IGF-1
Es la hormona IGF-1 buena o mala? (Y la ingesta de carne que la eleva…)
IGF-1 is one of our body’s most important anabolic hormones. Anabolic hormones are in charge of growth, and growth can be both good or bad depending on context.
Animal protein raises IGF-1 more than other foods, but this doesn’t mean meat is bad for you, or is “as bad as smoking cigarettes” as some headlines have proclaimed.
When IGF-1 levels are too high, some forms of cancer grow more easily (mainly prostate and breast). However, when IGF-1 levels are low, risks of cardiovascular disease, dementia, Alzheimer’s, and sarcopenia are all much higher. In fact, death to cancer is also much more common with low IGF-1 too, possibly due to increased risk of cachexia (muscle wasting).
While diseases associated with high IGF-1 levels are scary, the truth is that low IGF-1 levels are more likely to be of concern for many people. If you are worried about IGF-1 levels, perhaps the best action you can take is to exercise frequently. Frequent exercise cuts the risk of cancers associated with IGF-1 to a much greater extent than cutting animal protein does, and also doesn’t predispose you to the diseases associated with low IGF-1. In fact, the risk of all of the diseases associated with low IGF-1 are also reduced when you exercise frequently.
Dairy products contain high levels of dioxins, which are proven potent carcinogens.
IGF-1 stands for “insulin-like growth factor 1”, and as the name implies, it performs a similar sort of job as insulin. Most people know that insulin is related to blood glucose, and maybe that insulin helps the body move that glucose into different organs (such as the muscles or the fat).
We usually think of insulin being released in relation to a high-carbohydrate meal, but in reality both carbohydrates and protein are well-capable of raising insulin. IGF-1 release is more complicated, with multiple interactions with other hormones such as growth hormone, but ultimately it appears to be correlated with animal protein intake (particularly dairy) and also fat intake. Since carbohydrates can increase insulin, and insulin can affect IGF-1, there is some correlation with carbohydrates, but overall it doesn’t appear to be as strong as the correlation between animal protein and fats.
Both the muscle-building process and the fat-storage process are anabolic reactions, but one is generally considered to be positive and the other negative. On the far end of the spectrum, a cancer cell grows via anabolic reactions.
Ultimately, we can’t say that insulin is definitely good or definitely bad; we can only say that depending on the context, it may promote health or harm. Optimally, you want to do everything you can to encourage insulin’s healthy effects, not its harmful effects, but sometimes it’s not such an easy distinction to make!
Molecularly, IGF-1 is very similar to insulin, and is similarly anabolic. IGF-1 helps children develop physically into adults, and it continues to help adult cells to grow and divide. Without healthy levels of IGF-1, children fail to develop properly, resulting in dwarfism, and adults lose muscle mass and suffer from overall weakened strength.
The main point here is that context is highly important when it comes to discussing IGF-1—it’s not as simple as saying that IGF-1 is good or that it’s bad. When IGF-1 is helping the muscles adapt to exercise, it’s good, whereas when IGF-1 is helping cancer cells to divide and develop a blood supply (angiogenesis), it’s bad. This context is why it’s so important to consider lifestyle along with diet when approaching IGF-1, and why we need to take some of the sensationalistic headlines with a grain of salt.
A meta-analysis of studies examining the correlation between high IGF-1 levels and different cancers only found increased risk of prostate and pre-menopausal breast cancers, suggesting that perhaps it’s premature to say that high levels of IGF-1 would predispose someone to cancer. There are many more cancers, and many more deadly cancers, that did not appear to be highly correlated.
A second meta-analysis observed that men with low IGF-1 levels actually had significantly higher risk of death due to cancer than men with normal (not high) levels. In this case, no studies involving cancer risk and IGF-1 in women were included, so we cannot assume the same will be true in women–though we might expect it to be similar given our knowledge of how IGF-1 affects the human body.
Cancer is associated with both high levels of IGF-1 and low levels!
Cachexia is a condition associated with IGF-1 deficiency, and is thought to be responsible for upwards of 30% of all cancer deaths (as opposed to the cancer itself). Around 50% of patients with cancer die in a state of cachexia. Overall, preventing cachexia is an important part of treating cancer, and this means that IGF-1 needs to be kept at an optimal level—not too high, not too low. Therefore, attempting to cut IGF-1 drastically is not a recommended strategy, and could very likely cause more problems!
Another link which frequently makes headlines is that eating animal protein is correlated with cancer. In reality, apart from processed meat, we can’t actually make a strong link.
Cancer is a scary disease, but cardiovascular diseases (CVD) consistently outrank all cancers combined as the leading cause of death in the United States. When examining the relationship between IGF-1 levels and CVD, we actually witness an inverse relationship, meaning that risk of CVD increases as IGF-1 decreases.
In humans, we’ve witnessed that IGF-1 is directly beneficial on a number of factors involved in CVD risk. IGF-1 reduces oxidative stress on the blood vessels, reduces the number of blood vessel cells that die, reduces inflammation, and improves the stability of plaques already formed, making them less likely to cause dangerous clots that can cause problems like strokes. In this way, keeping IGF-1 levels normal protects against CVD and CVD mortality.
Increased IGF-1 levels appear to improve cognitive function in the elderly. It’s possible that declining IGF-1 levels play a significant role in the loss of mental function frequently associated with aging!
Men with low levels of IGF-1 had a 45% increased risk of hip fracture for every decline of roughly 50 ng/mL. At around 150 ng/mL, the association becomes insignificant, indicating that IGF-1 levels above this level are unlikely to be protective.
Higher IGF-1 levels also predicted a lower loss of lean muscle mass in aging men. Sarcopenia, a condition where the muscles begin to waste away, becomes more and more common as you grow older, in part due to declining IGF-1 levels.
Men in the bottom 10% of IGF-1 levels have an overall 38% greater risk of death (though by the 20th percentile, the association disappears).
One study showed that the female offspring of centenarians had significantly higher levels of IGF-1, though they also had reduced IGF-1R levels (a receptor that IGF-1 binds to in order to cause an effect). The researchers hypothesized that the higher IGF-1 levels may have been the body’s way of compensating for reduced receptor activity, but the result is the same: IGF-1 was higher, not lower, in the female offspring of individuals who lived to be at least 100 years old.
Exercising frequently is much more important for cutting cancer risk than cutting meat intake.
Former female collegiate athletes had only 16%the risk of pre-menopausal breast cancer compared to non-athletes.
Que te ocurre si careces completamente de IGF-1?
Ecuadorean Villagers May Hold Secret to Longevity
Published: February 16, 2011People living in remote villages in Ecuador have a mutation that some biologists say may throw light on human longevity and ways to increase it.
The villagers are very small, generally less than three and a half feet tall, and have a rare condition known as Laron syndrome or Laron-type dwarfism.
They are also almost completely free of two age-related diseases, cancer and diabetes.
As Dr. Guevara-Aguirre accumulated health data on his patients, he noticed a remarkable pattern: though cancer was frequent among people who did not have the Laron mutation, those who did have it almost never got cancer. And they never developed diabetes, even though many were obese, which often brings on the condition.
“I discovered the population in 1987,” Dr. Guevara-Aguirre said in an interview from Ecuador. “In 1994, I noticed these patients were not having cancer, compared with their relatives. People told me they are too few people to make any assumption. People said, ‘You have to wait 10 years,’ so I waited. No one believed me until I got to Valter Longo in 2005.”
The Laron patients have a mutation in the gene that makes the receptor for growth hormone. The receptor is a protein embedded in the membrane of cells. Its outside region is recognized by growth hormone circulating through the body; the inside region sends signals through the cell when growth hormone triggers the receptor.
The Laron patients’ mutation means that their growth hormone receptor lacks the last eight units of its exterior region, so it cannot react to growth hormone. In normal children, growth hormone makes the cells of the liver churn out another hormone, called insulinlike growth factor, or IGF-1, and this hormone makes the children grow. If the Laron patients are given doses of IGF-1 before puberty, they can grow to fairly normal height.
This is where the physiology of the Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal.
The Laron patients have the equivalent defect — their cells make very little IGF-1, so very little IGF-1 signaling takes place, just as in the DAF-2-ablated worms. So the Laron patients might be expected to live much longer.
Because of their striking freedom from cancer and diabetes, they probably could live much longer if they did not have a much higher than usual death rate from causes unrelated to age, like alcoholism and accidents.
Dr. Longo said he believed that having very low levels of IGF-1 was the critical feature of the Laron patients’ freedom from age-related diseases.
First, the serum protected the cells from genetic damage. Second, it spurred the cells that were damaged to destroy themselves, a mechanism the body uses to prevent damaged cells from becoming cancerous. Both these effects were reversed when small amounts of IGF-1 were added to the serum.
Dr. Longo said that some level of IGF-1 was necessary to protect against heart disease, but that lowering the level might be beneficial. A drug that does this is already on the market for treatment of acromegaly, a thickening of the bones caused by excessive growth hormone. “Our underlying hypothesis is that this drug would prolong life span,” Dr. Longo said. He said he was not taking the drug, called pegvisomant or Somavert, which is very hard to obtain.
A strain of mice bred by John Kopchick of Ohio University has a defect in the growth hormone receptor gene, just as do the Laron patients, and lives 40 percent longer than usual.
Dr. Harry Ostrer, a geneticist at New York University who is exploring the Laron patients’ degree of Sephardic ancestry, said that he had seen several of Dr. Guevara-Aguirre’s patients in Quito, Ecuador’s capital, and that they were “remarkably youthful in appearance.”
The hormone IGF-1 comes up a lot in your research; it seems to be a big factor in mediating the effects of calorie restriction and fasting. How big of a role do you think IGF-1 is playing overall in aging?
I think it’s a pretty big role, though it’s not the only thing that’s important. The reduction of IGF-1 is really key in the anti-aging effects of some of the interventions. Both the dietary ones and the genetic ones. We’ve been putting a lot of work into mutations of the growth hormone receptor that are well established now to release IGF-1 and also cause a record life span extension in mice. So we know for example with chemotherapy resistance if you fast mice and inject IGF-1 you reverse a lot of the protective effects of fasting. So it’s important; it’s not the only factor, but it’s certainly one of the key ones.
So could we expect drugs targeting IGF-1 to work in humans?
We’re working on that both with the diet but also with drugs. So we’ve been working on that for a while and we’re getting closer to it. Of course the pharmacological part is much more complicated and expensive and so eventually we need to have big pharma partnered to do it – and that may occur very soon. But yes the growth hormone receptor/IGF-1 pathway is going to be our first target. And in fact we just organised a conference about a year ago on this, on an intervention to extend the human health span in targeting the growth hormone/IGF-1 pathway. We brought 30 of the leading experts in the world on this to Sicily and at the end everybody voted and the growth hormone IGF-1 came out most likely to be active in extending human lifespan.
So is that the direction your research will be heading in over the next few years?
Yes. And of course we are even more interested in regeneration and rejuvenation now. We just published a paper on that, showing how fasting and IGF-1 can cause stem cell based regeneration and rejuvenation of the immune system. So half of my lab has now switched to understanding how this can regenerate systems – and not just regenerate in an unsophisticated way, but regenerate in a very sophisticated way which is reminiscent of what you see during early development.
Fuente: http://michelsonmedical.org/2014/12/26/ … ter-longo/