This episode will make a great companion for a long drive.
A blueprint for choosing the right fish oil supplement — filled with specific recommendations, guidelines for interpreting testing data, and dosage protocols.
The fasting-mimicking diet holds great promise as a complementary therapy for cancer because, when coupled with chemotherapy, the diet induces differential stress resistance – a phenomenon in which normal cells are protected from stress, but damaged cells are not. Fasting creates a hostile microenvironment for cancer cells, sensitizing them to chemotherapy drugs and promoting cell death. This exploits the inability of cancer cells to adapt to extreme environments. In this clip, Dr. Valter Longo describes the origins of the fasting-mimicking diet and explains how it enhances chemotherapeutic treatments.
Rhonda: ...but the fasting, you've done a lot of work on both, doing periodic fasting, water fasting, and also a fasting-mimicking diet which you can explain in a minute.
So I was kind of...I found it kind of interesting, like the reason why you developed the fasting-mimicking diet, at least I read in your recent book, "The Longevity Diet," was if I'm correct, because you were doing some studies on cancer patients. And, is that correct, the...
Valter: Yes. So we...Well, first of all for a long time I had been thinking about how to get the benefits of calorie restriction without the problems of calorie restriction, and so that was something that I was looking for. And also I, you know, back in the days in my graduate work, you know, we were starving yeast and bacteria, and we had shown that this was very beneficial. So I was really...I wanted to look at the possibility that prolonged fasting will be beneficial.
And so...then also the point when we discovered that the proto-oncogenes, so the normal versions of the oncogenes that are so central in cancer, they are the genes that control cellular protection. And so from that came the idea that...and maybe we discussed that already in the first interview. But that came the idea that if you starve a system, the normal cells would become protected, and the cancer cells will remain sensitive, so then we started testing this in cancer patients, but realized that they didn't want to fast.
And then I think they gave us an opportunity and the motivation to look for a fasting-mimicking diet, so a diet that works as well as fasting, but allows patients to eat. And this was funded by the National Cancer Institute first, and then by the National Institute on Aging.
And so it's of course exploring all these understanding, all the understanding of the connection between let's say amino acids and TOR and IGF-1, sugars or certain sugars, and PKA actually we'd shown that, as we had shown for yeast, we now shown in mammalian cells that glucose levels activate PKA, and so that's part of the...that's a lot of what went into the development of a diet that can nourish the patient and yet have effects on IGF-1, IGFBP-1, ketone bodies, and glucose that is equivalent to that of water-only fasting.
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.
Also known as insulin-like growth factor-binding protein 3. One of the six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity, preventing them from binding to the IGF-1 receptor (IGF1R). IGFBP-3 exerts antiproliferative effects in many cell types.
One of the most potent natural activators of the AKT signaling pathway. IGF-1 stimulates cell growth and proliferation, inhibits programmed cell death, mediates the effects of growth hormone, and may contribute to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role in growth during childhood and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
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.
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
A gene that has the potential to cause cancer. A proto-oncogene is a normal gene that regulates cell growth and proliferation but if it acquires a mutation that keeps it active all the time it can become an oncogene that allows cancer cells to survive when they otherwise would have died.
A type of intermittent fasting that exceeds 48 hours. During prolonged periods of fasting, liver glycogen stores are fully depleted. To fuel the brain, the body relies on gluconeogenesis – a metabolic process that produces glucose from ketones, glycerol, and amino acids – to generate approximately 80 grams per day of glucose [1]. Depending on body weight and composition, humans can survive 30 or more days without any food. Prolonged fasting is commonly used in the clinical setting.
[1] Longo, Valter D., and Mark P. Mattson. "Fasting: molecular mechanisms and clinical applications." Cell metabolism 19.2 (2014): 181-192.
A family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). Protein kinase A has several functions in the cell which vary with cell type, including regulation of glycogen, sugar, and lipid metabolism. Kinases, in general, modify the activity of other proteins by chemically adding phosphate groups to them in a process known as phosphorylation.
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