The use of HGH for longevity seems counterintuitive to me. We take rapamycin intermittently to suppress mTOR complex 1, thereby downregulating growth and development signaling, and enhancing autophagy the combination of which is the likely explanation for the longevity benefits of rapamycin.
Alternatively, a function of growth hormone (HGH) is to promote cell and tissue growth, and a key component of these effects is the stimulation of protein synthesis.
Iām curious about the simultaneous use of Tesamorelin and cjc (no dac, I assume) , since they are both ghrh and thus both compete for the same receptors. Doesnāt that seem redundant?
This is one of I believe five studies in humans showing that HGH improves heart failure when you have a growth hormone deficiency. Iām not driving my GH intentionally low because of some rat studies
The SAGhE data indicate that for patients without severe underlying diseases (isolated growth failure, IGF), the cancer standardized mortality ratio (SMR) is 0.8 (95% CI: 0.4-1.6) , and the standardized incidence ratio (SIR) is 1.0 (95% CI: 0.6-1.4). Although the absolute SMR value of 0.8 appears to be less than 1, its confidence interval crosses 1.0 (reaching up to 1.6). Statistically, this indicates that their mortality rate is not significantly different from that of the general population. For patients with other underlying diseases but no prior cancer history, the overall cancer incidence (SIR=1.4) and mortality (SMR=2.2) in this group show a statistically significant increase.
From this, we can conclude that the best-case scenario is that cancer incidence or mortality does not increase, but it also does not significantly decrease. Currently, across all endpoint metrics regarding lifespan, although growth hormone can regenerate the thymus, it has not demonstrated any direct impact on lifespan. This concludes my analysis.
To reiterate: if Growth Hormone (GH) constantly requires proof that it doesnāt increase cancer risk or mortality, then it is inherently flawed. In the field of anti-aging, a lack of progress is equivalent to a setback. If there were even a shred of evidence that GH extends the lifespan of nematodes, fruit flies, or mice, we might consider it valuable. However, the scientific evidence suggests exactly the opposite: statistically, downregulating the GH/IGF-1 signaling pathway is what actually demonstrates lifespan extension.
A famous historical example is niacin. Despite its effectiveness in lowering Low-Density Lipoprotein Cholesterol (LDL-C) levels, it failed to reduce the risk of cardiovascular events. Consequently, current clinical guidelines no longer recommend niacin for cardiovascular disease prevention.
The most critical factor to remember is the hard endpoint, rather than becoming obsessed with surrogate markers. The clinical significance of these indirect indicators is extremely limited, yet some forum members remain fixated on them.
Last time, regarding Imeglimin, I simply stated that there are currently no dedicated Cardiovascular Outcome Trials (CVOT) with cardiovascular death or Major Adverse Cardiovascular Events (MACE) as the primary endpoint, and that priority should be given to medications recommended by the guidelines. To my surprise, a so-called āsenior forum memberā reacted with emotional attacks. I was merely stating what any responsible physician would say.
Exactly. Kaeberlein brings this up. And, Fahy says no evidence of increased cancer risks. The thymus rejuvenation actually builds immunity response to cancer.
A meta-analysis published in 2011 (including over 10,000 patients) showed that the effect of GH on cardiovascular disease mortality follows a U-shaped curve, meaning that both excessively high and excessively low IGF-1 levels increase cardiovascular mortality. Compared with the āmedium levelā of IGF-1, the hazard ratio (HR) for all-cause mortality in the ālowest groupā was 1.27 (95% CI = 1.10ā1.46), while the HR in the āhighest groupā was 1.18 (95% CI = 1.04ā1.34). The lower bounds of the confidence intervals for both groups were greater than 1.0, indicating statistical significance.
This confirms at the data level that both too high and too low IGF-1 levels are indeed associated with increased all-cause mortality. However, with HRs ranging from 1.18 to 1.27, the association is of low-to-moderate strength, suggesting that the impact on overall mortality is limited. Even so, it can still be concluded that high levels of growth hormone, at best, have neither beneficial nor harmful effects on lifespan, and at worst, increase all-cause mortality.
Just to add ā many people may not understand the relationship between GH and IGF-1. I donāt mean to preach ā Iām just briefly explaining it to those who donāt know. IGF-1 is mainly produced by the liver under the stimulation of GH, with small amounts also secreted by tissues such as muscle and bone. GH is rapidly metabolized in the blood, with its concentration dropping by about half every 20 minutes. In contrast, IGF-1 mostly exists in bound forms in the blood, is more stable in the body, and can reflect recent GH activity levels.
Another interesting realālife phenomenon is that growth hormone injections are often used to increase a childās height, yet scientifically speaking, shorter stature is associated with longer lifespan. Yes, growth hormone can make you stronger and bring your physical metrics more in line with modern aesthetic standards, but is it truly beneficial for longevity? In all the research so far, I have never seen evidence of that. This might give you something to think about.
Later in life it seems pulsed GH may improve quality of life, with some small negative impact on longevity and in other areas (likely dose-dependent), but perhaps a trade-off many people would take willingly.
Yes, that is the key point. If a person continues to be mentally and physically strong as they age, then they are very fortunate.
But, for many of us in the older age range there is the inexorableāand sometimes rapidādecline of both body and mind. If the use of HGH can potentially improve the quality of life in those remaining years, I view it as preferable to becoming old, frail, and cognitively impaired sooner than I would like.
Or, another way to put it is quality of life versus quantity of life.
The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species.
Regarding the effects of growth hormone on lifespan, nearly all studies show negative outcomes ā yes, including allācause mortality, cancer risk and mortality, and ultimately lifespan itself. Growth hormone can improve some indirect markers, but the significance of these markers is extremely limited. To give another simple example: the Framingham Heart Study found that for every 1 mg/dL increase in HDLāC, the risk of coronary heart disease decreased by 2ā3%, leading many to believe that raising HDLāC protects the cardiovascular system. However, observational studies have a fatal flaw: association does not equal causation. This is why CETP inhibitors can substantially raise HDLāC, yet many of these drugs provide no cardiovascular benefit and even slightly increase allācause mortality. I believe the many examples Iāve provided can help raise awareness and reduce the obsession with indirect markers.
āEvery man desires to live long,ā wrote Jonathan Swift, ābut no man would be old.ā He was right, but the fountain of youth has proved illusory. GH does not appear to be either safe or effective for young athletes or healthy older men.
Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing
Growth hormone has been around for decades, but thereās a reason everyone is intimidated by itāand as for why, Iāve already explained it far too many times. The elevated risk of prostate cancer that this MD is concerned about is the exact same concern Greg Fahy himself had at the start of the TRIIM trial. Because of this, Fahy specifically evaluated short-term prostate cancer risk markers during the study. AAs I mentioned earlier, all currently available data in the medical field regarding overall cancer risk, cancer mortality, and all-cause mortality either show no net effect (neither beneficial nor harmful) or are negative. This is why I say that while growth hormone can regenerate the thymus, it does not necessarily mean you will reap the actual benefits of having a functional thymus.
Definitely, if you have familial cancer genetics, potential prostate cancer or have had cancerā¦ lots of things are off the table for you.
I am trying to address the normal, healthy population on this site. As always, each person is responsible for testing and knowing their health situation. A fair balance of risks and rewards always needs to be in oneās health choices and treatments.
Rapamycin is helpful in clearing potential cancer cells. So that is a plus of using it for the past 4.5 years. Finasteride is also a great medication for prostate cancer prevention. Been on it 34 years. My prostate is still walnut sizeā¦ like a guy in his 20ās.
Fasting levels of IGF-I, free IGF-I, IGF-II, IGFBP-3, and insulin increased significantly within 3 months of GH treatment, whereas IGFBP-1, IGFBP-2, and IGFBP-6 showed no change.
You guys make the judgment based on the paper itself
Yes, growth hormone can make you stronger and bring your physical metrics more in line with modern aesthetic standards, but is it truly beneficial for longevity?
The developmental aspects of GH signaling are interesting and almost certainly contribute to its interaction with lifespan, whether through increased cellularity (more ālotteriesā where cancer can win), pleiotropy (e.g the rates of melanoma scale much faster with height than other skin cancers, due to height and mole coverage/formation being correlated), increased stress on the cardiovascular system (us tall folks work that much harder against gravity), or any of the other myriad possible mechanisms.
That said, these considerations arenāt as relevant for the acute and shorter-term effects of GH signaling, which is what concerns someone taking GH in adulthood. Does the increased immune surveillance from thymic reconstitution offset the increased mitotic load? Does the decreased adiposity outweigh the increased insulin resistance? What about the increased recovery, bone density, and skin quality? All of these are become increasingly important in old age where they naturally fail. These are the questions we care about here.
Iām not really taking one side or the other, as I think this is quite an open question. This is despite what the evidence in animal models says. Which, keep in mind, the interactions of growth hormone with lifespan in animals have mostly been analyzed with genetic knockouts. This constitutive loss of signaling is not the case in humans, where weāre mostly interested in a pulsatile administration.
FWIW, I do think that in time we will switch from GH to its downstream signals (in particular FGF21) which are actually regulating the thymic maintenance.
Patients with acromegaly generally have elevated GH and IGF-1 levels, and consequently possess a thymus volume that their peers do not have. But so what? If their GH and IGF-1 levels are not suppressed, their life expectancy is typically ten years shorter than that of normal individuals. If you read my article carefully, you will understand that although growth hormone can regenerate the thymus, it does not mean you can reap the associated benefits. The correlation is far weaker than you imagine. Growth hormone has been around for decades, and the data from these decades consistently show that at best, it has neither benefits nor harms; at worst, it is associated with higher all-cause mortality and cancer risk. Stop obsessing over these surrogate indicators. I have already explained the specific reasons multiple times before.
This is an example I often cite, and there are many similar cases in medicine. Iāve noticed that many people on the forums find it difficult to grasp this point: focus on hard endpoints rather than surrogate indicators; otherwise, most will quickly fall into misconceptions. Iāve also seen many people on the forums obsess over their drug combinations covering all anti-aging pathways. I can only say that this is utterly disastrous.
If these people had experience in drug development, they would know that theoretical anti-aging targeted pathways are still a long way from practical application. They are unaware that too many drugs have failed in Phase III clinical trials. Sometimes, what you think is an anti-aging pathway can actually be fatal. This is the importance of human clinical trials, which is why hard endpoints will always be the primary factor.
Of course, I made the same mistake at the beginning. My initial drug combination was far more extensive than Bryanās. But after reading tens of thousands of papers and learning from them ā not just reading abstracts; many people know that I often upload full papers for those who donāt have access ā I have now developed an optimal anti-aging compound combination. This took far more time than one might imagine. Of course, Bryan is doing the same thing. At this point, Bryan and I may be at two extremes: he has perfected the approach to indirect markers, including epigenetic age, while I have perfected the approach to hard endpoints. This is why Bryan gave up rapamycin, whereas I place rapamycin at the top of my priority list.
Hmmmā¦ acromegaly patients genetics, to normal patients like meā¦ who are taking HGH for IGF-1 increases for a short termā¦ seem like apples to oranges.
And this: Long Dismissed in Adult Health, the Thymus May Be Critical for Longevity and Cancer Treatment | Mass General Brigham 9