The question is, what if your IGF-1 is low from diet or lifestyle after growth phases (where I guess most of the side effects of dwarfism come from?).
I don’t believe U-shape (non-linear) associations that much, unless it’s obvious what’s causing the increase in mortality or whatever and what the confounding factors are.
Can you please elucidate, I don’t understand your question
I think any negative side effects from low IGF-1 in dwarfism might be the impact on growth in e.g childhood.
Does that make sense?
I’m tired so I operate at 5% capacity.
Ah Ah, no probs about the low battery level, I myself struggle to keep the charge up.
It may be, that the amazingly substantial beneficial side effects are only reaped when IGF-1 deficiency acts upon some mechanisms at growth.
Presently, I have no clear opinions on that. Longo does not suggest to seek low values of systemic IGF-1, he says the optimum is 140 ng/ml, the same cited in the article posted by Luke.
However, Longo implies that people over about 65 may refrain to eat more protein if they exercise with weights every day. he porbably alludes to the secretion of local IGF-1 in muscle and nervous tissue.
So far I couldn’t find much recent material, the studies on IGF-1 and cancer appear mostly to date back to early 2000 and previously.
This Lancet article is interesting, but they are cautious in determining a substatial cause-effect relationship.
ArticlesVolume 363, Issue 9418p1346-1353April 24, 2004
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Dr Andrew G Renehan, PhDa arenehan@picr.man.ac.uk ∙ Marcel Zwahlen, PhDc ∙ Prof Christoph Minder, PhDc ∙ Sarah T O’Dwyer, MDa ∙ Prof Stephen M Shalet, MDb ∙ Prof Matthias Egger, MDc,d
Affiliations & NotesArticle InfoLinked Articles (1)
Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk.
We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale.
We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1·49, 95% CI 1·14–1·95) and premenopausal breast cancer (1·65, 1·26–2·08) and high concentrations of IGFBP-3 were associated with increased risk of pre-menopausal breast cancer (1·51, 1·01–2·27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies.
Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.
I tried to question the Gemini AI and I must say the answer is pretty exhaustive and at least at first reading it appears overall reasonable. It also provides one or more link for every assertion it makes.
IGF-1 and cancer, is there any correlation or causation, the nature of such correlations causations, what the specialized medical literature says in updated studies
The relationship between IGF-1 (Insulin-like growth factor 1) and cancer is complex and has been the subject of extensive research. Here’s a breakdown of the current understanding based on specialized medical literature:
Correlation and Causation:
Nature of Correlations and Causations:
Key Points from Updated Studies:
It’s important to note that research in this area is ongoing, and a complete understanding of the complex interplay between IGF-1 and cancer is still evolving.
I posted this elsewhere but it also belongs here. Came out today
It is a complex issue, in fact, on the other side, it seems that low levels of IGF-1 may also be associated with higher cancer mortality, implying maybe that cancer can proliferate even with low concentrations of this specific growth factor. I can imagine a mechanistic cause like too low IGF-1 = excessive mTOR inhibition in the immune system = decreased immune response to cancer cells.
Both low and high serum IGF-I levels associate with cancer mortality in older men - PubMed.
J Clin Endocrinol Metab
. 2012 Dec;97(12):4623-30.
doi: 10.1210/jc.2012-2329. Epub 2012 Sep 26.
Johan Svensson 1, Daniel Carlzon, Max Petzold, Magnus K Karlsson, Östen Ljunggren, Asa Tivesten, Dan Mellström, Claes Ohlsson
Affiliations Expand
Background: Although recent population-based studies suggest a U-shaped relationship between serum IGF-I concentration and all-cause mortality, the distribution of death causes underlying this association remains unclear. We hypothesized that high IGF-I levels associate with increased cancer mortality, whereas low IGF-I levels associate with increased cardiovascular disease (CVD) mortality.
Methods: Serum IGF-I levels were measured in 2901 elderly men (mean age 75.4, range 69-81 yr) included in the prospective population-based Osteoporotic Fractures in Men Study (Sweden) study. Mortality data were obtained from central registers with no loss of follow-up. The statistical analyses included Cox proportional hazards regressions with or without a spline approach.
Results: During the follow-up (mean 6.0 yr), 586 of the participants died (cancer deaths, n = 211; CVD deaths, n = 214). As expected, our data revealed a U-shaped association between serum IGF-I levels and all-cause mortality. Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) associated with increased cancer mortality [hazard ratio (HR) = 1.86, 95% confidence interval (CI) = 1.34-2.58; and HR = 1.90, 95% CI = 1.37-2.65, respectively]. Only low serum IGF-I associated with increased CVD mortality (quintile 1 vs. quintiles 2-4, HR = 1.48, 95% CI = 1.08-2.04). These associations remained after adjustment for multiple covariates and exclusion of men who died during the first 2 yr of follow-up.
Conclusions: Our findings demonstrate that both low and high serum IGF-I levels are risk markers for increased cancer mortality in older men. Moreover, low IGF-I levels associate with increased CVD mortality.
The aging, anti-aging issues re IGF-1 I don’t have info or a view on.
What I do have a view and (from the stage at conferences) is that muscle mass is correlated with health and longevity and as we get older growing muscle gets harder and harder. So far is this true?
For me at 71yo male, carnivore at around 120gr protein/day intake (which IMHO is too low), Ipamorlan+Tesamorlan 3x mornings a week. Very light excersize on a vibration plate in front of decent LED power panels, 10# hand weights for just 10min a morning, then pushups till failure. Add in kaatsu.com C4 morning and night. I am growing good muscle on all 4 limbs. Composition improved to where I don;t want to loose any more weight or fat. Rapa for me helped loose weight slowly.
I’m happy with my arm and leg muscle building. Total weight drop is ok, but I’m below what I’d like to weigh. So Ive added 250mcg/week in 2 doses of retatrutide which unlike tirzepatide in micro doses tends to INCREASE appetite vs the GLP-1 in Terzepatide / semaglutide / cargulitide drops appetite.
IMHO adding micro doses of some GLP-1 makes sense in the same way HRT makes sense. GLP-1 is just another dropping off hormone and we accept jumping Testosterone (estrogen et al) is health extending, so probably is adding a modest amount of GLP-1. IE micro doses.
At 71 yro, My IGF-1 value before rapa was 109, after 2 yrs rapa 157, after 2 mo of Ipa/Tesa peptides and tested 4 hours after injecting Ipa/Tesa my IGF-1 was 287.
I may be unaware of the downsides of this protocol. But the Thymus rejuvination, muscle grrowing, general good-ness of >>HGH I’ll stick with my modest levels of Ipa/Tesa dosing and consider higher IGF-1 a plus (for now).
And I’m a low responder re LDL vs rapa and also Glucose / Insulin vs HGH/Rapa. So I have not seen any rise in negative blood markers. I hear though this is not universal.
Good luck to all, curt
Do you have your testosterone level when IGF-1 was 109 ng/mL?
Also, do you hypothesize a mechanism why Rapa alone increased IGF-1?
Last, why do you think a hi-IGF-1 phenotype is in your case beneficial? Besides, may your 287 IGF-1 value be a transient caused by the Ipa/Tesa injection? What about fasting IGF-1 far enough away from potential stimulants?
Hi Mccoy, Good questions. I wish I could interspurce research URLs… This is from recollection and opinion.
I’ve been HRT for 15 yr at least. So my T has been 800-1200 the whole time.
Why the 109–> 157 on rapa? Maybe some small organ regeneration of the pituitary??
I quest to be a 40yro forever thus IGF-1 at 287 is good. And yes normal HGH is very spik-y, where IGF-1 has a slower lumpier response and easier to catch a decent measurement. GH wouild need continuos blood monitoring. A 40yro has low GH after food and afternoon, and higher GH early AM pre food. My use of Ipa/Tesa upon waking stimulates GH close to natural.
No doubt if I quit rapa and ipa/tesa my IGF-1 at noon might drop back below 157. Unless true organ regeneration from all the other peptides I’m doing has residual effect. Epitalon, Thymosin A1, TB500, Thymolin, Pinealon. In 2 mo cycles ea. Initially have done all in parallal.
FWIW mitocondrial rejuvination includes; SS-31, MOTSC, urolithin-a, SLU-PP-332(powerful take small dose and watch training by Alex Kikel on youtube before taking). The mitocondrial adjuvants need some study and cycling vs all at once approach. Unless you are extremely low performing then all in parallel may be tolerated. These mito compounds have a U shape dose response.
We all need to listen, study, experiment, measure, repeat, best of luck, curt
I finished the listening today. Fascinating interview. Dr. Fahy is very eloquent and convincing but I wonder, as Kaberlein wondered, why investors are not so interested in his trials.
Towards the end they discuss IGF-1. Strangely, I wasn’t aware that the purpose of the GH administration is to elevate the levels of IGF-1, which apparently causes thymus rejuvenation.
I’ll have to search and see the IGF-1 in the trial participants before and after, if published.
Also, Matt asked about the prevailing models of IGF-1 optimization in the longevity narrative.
Model 1: high IGF-1 is bad because it may cause cancer proliferation. The model supported mainly by the vegan community, but also by eminent gerontologists like Longo and Fontana.
Model 2: IGF-1 is good because it stimulates the immune system, by means, in the hypothesis of Dr. Fahy, of reversing thymus degradation.
I wonder who’s right. Probabaly both, since there is a U-curve relationship with an optimum, meaning that too little of it may affect detrimentally the immune system, too much of it may provide cancer cells with a potent proliferation signal.
In my own situation, I can objectively observe that I have no problems so far with the immune system, which appears to be well regulated. In the last 10 years, I got a fever once a year on average, with 2 days on average per year desiring to be in bed, sleep, and do nothing else. That is not superhuman immunity but I find it satisfactory.
The alternative is to seek elevated IGF-1 but be on the lookout for precocious cancer formation, which can be very tricky. Also, I erroneously believed that GH can alleviate joint pains, but it seems that it is the opposite.
Rationale in favour of IGF-1 levels in Fahy’s first publication. No quantities are reported.
Disclaimer | PMC Copyright Notice
Aging Cell
. 2019 Sep 8;18(6):e13028. doi: 10.1111/acel.13028
Gregory M Fahy 1,
, Robert T Brooke 1, James P Watson 2, Zinaida Good 3,8, Shreyas S Vasanawala 4, Holden Maecker 5, Michael D Leipold 5, David T S Lin 6, Michael S Kobor 6, Steve Horvath 7
In this regard, it must be pointed out that GH and IGF‐1 can also have pro‐aging effects and that most gerontologists therefore favor reducing rather than increasing the levels of these factors (Longo et al., 2015). However, most past studies of aging and GH/IGF‐1 are confounded by the use of mutations that affect the developmental programming of aging, which is not necessarily relevant to nonmutant adults. For example, such mutations in mice alter the normal innervation of the hypothalamus during brain development and prevent the hypothalamic inflammation in the adult (Sadagurski et al., 2015). Hypothalamic inflammation may program adult body‐wide aging in nonmutants (Zhang et al., 2017), but it seems unlikely that lowering IGF‐1 in normal non‐mutant adults can provide the same protection. A second problem with past studies is a general failure to uncouple GH/IGF‐1 signaling from lifelong changes in insulin signaling. Human longevity seems more consistently linked to insulin sensitivity than to IGF‐1 levels, and the effects of IGF‐1 on human longevity are confounded by its inverse proportionality to insulin sensitivity (Vitale, Pellegrino, Vollery, & Hofland, 2019). We therefore believe our approach of increasing GH/IGF‐1 for a limited time in the more natural context of elevated DHEA while maximizing insulin sensitivity is justified, particularly in view of the positive role of GH and IGF‐1 in immune maintenance, the role of immune maintenance in the retardation of aging (Fabris et al., 1988), and our present results.
In the following open access article there is an interesting discussion on the interactions between GH, insulin and IGF-1. I soon collected a couple of basic take-home messages.
1-Both insulin and IGF-1 can bind to and activate each other’s receptors, albeit with reduced affinity [
2-Androgens like testosterone enhance GH action
So in a phenotype like mine, the effect of hi testosterone would be irrelevant, since it’s already included in the measured concentration of IGF-1. It’s a good thing that the T is high, otherwise the IGF-1 would be further lower, too far from the optimum. Besides, insulin contributes to the overall anabolic IGF-1/insulin signal, so its value is a little below average, which contributes to a framework of lower-than-average anabolism and proliferation setup.
The above would describe well what I have been observing throughout the years, a tendency toward catabolism, a difficulty in gaining weight, a strong catabolic signal whenever I go lowcarb, decreasing the IGF-1/insulin signal, which is already pretty low.
Evidently, exercise provides a strong local IGF-1 signal, since I tend to be hypertrophic in musculature rather than hypothrophic.
However, tendons and joints do suffer a little, so the IGF-1 signal may be lower in these tissues, or perhaps there are other causes like difficulties in recovery and so on.
You probably noted it, but in connection with cancer I could not find exactly what IGF-1 levels would be considered high (or low) in the data you provided, including the article from ceu.ox.ac.uk? Do you have that data?
That recalls to mind, something about a form of dwarfism associated with very long life, I read somewhere long ago.
That is true, and I’m searching now, but it seems that the U-curve relationship is kept in the cancer subgroups with but few modifications. For example, this recent article.
The only difference I can see between overall mortality and cancer mortality is that the U curve on the left-hand side increases more slowly in the cancer case than in the total mortality case, indicating that in individuals with lower concentrations of IGF-1 the higher mortality is ofte NOT due to cancer but to other risks.
According to this publication, the optimum would seem to be about 125 ng/ml, rather than 140
