IGF-1 plays a major role in the proliferation of stem cells during the refeeding phase | Valter Longo
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Insulin-like growth factor-1, or IGF-1, plays a primary role in the refeeding phase that occurs after fasting, which is essential for the generation of healthy cells. During fasting, when IGF-1 is low, damaged cells die and stem cells are activated. However, during refeeding, IGF-1 levels rise and stem cells proliferate and continue to grow. Eating sufficient protein during refeeding is necessary to provide the essential amino acids for cell growth and also to stimulate the growth factor IGF-1, which provides the signals to rebuild. In this clip, Dr. Valter Longo describes the pivotal role that IGF-1 plays in the proliferation of stem cells and the importance of consuming sufficient protein.
Rhonda: I recall in our last discussion you mentioned the refeeding phase was really important for the stem cell proliferation, so after you activate them, you want them to proliferate and continue to grow. And you had mentioned, if I remember correctly, that IGF-1 played a major role in that proliferation because it is after all a growth signal, you know?
Valter: Yes, so there's no doubt. We haven't spent too much time on it but it's pretty obvious that, you know, you'll need growth factors to do that.
So, this also makes us think about for example the clinical trial, the multiple clinical trials that were done on IGF-1, in cancer, that failed, right? And we thought, well maybe they failed because the IGF-1 was also needed for example for the immune system to be built or rebuilt, and, in those trials, right? So then the generation of healthy cells is as important as the low IGF-1...generation of healthy cells is IGF-1-dependent, is probably as important as the killing of damaged cells that is low IGF-1-dependent, and the turning on of stem cells, which is also low IGF-1-dependent. So...
Rhonda: Oh, it's low? I thought it was higher, the...turning on the stem cell...not turning on, the proliferation of them is high IGF-1, correct?
Valter: Yeah, no, but the turning on, the initial one is low. So low now is the signal to self-renew, you know?
Rhonda: Yeah.
Valter: So now you have a population, a small population of stem cells that are just active and standing by. Then probably when IGF-1 goes back up, now they are the ones that are pushed by IGF-1 to proliferate and to differentiate, probably also to differentiate. Proliferate and differentiate. Because now you want to rapidly make...
Rhonda: Make new cells.
Valter: ...a lot of white blood cell for example or whatever it is.
Rhonda: So that's my question about, my question to you then is for the refeeding phase then, you may...is that...do you think then for example having some protein would be a little more important because you want...protein being essential amino acids...because you want a little more IGF-1 activated during that specific time window? Is that something that you...
Valter: Yeah, there is no doubt that when you refeed, you have to have sufficient protein to rebuild. And if you don't, I mean, you really don't have the bricks to rebuild whatever system you partially broke down. So yeah, protein...and also protein are going to drive the IGF-1. So the whole system of course is set up to...the sugar and the protein is set up to give the signals to rebuild, which is probably through IGF-1. Insulin and IGF-1.
The biological process in which a cell matures and specializes. Differentiation is essential for the development, growth, reproduction, and lifespan of multicellular organisms. Differentiated cells can only express genes that characterize a certain type of cell, such as a liver cell, for example.
Amino acids that cannot be synthesized by the organism, but must be supplied via diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine.
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 naturally occurring substance capable of stimulating cellular growth, proliferation, healing, and differentiation. Growth factors typically act as signaling molecules between cells. Examples include cytokines and hormones that bind to specific receptors on the surface of their target cells.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
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.
A cell that has the potential to develop into different types of cells in the body. Stem cells are undifferentiated, so they cannot do specific functions in the body. Instead, they have the potential to become specialized cells, such as muscle cells, blood cells, and brain cells. As such, they serve as a repair system for the body. Stem cells can divide and renew themselves over a long time. In 2006, scientists reverted somatic cells into stem cells by introducing Oct4, Sox2, Klf4, and cMyc (OSKM), known as Yamanaka factors.[1]
- ^ Takahashi, Kazutoshi; Yamanaka, Shinya (2006). Induction Of Pluripotent Stem Cells From Mouse Embryonic And Adult Fibroblast Cultures By Defined Factors Cell 126, 4.
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