods. It is best known for its role as a potential autophagy and longevity promoter with its effects having been demonstrated in yeast, flies, worms, and human immune cells.[1]
↓ Acetyltransferase activity (especially EP300) → ↓ cytosolic Acetyl CoA → Autophagy
↓ mitochondrial transmembrane potential → ↑ ubiquitination → mitophagy (preferentially targeted)
- ^ Hartl, Regina; Megalou, Evgenia; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix, et al. (2009). Induction Of Autophagy By Spermidine Promotes Longevity Nature 11, 11.
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