Periodic fasting has the same longevity benefit as caloric restriction | Guido Kroemer
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Calorie restriction, a promising strategy to extend lifespan, causes significant weight loss in mice. However, this dietary regimen is very difficult to adhere to. Interestingly, mice that are fed on an intermittent fasting schedule adjust to their restricted regimen and, in the end, tend to weigh as much as mice fed on a normal schedule, but they exhibit many of the physiological responses – including induction of autophagy – as calorie-restricted mice. In this clip, Dr. Guido Kroemer describes how intermittent fasting recapitulates the life-extension benefits of caloric restriction without some of the drawbacks.
- Dr. Kroemer: Actually, in mice, you can obtain exactly the same longevity extension that you would obtain, the 30% of caloric restriction by intermittent fasting. So, it's logistically much more difficult. Imagine, you have to weigh, for each mouse, the amount of food that they would eat normally, subtract 30%, put it in the cage, individual cages because calorically restricted mice tend to eat each other.
- Rhonda: Oh, wow.
- Dr. Kroemer: Yeah, they become aggressive because they are hungry.
- Rhonda: They become cannibals.
- Dr. Kroemer: Yeah, they become cannibals. So, it is logistically much more simple to take out the food from the cage completely, and to put back the food on the next day. So it's one day without any food, and another day with normal nutrition. And at the end, so, you have an oscillation of the weight of the mice, 10% every day. These oscillations tend to become smaller because the mice somehow adapt to this sort of stress, but the final result is that the intermittently fasted mouse has the same weight as a normally fed mouse. A difference with the calorically restricted mouse, it weighs also 20% to 30% less. And in spite of this difference in the body weight, intermittent fasting allows for a lifetime expansion in the same way as does caloric restriction. So, one can also consider that this may be more amusing to have, if I was a mouse, I would probably prefer the intermittent regimen, because it means satisfaction during one day and dissatisfaction on the other day, but not permanent dissatisfaction.
- Rhonda: Most people prefer doing intermittent fasting. I mean, it'll be very interesting to see more studies come out on, you know, the translation of this to humans and, as you mentioned, you needed three days of...was it a water fast they did? Was it a complete fast or they had coffee or...?
- Dr. Kroemer: Coffee. Tea.
- Rhonda: Okay. No food.
- Dr. Kroemer: No sugar, no milk. And water.
- Rhonda: Okay. So three days was enough to, at least, show signs of autophagy in circulating leukocytes. And Valter's work has shown, you know, four to five days and he's done. You know, he's got his fasting and then he's got the fasting-mimicking diet into... Some also hints that that also is enough. So, that's sort of encouraging. It would be more encouraging to have like a 24-hour fast or 48-hour. I mean, that's so much easier to do in general.
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.
The practice of long-term restriction of dietary intake, typically characterized by a 20 to 50 percent reduction in energy intake below habitual levels. Caloric restriction has been shown to extend lifespan and delay the onset of age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast.
A diet that mimics the effects of fasting on markers associated with the stress resistance induced by prolonged fasting, including low levels of glucose and IGF-1, and high levels of ketone bodies and IGFBP-1. More importantly, evidence suggests these changes in the cellular milieu are associated with a sensitization of cancer cells to chemotherapeutic drugs while simultaneously also conferring greater stress resistance to healthy cells.[1] Evidence also continues to emerge that properties of the fasting-mimicking diet, particularly its ability to cause immune cell turnover, may also make it useful in the amelioration of auto-immune diseases like multiple sclerosis.[2]
Fasting-Mimicking Diet Breakdown
- Day 1 - consists of 1,090 total calories (10% protein, 55% fat and 34% carbohydrate)
- Days 2 through 5 - consists of 725 total calories (9% protein, 44% fat and 47% carbohydrate)
[1] Cheng, Chia-Wei, et al. "Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression." Cell Stem Cell 14.6 (2014): 810-823. [2] Choi, In Young, et al. "A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms." Cell Reports 15.10 (2016): 2136-2146.
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 type of white blood cell. Leukocytes are involved in protecting the body against foreign substances, microbes, and infectious diseases. They are produced or stored in various locations throughout the body, including the thymus, spleen, lymph nodes, and bone marrow, and comprise approximately 1 percent of the total blood volume in a healthy adult. Leukocytes are distinguished from other blood cells by the fact that they retain their nuclei. A cycle of prolonged fasting has been shown in animal research to reduce the number of white blood cells by nearly one-third, a phenomenon that is then fully reversed after refeeding.[1]
- ^ Cheng CW; Adams GB; Perin L; Wei M; Zhou X; Lam BS, et al. (2014). Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell 14, 6.
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