A key regulator of the process of autophagy is a drop in cellular levels of acetyl CoA, an end product of nutrient metabolism. As one would expect, fasting – the abstention from all nutrients – is a potent inducer of autophagy. This is especially true in mice, which begin to experience autophagy within a few days of fasting. However, critical metabolic differences between mice and humans make it difficult to extrapolate these findings to humans. In this clip, Dr. Guido Kroemer describes the current state of knowledge about the minimum amount of time required for fasting-induced autophagy in humans.
-Rhonda: So it kind of brings up another question I had which related to when you started talking about how you can fast, and fasting in organisms like rodents and also in some human volunteers does induce autophagy. And the question that I had for you is, like, I've talked with Dr. Valter Longo, he was on the podcast, and he talked quite a bit about his research on prolonged fasting in both rodents and also in humans and how the prolonged fast, at least, in rodents is 48 hours, which in humans is around 4 days, 4 to 5 days. And that was able to very robustly, not only activate autophagy, but also cell death, and that was followed by a regeneration period. But, the question is do we know what the minimum amount of fasting time is for humans or rodents that can activate autophagy? So for example, when I'm not pregnant, I usually followed a very time-restricted eating schedule where I like to eat all of my food within at least 10 hours, and then I fast for 14 hours every night. Some people do even more strict. They eat within 8 hours and they fast for 16 hours. Does that 16-hour fast induce any autophagy in any of our tissues? Is there any evidence, do we know?
Dr. Kroemer: We don't know. So, Craig Thompson published a paper on circadian variations in hepatic autophagy. So you know that mice don't eat during the day and they eat during the night, and so, the entire cycle is inversed. And he observed that as a result of not eating during the day, there was more autophagy in the liver. So this result is intriguing. It has not been, to my knowledge, extrapolated to other organs. And it still certainly requires more profound studies.
Rhonda: Okay. When you say during...
Dr. Kroemer: So what we did on circulating leukocytes is that we needed to wait for three or four days to see a massive induction of autophagy. There's a fundamental difference between rodents and humans, and so, the two days that you have been alluding to cause a 20% weight loss in mice, that are, at this time point, at the verge of death. Another day would potentially kill them. And so, 20% is a lot, so imagine this for yourself.
Rhonda: In two days.
Dr. Kroemer: In four days, a human being only loses one to two percent of his or her weight.
Rhonda: Is that because they have a higher metabolism, rodents do, or...?
Dr. Kroemer: Yeah, it's certainly linked to the change in the surface volume ratio that is classically associated with an accelerated metabolism.
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