https://academic.oup.com/jcem/article/107/7/1906/6562793?login=false
The 2024 study by Lasher et al. aims to clarify the specific role of growth hormone (GH) in longevity. While previous research showed that interrupting the GH/IGF-I signaling axis extends mouse lifespan, those models often featured confounding factors, such as deficiencies in multiple hormones (like prolactin and thyroid-stimulating hormone). To address this, the researchers evaluated mice with a targeted knockout specifically of the GH gene.
Key Findings on Lifespan
Overall Extension : Mice with isolated GH deficiency (GH knockout or KO mice) on a mixed genetic background demonstrated a 21% extension in median lifespan compared to wild-type (WT) littermates.
Sex Differences : Male KO mice experienced a 27% median lifespan extension over WT males. Female KO mice displayed a statistically significant, though more modest, 14% lifespan extension.
Physiological and Metabolic Impacts
Body Composition : Consistent with previous reports, GH deficient mice had reduced body weights but displayed disproportionately higher body fat as a percentage of total weight.
Fuel Utilization : KO mice exhibited altered nutrient utilization, showing a reliance on fat oxidation and a reduced reliance on glucose oxidation to meet energy demands.
Glucose and Insulin Dynamics : The altered glucose metabolism was accompanied by impaired glucose tolerance in both males and females. Notably, enhanced insulin sensitivity was only observed in male KO mice.
Conclusion The study concludes that isolated GH deficiency is directly responsible for extending both average and maximum lifespan in mice. This longevity is accompanied by specific physiological trade-offs, namely excess adiposity and impaired glucose metabolism, reinforcing the role of GH as a major regulator of mammalian aging.
Patients with acromegaly have high levels of growth hormone; their overall standardized mortality rate is approximately twice that of the general population, and their average life expectancy is shortened by about 10 years.
The effects of specific diets and fasting regimens on aging and cancer appear to be mediated, in part, by reducing the activity of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis.
Based on these observations in humans and other species, we hypothesized that lower IGF-1 levels are predictive of extended survival in generally healthy nonagenarians.
So basically, this means that mice that were deficient in GH lived longer, in other words taking GH may negatively affect longevity? Am I reading this correctly?
As I have observed bodybuilders at the gym, HGH has always intrigued me. It definitely helps with gaining muscle mass in the elderly. However, I have never pulled the trigger because of safety concerns for the elderly. Lest I inadvertently off myself.
Claude:
HGH in Elderly Males — Potential Benefits
As men age, natural growth hormone production declines significantly (sometimes called “somatopause”). Studies have shown HGH supplementation can produce some measurable changes:
Increased lean muscle mass — one of the more consistently observed effects
Reduced body fat, particularly visceral fat
Improved bone density — potentially reducing fracture risk
Better exercise capacity in some studies
Improved skin thickness and some quality-of-life markers
However, a critical caveat: these changes don’t reliably translate into functional improvements like greater strength, better physical performance, or longer life. The landmark 1990 Rudman study in the NEJM that ignited interest in HGH for aging was small and short-term, and follow-up research has been far more mixed.
The Cancer Risk Question — This Is the Serious Concern
This is where HGH supplementation becomes genuinely worrying, particularly for older men:
HGH stimulates IGF-1 (Insulin-like Growth Factor 1), which promotes cell growth and proliferation throughout the body — including potentially cancerous cells
Elevated IGF-1 levels have been associated in epidemiological studies with increased risk of prostate, colorectal, and breast cancers
HGH is absolutely contraindicated in anyone with active cancer or a history of cancer, as it could accelerate tumor growth
Men with undiagnosed prostate issues (very common in elderly males) could be at particular risk
Long-term safety data in healthy elderly populations is still limited
Some population studies also note that people with naturally lower IGF-1 (such as those with Laron syndrome) have remarkably low cancer rates, suggesting the IGF-1 pathway plays a meaningful role in cancer development.
Other Notable Risks
Beyond cancer, HGH supplementation in elderly men carries other real risks:
Edema (fluid retention) and joint/muscle pain — very common
Carpal tunnel syndrome
Insulin resistance and increased diabetes risk — significant concern
Gynecomastia (breast tissue enlargement)
High cost with most insurers not covering it for anti-aging use
The Bottom Line
Most major medical organizations, including the NIH and the Endocrine Society, do not recommend HGH supplementation for healthy elderly men as an anti-aging intervention. The benefit-to-risk ratio is unfavorable — the functional benefits are modest and inconsistent, while the risks (particularly cancer promotion and metabolic disruption) are real and potentially serious.
This article doesn’t answer this question for mice or humans . The study was done on gh deficient mice, not normal ones. Being gh deficient genetically is different than having low gh.
A large number of studies have shown that individuals with lower growth hormone levels exhibit features of premature aging, which may be reflected as accelerated epigenetic age. However, both humans and mice with low growth hormone levels show a significant extension in lifespan. Conversely, growth hormone injection can reduce epigenetic age but may ultimately shorten lifespan, as demonstrated in studies of both mice and humans with high growth hormone levels. My current recommendation is to approach this rationally and avoid taking growth hormone rashly simply because it increases thymus volume or reduces epigenetic age. Carefully consider the potential consequences.
In the real world, many things are not linear. My inference is that growth hormone can extend healthspan but will shorten overall lifespan.
A simple example is lead. In the early stages of lead poisoning, it excites the sympathetic nervous system, creating an illusion of being energetic and having increased libido. However, long-term use will drain your lifespan. This example may not be ideal, but given the context, you should understand what I mean.
Therefore, we need to focus on endpoint indicators—the core metrics are lifespan or all-cause mortality. The simplest example is Professor Michael Lustgarten, who took niacin and saw a significant acceleration in his epigenetic age, yet multiple large-scale trials have shown that niacin reduces all-cause mortality. Don’t make decisions based on these so-called indirect markers; the predictive power of such indirect markers is quite poor.
I’ve looked at this extensively… and after my initial enthusiasm for IGF-1 inhibition I’ve become much less optimistic. It seems most likely of value (i.e. the largest effect) during a short time early in life … precisely when you probably don’t want it because you end up small and short… Laron Dwarfs live to age 100 on average, without cancer or Alzheimers, but they are about 4 feet tall and tend to be rather obese (though it doesn’t seem to hurt them much). 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.
In this study, done by Richard Miller’s team, they found that only a few weeks of GH injections reversed many aspects of the longevity phenotype. I’m not sure if there have been any studies yet on low-GH / IGF1 levels implemented later in life.
The exceptional longevity of Ames dwarf (DF) mice can be abrogated by a brief course of growth hormone (GH) injections started at 2 weeks of age. This transient GH exposure also prevents the increase in cellular stress resistance and decline in hypothalamic inflammation characteristic of DF mice. Here, we show that transient early-life GH treatment leads to permanent alteration of pertinent changes in adipocytes, fat-associated macrophages, liver, muscle, and brain that are seen in DF mice.
…
Thus, many of the traits seen in long-lived mutant mice, pertinent to age-related changes in inflammation, neurogenesis, and metabolic control, are permanently set by early-life GH levels.
Yes, this is a limitation, so I found another more comprehensive study.
The study showed that growth hormone injection significantly shortened the lifespan of male dwarf mice, but had no effect on female dwarf mice or normal mice.
This at least proves that growth hormone injection does not extend the lifespan of normal mice, and shortens the lifespan of other types of mice.
Healthy elderly individuals receiving GH therapy have a significantly higher risk of developing soft tissue edema, joint pain, carpal tunnel syndrome, and gynecomastia, as well as a slightly higher risk of developing diabetes. Impaired fasting glucose.On the basis of this evidence, GH cannot be recommended as an antiaging therapy.
Bro, you might be better off using the literature to communicate or refute—that would make the discussion more meaningful. Otherwise, having me constantly prove something that is widely accepted is very uninteresting.
At present, the side effects of growth hormone may be avoidable with metformin, but the most critical point is that growth hormone’s effects on lifespan are entirely negative—in both humans and mice. Yes, I’m talking about endpoint indicators. Perhaps what you need to do is use the literature to support your argument. Growth hormone itself is a prescription drug, and perfect studies on the healthy populations you care about are very scarce. Therefore, we need to make judgments even when the evidence is not fully conclusive, rather than constantly saying that the trials are not perfect enough.
According to your understanding, injecting growth hormone can restore the thymus, and people with a healthy thymus have significantly lower all-cause mortality and cancer risk. However, the current academic debate is whether injecting growth hormone increases cancer risk. If it truly extended lifespan, we would have observed that in mice and humans long ago—instead of seeing a large number of negative studies showing shortened lifespan and increased risks of various diseases.
I didn’t refute anything. I just asked you to clarify what the study (you had posted) says. I wasn’t aware that it was widely accepted HGH is detrimental to longevity. Plus, judging by the TRiMM protocol we were led to believe that it actually generates thymus and as such helps with longevity. so now I’m confused LOL
I think you guys are talking about two different things.
The TRIIM trial using GH (among other agents) to restore the thymus was a relatively short-term trial… The duration of recombinant human growth hormone (rhGH) dosing in Dr. Gregory Fahy’s TRIIM trials is 12 months (one year) . This timeline applies to both iterations of the study. I view this as a relatively short pulse of exogenous GH dosing, given an average 80 year lifespan for people.
At the same time, I think that the evidence that higher levels of GH/IGF1 increase risk of cancer is pretty good… Laron Dwarfs (who have a defect in the GH receptor gene, so don’t recognize GH) don’t get ANY cancer despite smoking, obesity, diet, etc.
And we also know that a typical person with typical IGF-1/GH and typical diet, DOES get cancer at a reasonably high and well-documented rate.
If a typical person with typical IGF-1/GH and typical diet, periodically doses with exogenous GH then yes, the risk of cancer likely goes up a bit, but if you look at the total “area under the curve” of total IGF1/GH dosing over the lifespan of the person, and use that as a rough guide for risk of cancer, then its likely a very small increase in risk.
Another argument against GH being a significant risk for increased cancer risk is because GH injections became popular in the “anti-aging” crowd in the USA back in the 1980s, and many thousands of people have (and continue to this day) take exogenous GH injections. There has been no documented (or anecdotal) reports of increased risk of cancer, so while it may be there, it doesn’t seem to be a very significant or noticeable increase.
Now, I stick to training in a fasted state – the most powerful natural stimulus. Possibly combined with arginine pyroglutamate and lysine, to increase endogenous GH secretion. I tried that combinations decades ago.
Of all physiological stimuli, sleep and exercise are the most powerful non-pharmacological triggers of growth hormone release. The exact mechanisms are not yet fully established, but several candidates have been identified: neural activation, direct stimulation via catecholamines, lactate and/or nitric oxide, and changes in acid-base balance. The strongest candidates appear to be afferent nerve stimulation, nitric oxide and lactate.
Claude with references: (some are redundant or already posted)
Fasting Alone Raises HGH
During fasting, more sporadic GH bursts occur, leading to an overall 3-fold increase in GH area under the curve compared to baseline. PubMed This is a well-replicated finding across multiple studies.
Exercise Alone Is a Potent HGH Stimulus
Sleep and exercise are the most powerful non-pharmacological stimuli for HGH secretion. Resistance training results in a significant exercise-induced GH response, with load and frequency being key determining factors. An exercise intensity above the lactate threshold for a minimum of 10 minutes appears to elicit the greatest stimulus to HGH secretion. PubMed This is why high-intensity resistance training and HIIT are particularly effective.
The Combination — Fasted + Exercise
Research published in the Journal of Clinical Endocrinology & Metabolism found that during exercise, GH concentrations rapidly increased to greater than 10 ng/ml, and that myocellular GH signaling is stimulated by both exercise and fasting in terms of STAT5 phosphorylation and IGF-1 gene expression. PubMed
Fasting has been shown to augment GH secretion, and research suggests there may be an interaction between fasting and exercise that further amplifies the GH response — with longer fasting intervals before exercise potentially producing slightly higher integrated GH concentrations. American Physiological Society
The Important Caveat — HGH Spike vs. Functional Benefit
This is where it gets nuanced. While fasted resistance training does induce GH release with a likely anabolic effect, research from the University of Virginia suggests the body may also be reacting to counter the catabolic impact of fasted exercise — meaning the HGH spike may partly be a stress response, not purely an anabolic signal. NFPT
In other words, a higher HGH reading after fasted exercise doesn’t automatically translate to more muscle growth or fat loss compared to fed training. The acute hormonal spike is real, but its downstream functional significance is debated.
How can we summarize the present understanding and use this information to suggest possible anti-aging interventions? Physiological action of the amounts of GH normally secreted by the pituitary is critically needed for growth and maturation and enhances reproductive potential but may also limit life expectancy.
As early as the 1990s, a large number of people were using it for anti-aging purposes, but no significant improvement in endpoint indicators was observed. Instead, there was a constant need to prove that growth hormone does not cause cancer. In my view, this in itself is a failure.
Significant improvement in the thymus means that the risk of cancer is greatly reduced, rather than requiring the reverse proof that growth hormone does not increase cancer risk. That’s all I have to say — you can now synthesize all the information and make your own judgment.
The dose ends up being very important as does the monitoring.
If no adverse metabolic effects (and often beneficial ones), improved T cell profile, a little bit better lean body weight, and IGF-1 that isn’t in the higher %tiles … my take on it is that it’s a sensible thing.
I’ve moved over to a combination of CJC-1295/Ipamorelin/Tesmorelin in a 1:1:2 ratio. It’s tough to really be certain on how much HGH is being generated. Looking at change from baseline IGF-1 +/- IGFBP-3 are methods. At least the cost isn’t too bad as IGF-1 is $20 and IGF binding protein 3 is $45.
The question is what would trigger one to stop, as this is a normal hormone that at least in younger years is there all the time (in a pulsatile fashion - which this combination of peptides are supposed to mimic)?
I do have a reasonable number of patients who choose to do this, and I’m yet to see anything concerning, and generally see good things, and people who aren’t keen to stop this, when taken at sensible doses.
The dose definitely makes the poison here - high doses are very detrimental to longevity. I suspect the folks that benefit the most are those with an initial low IGF-1.
I’d love folks thoughts on this, as this is yet another area where we don’t have the studies we’d actually like that would point us to clear efficacy and clear lack of significant risks.