Growth hormone defect protects against cancer, diabetes, & cognitive decline | Valter Longo
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Insulin-like growth factor-1, or IGF-1, is a hormone that plays key roles in growth and is the key mediator of growth hormone activity. It is produced primarily in the liver, and its synthesis and release are promoted by dietary intake of protein, especially those containing the amino acids methionine and cysteine. Emerging evidence suggests that IGF-1 also regulates the aging process via its influence on growth hormone. In this clip, Dr. Valter Longo describes the IGF-1 pathway and explains how defects in the pathway influence disease risk.
Rhonda: But for people that are listening and kind of wondering, we're talking about one of the major dietary regulators of the IGF-1 pathway which maybe you can mention a little bit about the role of IGF-1 in the aging process.
Valter: Yeah. So, proteins, and particularly certain amino acids, methionine, cysteine, etc., they regulate IGF-1 levels, and IGF-1 in simple organisms, at least the orthologs of IGF-1, as well as in mammals seem to have an important role in aging. It is not clear how much is IGF-1 versus insulin versus growth hormone receptor-dependent signaling, which is independent of IGF-1 and insulin, but most likely it is the growth hormone receptor. Growth hormone and growth hormone receptor, they are the sort of master controllers, and IGF-1 seems to be one of the axis that regulates or accelerates aging in multiple cell types.
Rhonda: And from humans there are some, there's some evidence with polymorphisms and various like growth hormone...?
Valter: Yeah, that's actually our work with not polymorphism but mutations in the growth hormone receptor, something called E180 mutation. And the people...Well, we knew from mice, from the work of John Kopchick and Andrzej Bartke, that mice that have either a growth hormone receptor, or growth hormone deficiency, live longer, about 40% longer, they also live much healthier. That's probably, you know, I think one of the most important observations made in the aging field, that you could live 40% longer, and yet about half of the mice get to the end of life without any obvious pathological lesions, so they don't develop diseases. And that the control of disease is less than 10%.
So, and these...
Rhonda: It's pretty significant.
Valter: I'm pointing these out...Well, it's a huge effect right there. I'm pointing these out because obviously people think that if we extend the lifespan of, human lifespan, then it's going to come with a lot of more problems. And instead, in the mice, but also in our work in humans, where we've been following these people with growth hormone receptor deficiency down in Ecuador, and they're called, there's a syndrome there, a syndrome called Laron's syndrome.
So they're very much the equivalent to the mice, and they don't have a very long lifespan, they may live a few years more than their relatives, they don't have homozygous growth hormone receptor deficiency, but they're protected from cancer, they're protected from diabetes, and a recent paper showed that they seem to be protected from age-dependent cognitive decline, and all of these are matched by the mouse work.
A bidirectional cell signaling pathway that may regulate cell function, metabolism, or other aspects of physiology. Most signaling pathways are unidirectional. However, an axis may involve two or more signaling proteins and their secreting organs or cells in a type of feedback loop. For example, the growth hormone/IGF axis, also known as the Hypothalamic–pituitary–somatotropic axis, is a highly regulated pathway involving IGF-1 (produced by the liver), growth hormone (produced by the pituitary), and growth hormone-releasing hormone (produced by the hypothalamus).
A type of growth hormone receptor mutation commonly found among people of Spanish and Jewish descent that results in Laron syndrome, a genetic disorder characterized by unusually short stature. Scientific evidence suggests that people with Laron syndrome have lower risk of developing cancer or type 2 diabetes.
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 sulfur-containing amino acid that is a constituent of most proteins. It is an essential nutrient in the diet of vertebrates. Methionine restriction in lower organisms has been shown to extend lifespan.
A gene in two or more species that has evolved from a common ancestor during a speciation event. Orthologous genes encode proteins with the same function in different species.
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