Could anyone with more knowledge in the world of longevity explain the importance of growth hormone to me?
I did the exam twice and my result was zero.
How much should I worry? How bad is it?
Ways to improve naturally?
I fast 17/7, workout always, eat healthy…
I hope someone with more knowledge can jump on this question. What I understand to be true is:
Growth Hormone is transient. It is mostly pulsed into the bloodstream during deep sleep, and then is gone. Any measurement of GH would not necessarily indicate anything
IGF-1 is downstream from GH and it lasts longer so that is the thing to measure.
GH is supplemented by lots of people. Attia is not in favor but at least one of his guests said it’s okay. (I think it was the body builder guy in mid 2023)
For an adult GH is for repair of the body. So deep sleep (when GH is produced) is for body maintenance while REM sleep is for the “mind” — memory and learning.
I think the evidence suggests that, once you reach adulthood, activation of the GH/IGF-I axis is inversely associated with longevity.
Disrupting GH signaling (e.g by impairing pituitary development, or impairing GHR, GHRH, or GHRHR function) can extend mice lifespan anywhere from 23 to 70 percent. Impairing various aspects of IGF-1 signaling can also extend mice lifespan, although the effects are generally of a smaller magnitude. [ref]
Larger dogs live shorter than smaller dogs, and may have up to 28x greater IGF-I levels. Loyal’s IGF-I inhibitor LOY-001 for large dogs is inching closer to FDA approval. [ref]
The studies on GH/IGF-I activity in long-lived humans are harder to interpret.
Long-lived males are enriched for d3-GHR homozygosity. The d3-GHR displays reduced constitutive activity relative to WT, and greater activity in response to GH, which suggests that sharpening the pulsatile nature of GHR activation might be pro-longevity. [ref]
The offspring of female centenarians show about a 1/3 increase in circulating IGF-I, which like the d3-GHR results, seems a bit paradoxical. One possibility is that this uptick is a compensatory response to an impairment of IGF-IR function within this population. [ref]
24 hour AUC of GH is 28% lower in the middle-aged offspring of long-lived families [ref] This and other studies more straightforwardly support the idea that GH/IGF-I is anti-longevity in humans.
The more popular explanations for GH’s anti-longevity effects revolve around cancer (IGF-I is a mitogen in many cultured cell types) and decreased stress resistance (for example, due to impaired protein quality control as a result of excessive mTOR activation). [ref] Another possibility is increased stem cell exhaustion. [ref]
I agree with @jnorm 's post.
Some other threads that discuss this:
Here: IGF-1 inhibitors and lifespan extension?
Here: IGF-1 is Lower for Centenarians
Here: Another (likely) Longevity Drug - Somavert / Pegvisomant
Well it may not be a bad thing. Read this article about an Ecuadorian tribe that has no IGF-1 due to a genetic mutation. They don’t get cancer.
Yes… Peter covered in the following podcast (links below)… the general belief seems to be the lower the basal level of GH / IGF1 the better (in terms of lifespan, and cancer/diabetes/alz, etc.) , but GH probably helps in terms of muscle growth and recovery from injury / damage. So, in theory, a pulsatile approach may be best. But there have not been any real studies on this.
Details (from a body builder type person):
Peter Attia Podcast:
0:21:23-Growth hormone—from extreme use-cases to the more typical—& the misconception that it’s the “elixir of life”
0:29:34-Growth hormone 101: definition, where it comes from, & the challenges of measuring it
0:41:43-Does exogenous growth hormone compromise one’s ability to make endogenous growth hormone?
0:43:51-Use of growth hormone in restoration of tissue during periods of healing
0:51:45-Growth hormone-releasing peptides to increase endogenous GH: various peptides, risks, benefits & comparison to exogenous growth hormone
1:07:12-Role of growth hormone in building muscle & burning fat, as well as its effects on sleep & daytime lethargy
It can also improve skin health, increase bone mineral density, and improve body composition, so for individuals with issues in those areas it might occasionally be a net positive.
I’ve actually taken GHRP-6 in the past, which activates the ghrelin receptor, and can trigger both GH and cortisol release. The ghrelin receptor also stimulates appetite and feeding behaviors and the ghrelin receptor agonist LY444711 appears to extend lifespan in mice, despite evidence that it strongly stimulates the GH/IGF-1 axis. I wonder if LY444711 is acting as a caloric restriction-mimetic, which might offset the increased GH/IGF-1 signaling.
I just came across this old study (accidentally) and it seems relevant to this discussion:
healthy older men who took growth hormone had enhanced reparative collagen deposition during the wound healing process. This action may be clinically useful after selected surgery or trauma in the elderly.
I found this interesting, in the most recent BusinessWeek Longevity article on Minicircle and Bryan Johnson:
Within a few weeks, Johnson flew to the Bahamas for an injection of mesenchymal stem cells—No. 34 on his therapeutic adventure list. Speaking just after that trip from his home in Venice, California, he pulls up a chart showing two years’ worth of data tracking his aging markers and the effects various therapies had on his body. The overall trend line shows his pace of aging slowing, but in one instance a human growth hormone boost designed to rejuvenate his thymus had caused aging spikes. “That was successful because it helped my thymus, but it wasn’t free,” Johnson says. “This aging game is like whack-a-mole.”
Unproven Fountain-of-Youth Injections in Honduras, Anybody?
Need very specific and targeted drugs I guess.
I am convinced that HGH is a powerful longevity hormone and that if used correctly, can extend lifespan. The TRIIM and ongoing TRIIM-X trials have convinced me. Credit to Greg Fahy for doing research on it again.
It’s a shame it’s been vilified and almost impossible to obtain a prescription of. Thank goodness for the black market though.
It seems that GH might be helpful in a pulsed fashion over certain periods for some things. It seems to me the evidence is that its probably not helpful on any ongoing regular basis.
The TRIIM trial only had a few people in it. The TRIIM-X trials haven’t been completed have they? There is a whole biomarker analysis done by the Verdin lab at the Buck Institute that suggests that the change in the biological age measured in the TRIIM trial may just be due to changes in the composition of the cells being meaured, and not actual rejuvenation. So - I still view the data as inconclusive and early.
Eric Verdin explains their research here:
I will watch the video you shared as soon as I can but here is the latest update from Greg Fahy on the TRIIM X trial. So far the results are being replicated. In the TRIIM trial, the best results occurred from month 9 to month 12.
Also if you know who Physionic is, he was amazed by the results too. https://youtu.be/rVoxfABoHh4?si=NDy6UthfI7RfYiL8
Edit: watched the video you shared. Let’s hope they apply it to the TRIIM trial retrospectively. I have to admit I’d be disappointed if it changed the results.
Found your post very informative and interesting especially the above. I think this goes on to suggest that. prolonged exercising is not so good for longevity (since from what I have read it promotes GH).I’ve heard many different things, but Rarely I’ve heard centenarians saying that the reason for their long life was the exercising. Most tend to say daily walks (apart from other things of course)
I think the situation is more that GH activity during early life is negatively associated with lifespan. Drastic reductions in signalling, IIRC, do still prolong life in old animals, but to a far smaller degree than when done, even temporarily, in young ones. Unfortunately I don’t have comprehensive references at hand right now. Consider spiralling out from here.
That’s a good point, most of these GH/IGF-1 mutant studies are not conditional, so the deficiency starts at t=0. My point (worded rather poorly) was that inhibiting GH/IGF-1 axis prior to adulthood isn’t desirable in humans, given that we generally value height.
The study you linked is quite interesting. They knocked down liver IGF-1 is at 5 months (this is considered adulthood) and in females it gave median lifespan extension and trend towards max lifespan extension. No significant changes in male lifespan. Good and bad functional changes (reduced kidney disease in males, decrease in overall disease burden in males, increased liver cancer in males and females, impaired spatial learning in males).
One other thing is those mice compensate by drastically elevating GH and this might mask some of the benefits of IGF-1 knockdown. For example, GH induces insulin resistance, an effect that may be independent of IGF-1.
Another study knocked down GHR at 6mo in mice and found extension of median and max lifespan but only in females. Whereas only the males showed increased insulin sensitivity, reduced markers of fat and protein oxidation in subq fat and liver, and reduced cancer and overall disease burden.
The circulating GH was even higher in these mutants (~100ng/mL at 22mo), whereas your study had ~30ng/mL and ~10mg/mL in the mutants and controls, respectively. This high circulating GH coupled with incomplete GHR knockdown in tissues like skeletal muscle and heart makes me wonder if these tissues were being exposed to supraphysiological activation of GHR intracellular pathways.
Overall, I think the evidence points toward increased GH/IGF-1 being bad for longevity, even in adulthood. Although the mice data seems to indicate that lifespan extension from reducing this axis is more likely in women (especially if started in young adulthood). I think if body composition was also kept in check, the benefits in the GHR conditional knockdown might be more extensive, as these mice are significantly fatter.
Will certainly help once we have more info on Loyal’s LOY-001. Would also be nice to see mouse studies on Pegvisomant, which would less drastically inhibit GHR signaling than the conditional GHR knockdown, and more uniformly inhibit GHR signaling across tissues.
I vaguely remember that Eric Verdin said at the conference that they contacted Fahy to see if they would work with the Buck to re-evaluate their data with their new biological clock to see if the results changed. He didn’t want to do it, Eric seemed to suggest as I remember it. No idea why.
New research on growth hormone / IGF1
Zahida Sultanova, Aykut Shen, Katarzyna Hencel, Hanne Carlsson, Zoe Crighton, Daniel Clifton, Alper Akay and Alexei A Maklakov
bioRxiv. posted 23 December 2023, 10.1101/2023.12.22.573079
Just reviewing this opinion paper on growth hormone and longevity from 2022…
This caught my eye:
A reduction in IGF-1 signaling does not alter life span at nearly the levels observed in reduced GH signaling mutants (5% vs 40%–70%, respectively). In complete agreement, a metanalysis including 42 survival studies examined reduced somatotropic signaling (GH, IGF-1, insulin receptor substrate [IRS]) and found that mice with mutations that alter GH signaling exhibited greater relative reductions in mortality compared to those with mutations that affected either IGF-1 or IRS (52). This report concluded that reductions in GH signaling “robustly” increase median life span, exhibit low heterogeneity in the life-span response (5.6% vs IGF-1 34.1% and IRS 47.2%), and are not sex- or control strain-dependent (52). In contrast, reductions in IGF-1 signaling preferentially extend life span in females and short-lived strains of mice. Moreover, life span is not increased in transgenic mice expressing a GH antagonist where levels of circulating IGF-1 are decreased, and insulin levels and sensitivity are not altered (53). Overall, this evidence supports our work and others that strongly propose that reduced GH rather than the secondary reduction of IGF-1 provides beneficial effects on aging and is the key to longevity in mammalian systems perhaps through stress resistance, reduced inflammation, and insulin sensitivity.
Although IGF-1 is likely the major determinant of life span in invertebrates, it is GH that affects multiple physiological processes that significantly affect longevity in mammals. Keys that factor into the influence of growth hormone on longevity may be the major role it plays metabolically in vertebrate organisms stemming from the wide expression of GH receptors centrally and peripherally and its regulation of circulating IGF-1 levels among others. In addition, growth hormone’s influence on aging trajectories and longevity is not limited to early- or late-life actions (89,90).
Papers referenced in this article:
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But localized (vs. systemic) or short-term GH may provide benefits, it seems:
Conclusion: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.