Fasting associated with sickness behavior critical to surviving bacterial infection | Guido Kroemer
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A commonly observed behavior among mammals is the so-called "sickness behavior," where a person or animal that is sick will retreat, avoiding food and contact. This abstention from food induces autophagy and may serve as a means to modulate the body's inflammatory response. Artificially reversing this process in the laboratory – providing nutrients to sick animals – has proven fatal. In this clip, Dr. Guido Kroemer describes how fasting associated with sickness behavior is critical to surviving infection.
- Rhonda: Yeah. So, that's the question. Do we know the threshold for the stress threshold for, you know, activating autophagy, and when that pushes the mitochondria then to permeabilize and cause cell death? Like, where, for example, with Valter's work in mice, he had done 48-hour fasts and there was both autophagy and massive apoptosis occurring. So, is it just the intensity of the signal that can then say, "Okay, autophagy is not going to work here. We got to die." Or do we know?
- Dr. Kroemer: Well, autophagy in used in most cell types, while apoptosis is occurring in selected cell types. So what Valter has been observing, if I remember well, is destruction of leukocytes, right, white blood cells, which are very easily to be rebuilt. And so, the loss of 50% or 75% of leukocytes can be easily repaired in a few days. And it is a way to adapt the repertoire of immune cells to changing circumstances. It is a way also to inhibit unwarranted inflammatory reactions. So depending on the context, induction of autophagy can be actually a subtle way to avoid excessive inflammation. One example is the so-called sickness response. So, a cat or a dog or a human being or a mouse that is sick, that has a bacterial infection, will hide away, avoid light and noise, and will not eat. It's a classical phylogenetically conserved reaction in most cases of bacterial infection. And so this phenomenon leads to changes in the metabolism. Ketone in the production of ketone bodies, the reduction of glucose levels, presumably also induction of autophagy, and altogether these mechanisms avoid excessive inflammation that may be lethal. So Aslan Medzhitov published a paper in cell last year showing that force-feeding mice or just increasing the glucose levels to a normal concentration was sufficient to make bacterial infection that otherwise would have been able to cope with lethal.
- Rhonda: Wow. So, I know in humans too. And we have a bacterial infection, for example, a stomach virus or something that's bacterial of origin, you don't eat as well. So, it sounds like it's sort of a protective mechanism.
- Dr. Kroemer: It is.
- Rhonda: That's really interesting. I didn't know that.
Programmed cell death. Apoptosis is a type of cellular self-destruct mechanism that rids the body of damaged or aged cells. Unlike necrosis, a process in which cells that die as a result of acute injury swell and burst, spilling their contents over their neighbors and causing a potentially damaging inflammatory response, a cell that undergoes apoptosis dies in a neat and orderly fashion – shrinking and condensing, without damaging its neighbors. The process of apoptosis is often blocked or impaired in cancer cells. (May be pronounced “AY-pop-TOE-sis” OR “AP-oh-TOE-sis”.)
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 critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.
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.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
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