18 replies to this topic

[solbanger]

They mostly die of accidents or heart disease or strokes. Out of 100 of them only one has had cancer on her ovaries. Interesting study.

http://www.cnn.com/2...rss_igoogle_cnn

[ggranger007]

There is more on it at ScienceDaily: http://www.scienceda...gle Feedfetcher

Interesting study. This doesn't bode well for my 6'3" stature! Coincidentally enough, my 6'3" grandfather had diabetes and died of cancer.

[xEva]

NY Times covered it best Ecuadorean Villagers May Hold Secret to Longevity

By NICHOLAS WADE

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.

...

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. In collaboration with Dr. Guevara-Aguirre, he exposed human cells growing in a laboratory dish to serum from the Laron patients. The cells were then damaged with a chemical that disrupts their DNA. The Laron serum had two significant effects, the two physicians reported on Wednesday in Science Translational Medicine.

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.

[mikeinnaples]

I read this last night as am curious if this is going to ultimately lead to therpies to reduce IGF after reaching maturity for broad spectrum preventative medicine. Guess time will tell.

[maxwatt]

Lycopene?

Eur J Cancer Prev. 2007 Aug;16(4):298-303.
Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients.
Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy J.

Colorectal Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, Beer-Sheva, Israel.
Abstract
Epidemiological studies have shown that high serum levels of insulin-like growth factor-I are associated with an increased risk of colon and other types of cancer. The aim of this study was to determine whether short intervention with dietary tomato lycopene extract will affect serum levels of the insulin-like growth factor system components in colon cancer patients. The study had a double-blind, randomized, placebo-controlled design. Colon cancer patients (n=56), candidates for colectomy, were recruited from the local community a few days to a few weeks before surgery. Personal and medical data were recorded. Plasma concentrations of insulin-like growth factor-I and II and insulin-like growth factor-I-binding protein-3 were assayed by routine laboratory methods. Lycopene was assayed by high-performance liquid chromatography. Plasma lycopene levels increased by twofold after supplementation with tomato lycopene extract. In the placebo-treated group, there was a small nonsignificant increase in lycopene plasma levels. The plasma concentration of insulin-like growth factor-I decreased significantly by about 25% after tomato lycopene extract supplementation as compared with the placebo-treated group (P<0.05). No significant change was observed in insulin-like growth factor-I-binding protein-3 or insulin-like growth factor-II, whereas the insulin-like growth factor-I/insulin-like growth factor-I-binding protein-3 molar ratio decreased significantly (P<0.05). Given that high plasma levels of insulin-like growth factor-I have been suggested as a risk factor for various types of cancer including colon cancer, the results support our suggestion that tomato lycopene extract has a role in the prevention of colon and possibly other types of cancer.

PMID: 17554202

Eur J Clin Nutr. 2007 Oct;61(10):1196-200. Epub 2007 Feb 7.
Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial.
Graydon R, Gilchrist SE, Young IS, Obermüller-Jevic U, Hasselwander O, Woodside JV.

Nutrition and Metabolism Group, Centre for Clinical and Population Science, Queen's University Belfast, Northern Ireland, Belfast, UK.
Abstract
OBJECTIVE: Studies have suggested a link between lycopene and insulin-like growth factor-1 (IGF-1). The aim of this study was to test the effect of lycopene supplementation on IGF-1 and binding protein-3 (IGFBP-3) status in healthy male volunteers. DESIGN, SETTING, SUBJECTS AND INTERVENTION: This was a 4 week randomized, double-blind, placebo-controlled study of lycopene supplementation (15 mg/day) in healthy male volunteers (n=20). Fasting blood samples were collected at baseline and after 4 weeks. Samples were analysed for lycopene by high-performance liquid chromatography (HPLC) and IGF-1 and IGFBP-3 by enzyme-linked immunosorbent assay (ELISA). Changes in end points from baseline were compared in those who received placebo versus those who received the lycopene supplement.

RESULTS: Median change in lycopene from baseline (post-supplement - baseline) was higher in subjects in the intervention than those on placebo (lycopene group 0.29 (0.09, 0.46); placebo group 0.03 (-0.11, 0.08) micromol/l; median (25th, 75th percentiles), P<0.01). There was no difference in median change in IGF-1 concentrations (lycopene group -0.6 (-2.6, 1.9); placebo group -1.15 (-2.88, 0.95) nmol/l, P=0.52), or median change in IGFBP-3 concentrations (lycopene group 245 (-109, 484); placebo group 101 (-34, 234) nmol/l, P=0.55) between intervention and control groups. Change in lycopene concentration was associated with the change in IGFBP-3 in the intervention group (r=0.78; P=0.008; n=10).

CONCLUSIONS: Lycopene supplementation in healthy male subjects has no effect on IGF-1 or IGFBP-3 concentrations in a healthy male population. However, the association between change in lycopene concentration and change in IGFBP-3 in the intervention group suggests a potential effect of lycopene supplementation on IGFBP-3.

PMID: 17299493

[VidX]

Interesting - yes, applicable? - probably no... I doubt anyone would like to experience early sarcopenia + bone loss, overall - this is just another "Trade off" scenario, where you chose one - loose another.. We won't reach much in this way IMHO, time to repair, reprogram, replace or whatever else action to "reverse" aging, not to slow it by means of trade-offs. (Mice living "almost" two times longer? pff.. Look at that p53 knockout mice then.. Methusellah flies are more active, more fertile, more capable/etc and still live 5-6times longer, that's a good "tinkering" of genome. Sadly - not by the means applicable to us)..
Oh, and these dwarf doesn't look young at all. Andy Milonakis - that's a dwarf that looks young, not these..

Edited by VidX, 17 February 2011 - 11:04 PM.

[capsun]

Flax lignans are potent inhibitors of IGF-1 as well.

[resveratrol_guy]

Bump! I think this needs to be revisited in a post-CRISPR world. It ain't 2011 anymore, and we might be able to shut down the majority of IGF1 production using gene therapy, thereby inducing Laron syndrome with its small but nonzero IGF1 production. Even VidX's fears of 4 years ago are now on the precipice of being moot, as myostatin therapy appears poised to cure sarcopenia. So, in other words, wait until full muscle development, then as soon as you've had your final child, shut down IGF1 and myostatin at the same time, presumably leaving you with good musculature but virtually no capacity to fuel uncontrolled tissue growth. Although we could presumably shut down IGF1 via a variety of genes, it would be most prudent to start by inducing the exact Laron mutation involving GHR. The quick-and-dirty option might be to take pegvisomant, but I know nothing about it apart from what was mentioned in the NY Times article.

 

99% reduction in cancer blows away anything we have at the moment. And look at the photos of those Ecuadorians with this disease. They're hardly the picture of health. Imagine if they actually tried to eat right, exercise, etc. It may very well have a similar effect on dementia rates, although data is thus far lacking (in part, because none of them were reported as having it!).

 

So these folks have "squared the curve" better than any of us. They live a full life, then die quick. I don't think we can argue with that tradeoff.

 

Edited by resveratrol_guy, 05 December 2015 - 01:42 AM.

[corb]

So these folks have "squared the curve" better than any of us. They live a full life, then die quick. I don't think we can argue with that tradeoff.

 

Well generally It'd be better if we can find something with no trade offs. Granted the trade offs of this sound like the people just died of the next most probable cause of mortality and ones that should be treatable in the future so maybe it's not that bad. But :

 

 

"If we can establish that IGF1 is a risk factor for cancer, then you could imagine that doctors could prescribe IGF1-lowering drugs as we are now doing for cholesterol with statins,"

 

This could have the same end result statins had.
Sounds like a good idea on paper, but it's one of those things that you just can't know until you try.

 

Edited by corb, 06 December 2015 - 04:28 PM.

[resveratrol_guy]

We won't find something without tradeoffs. Biology doesn't work like that. I think pretty much anyone would rather die the way these folks do, by sudden accidents or cardiovascular events, than by dementia or cancer. What's more, Valter Longo's "minimouse" study suggests that they should live longer than the average bear if in fact they make an effort to lead a healthy lifestyle.

 

But I do agree that IGF1-lowering drugs are a dubious bet. I can well imagine a statin-like disaster playing out with them. That's why I think the safer route is IGF1 shutdown with gene therapy, whether via the Laron route, or some other compelling way.

 

[corb]

We won't find something without tradeoffs. Biology doesn't work like that.

 

For things like the metabolism and gene expression fine tuning , yeah, probably we won't find many treatments with no trade offs in the foreseable future, but I suspect there will be one or two, nature isn't perfect.

Researchers have made mice live longer than their maximum lifespan in labs quite easily without any observable trade offs so often as of late that reason likes to point out it's not even news anymore.

 

And we have to argue about  the semantics of a "trade off", there is a biological one if were still animals and survived by doing the hunter-gatherer meme, but these are people living in the modern world which albeit are suffering from a genetic condition which makes them less physically attractive, live longer and are more resistant to some diseases of old age, there is no clear trade off here - as far as longevity is concerned.

 

The danger I suspect will come from trying to get this effect in someone 3 times their size and body mass.

What effect will this have on the organs of someone who has a heart 2 times the one they have? Lungs almost thrice the size of their lungs, a much more substantial stomach ,etc.

The delivery mechanism isn't really all that important.

[resveratrol_guy]

 

We won't find something without tradeoffs. Biology doesn't work like that.

 

For things like the metabolism and gene expression fine tuning , yeah, probably we won't find many treatments with no trade offs in the foreseable future, but I suspect there will be one or two, nature isn't perfect.

Researchers have made mice live longer than their maximum lifespan in labs quite easily without any observable trade offs so often as of late that reason likes to point out it's not even news anymore.

 

And we have to argue about  the semantics of a "trade off", there is a biological one if were still animals and survived by doing the hunter-gatherer meme, but these are people living in the modern world which albeit are suffering from a genetic condition which makes them less physically attractive, live longer and are more resistant to some diseases of old age, there is no clear trade off here - as far as longevity is concerned.

 

The danger I suspect will come from trying to get this effect in someone 3 times their size and body mass.

What effect will this have on the organs of someone who has a heart 2 times the one they have? Lungs almost thrice the size of their lungs, a much more substantial stomach ,etc.

The delivery mechanism isn't really all that important.

 

 

Well, that's really the main open question here, which is what would happen if we artificially induced Laron syndrome after a human reached maximum size? Would it be a shock to the system to suddenly crash IGF1? I think, if it were, that a period of adjustment could be facilitated by gradually diminishing IGF1 supplelementation. Again, this is precisely the sort of question we ought to be trying to answer. The first test subjects, it seems to me, should be consenting individuals in terminal cancer, whose lives might be saved if it works. In any event, no other currently viable approach to halt cancer can compete with the sort of suppression offered by Laron syndrome, if the epidemiology is informative. That's worth more research.
 

[corb]

Well, that's really the main open question here, which is what would happen if we artificially induced Laron syndrome after a human reached maximum size? Would it be a shock to the system to suddenly crash IGF1? I think, if it were, that a period of adjustment could be facilitated by gradually diminishing IGF1 supplelementation. Again, this is precisely the sort of question we ought to be trying to answer. The first test subjects, it seems to me, should be consenting individuals in terminal cancer, whose lives might be saved if it works. In any event, no other currently viable approach to halt cancer can compete with the sort of suppression offered by Laron syndrome, if the epidemiology is informative. That's worth more research.

 

This is not an entirely unexplored subject, there are a number of studies like this one:

 

http://www.ncbi.nlm....les/PMC3845553/

 

However, many large clinical trials involving patients with adult tumors, including non–small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.

 

On the surface it looks like it's not a silver bullet.
Keep in mind the people suffering from Laron's are a small group and not every person gets cancer in their old age, so the cancer resistance observed might not be nearly as perfect as you think, it just looks like it is because the small number of people in the group.

At least when it does work, it works well.

[resveratrol_guy]

 

Well, that's really the main open question here, which is what would happen if we artificially induced Laron syndrome after a human reached maximum size? Would it be a shock to the system to suddenly crash IGF1? I think, if it were, that a period of adjustment could be facilitated by gradually diminishing IGF1 supplelementation. Again, this is precisely the sort of question we ought to be trying to answer. The first test subjects, it seems to me, should be consenting individuals in terminal cancer, whose lives might be saved if it works. In any event, no other currently viable approach to halt cancer can compete with the sort of suppression offered by Laron syndrome, if the epidemiology is informative. That's worth more research.

 

This is not an entirely unexplored subject, there are a number of studies like this one:

 

http://www.ncbi.nlm....les/PMC3845553/

 

However, many large clinical trials involving patients with adult tumors, including non–small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.

 

On the surface it looks like it's not a silver bullet.
Keep in mind the people suffering from Laron's are a small group and not every person gets cancer in their old age, so the cancer resistance observed might not be nearly as perfect as you think, it just looks like it is because the small number of people in the group.

At least when it does work, it works well.

 

 

Thanks for citing that metastudy. It may well be the most authoritative paper on IGF1 inhibitors to date. And you're right, the results are mixed. But what I'm proposing here is a preemptive strike on genetic expression before cancer sets in. I think that would be more successful, akin to eating a diet rich in polyphenols but stronger still, and would probably have fewer side effects than pharmaceuticals.

 

Your other point about the Laron's data sufferring from small sample size (and probably other genetic biases) is quite valid. I don't think IGF1 is a silver bullet. Nonetheless it seems likely to be the best thing we have.

[Rocket]

Seems like a lot here want to throw away the baby with the bathwater. The solution to cancer is NOT its all the fault of IGF1. Igf1 and hgh are wonderful chemicals for the body. From healing injuries, maintaining muscle mass, preventing skin from thinning, and even for rejuvenating the the thymus.

[resveratrol_guy]

Seems like a lot here want to throw away the baby with the bathwater. The solution to cancer is NOT its all the fault of IGF1. Igf1 and hgh are wonderful chemicals for the body. From healing injuries, maintaining muscle mass, preventing skin from thinning, and even for rejuvenating the the thymus.

 

Sure, there are other causes for cancer than IGF1, and other ways to stop it apart from shutting down IGF1. My only point is that it may well be the single most important target. The benefits you mention are important too, but the question is, where is the risk/reward balance? Without having a good way to measure one's proximity to cancer, it's a guessing game as to how far one can go.

 

Of relevance is this handy page on supercentenarians. Notice that Jean Calment was 4'11" and lived to 122. Sarah Knauss (Clark-Knauss) was 4'7" and lived to 117. Marie-Louise Meilleur was 4'11" and lived to 117. Edna Parker was 5'0" and lived to 114. In short, the champion ranks of longevity are dominated by short people. Yes, some skeletal shrinkage occurs with age, but even if we add a few inches to these figures, they still stand handily below average relative to their Caucasian female peers. While IGF1 isn't a silver bullet for longevity, I don't think this data is an accident, either.

[Rocket]

Seems like a lot here want to throw away the baby with the bathwater. The solution to cancer is NOT its all the fault of IGF1. Igf1 and hgh are wonderful chemicals for the body. From healing injuries, maintaining muscle mass, preventing skin from thinning, and even for rejuvenating the the thymus.

Sure, there are other causes for cancer than IGF1, and other ways to stop it apart from shutting down IGF1. My only point is that it may well be the single most important target. The benefits you mention are important too, but the question is, where is the risk/reward balance? Without having a good way to measure one's proximity to cancer, it's a guessing game as to how far one can go.

Of relevance is this handy page on supercentenarians. Notice that Jean Calment was 4'11" and lived to 122. Sarah Knauss (Clark-Knauss) was 4'7" and lived to 117. Marie-Louise Meilleur was 4'11" and lived to 117. Edna Parker was 5'0" and lived to 114. In short, the champion ranks of longevity are dominated by short people. Yes, some skeletal shrinkage occurs with age, but even if we add a few inches to these figures, they still stand handily below average relative to their Caucasian female peers. While IGF1 isn't a silver bullet for longevity, I don't think this data is an accident, either.

And plenty of other millions of short people die young or at an average age.

One important fact: when these supercentenarians were born, people on average were shorter than today. I'm not surprised people 120 years old in 2016 are shorter than people of today! The average height of a civil war soldier (male) was 5ft 8in. But yeah 4 11 is short by any ages standard.

Seems like a lot here want to throw away the baby with the bathwater. The solution to cancer is NOT its all the fault of IGF1. Igf1 and hgh are wonderful chemicals for the body. From healing injuries, maintaining muscle mass, preventing skin from thinning, and even for rejuvenating the the thymus.

Sure, there are other causes for cancer than IGF1, and other ways to stop it apart from shutting down IGF1. My only point is that it may well be the single most important target. The benefits you mention are important too, but the question is, where is the risk/reward balance? Without having a good way to measure one's proximity to cancer, it's a guessing game as to how far one can go.

Of relevance is this handy page on supercentenarians. Notice that Jean Calment was 4'11" and lived to 122. Sarah Knauss (Clark-Knauss) was 4'7" and lived to 117. Marie-Louise Meilleur was 4'11" and lived to 117. Edna Parker was 5'0" and lived to 114. In short, the champion ranks of longevity are dominated by short people. Yes, some skeletal shrinkage occurs with age, but even if we add a few inches to these figures, they still stand handily below average relative to their Caucasian female peers. While IGF1 isn't a silver bullet for longevity, I don't think this data is an accident, either.

And plenty of other millions of short people die young or at an average age.

One important fact: when these supercentenarians were born, people on average were shorter than today. I'm not surprised people 120 years old in 2016 are shorter than people of today! The average height of a civil war soldier (male) was 5ft 8in. But yeah 4 11 is short by any ages standard.

[resveratrol_guy]

And plenty of other millions of short people die young or at an average age.

One important fact: when these supercentenarians were born, people on average were shorter than today. I'm not surprised people 120 years old in 2016 are shorter than people of today! The average height of a civil war soldier (male) was 5ft 8in. But yeah 4 11 is short by any ages standard.

 

 

"But yeah 4 11 is short by any ages standard." -- That's really the point. It's not that shortness implies longevity. It's that it's almost required, apparently, as the majority of these old people were short relative to the background population, even in their birth year. There are surely ways to grow old while being tall or muscular, but they appear to be rare by comparison.

 

I still think turning down IGF1 activity by an order of magnitude after reproductive age is the way to go. It won't make you shorter, but in theory it could allow you to live a long life while forgetting about fasting. Have your cake and eat it too, maybe.
 

[Rocket]

 

And plenty of other millions of short people die young or at an average age.

One important fact: when these supercentenarians were born, people on average were shorter than today. I'm not surprised people 120 years old in 2016 are shorter than people of today! The average height of a civil war soldier (male) was 5ft 8in. But yeah 4 11 is short by any ages standard.

 

 

"But yeah 4 11 is short by any ages standard." -- That's really the point. It's not that shortness implies longevity. It's that it's almost required, apparently, as the majority of these old people were short relative to the background population, even in their birth year. There are surely ways to grow old while being tall or muscular, but they appear to be rare by comparison.

 

I still think turning down IGF1 activity by an order of magnitude after reproductive age is the way to go. It won't make you shorter, but in theory it could allow you to live a long life while forgetting about fasting. Have your cake and eat it too, maybe.
 

 

 

How does one explain that as HGH diminishes with age that cancer rates go up?  Put another way, when we're young and have high HGH cancer is low and as HGH production declines, cancer goes up?  I am not saying a direct cause and effect, but clearly the 2 are inversely proportional.  Have you looked at a graph of how drastic the reduction is HGH is after early adulthood?  With such a large fall off, naturally, what do you hope to gain by wiping out the very little that is left?