A Review of Growth Hormone in Aging

The author of this open access review of the study of growth hormone in aging is one of the eminent experts in this part of the field, noted for work on various loss of function mutant mice, lacking either functional growth hormone or functional growth hormone receptor genes. The current record for mouse longevity is held by a growth hormone knockout variant: these mice wouldn't survive in the wild, as they are small and vulnerable to cold, but they live 60-70% longer than their unmodified peers in the laboratory.

It is well documented that circulating levels of GH decline with age in various mammalian species, including humans, domestic dogs, and laboratory rodents. Yet in laboratory mice, disruption of growth hormone (GH) signaling leads to a remarkable extension of longevity. These findings were hard to interpret and were originally received with some skepticism because they implied that normal actions of a hormone have significant 'costs' in terms of longevity, and that a gross defect in the functioning of the endocrine system can have striking benefits for healthy survival. However, the evidence that absence of GH signaling extends longevity of mice is strong, reproducible, and now generally accepted.

Several aspects of the findings in GH-deficient and GH-resistant mice deserve particular emphasis. First, the significant extension of longevity in these animals is reproducible and not limited to a particular laboratory, diet, or genetic background. Second, lifespan is extended in both females and males. Third, extension of longevity is associated with a similarly striking extension of healthspan. Fourth, the magnitude of the increase in longevity exceeds the effects of most genetic, pharmacological, or dietary interventions that have anti-aging effects in mice.

A recent study examined longevity of mice lacking both GH and functional GH receptors. While these tiny 'double mutants' were remarkably long-lived compared to their normal siblings, they did not live significantly longer than mice lacking only GH or only GH receptors. In females, survival curves of GH-deficient Ames dwarf, GH-resistant GHRKO, and 'double mutant' (df/KO) animals were nearly identical.

The importance of GH signaling in the control of murine lifespan is further emphasized by the evidence that disruption of signaling events 'downstream' from GH and its receptor also extends longevity. Early findings of extended longevity of female mice heterozygous for the deletion of IGF-1 receptor were confirmed and extended in further studies. Major increase of longevity was seen in mice in which amount of bioavailable IGF-1 was reduced at the tissue level by germline or adult disruption of the gene coding for pregnancy associated plasma protein A, an enzyme degrading IGF-1 binding protein. Significant and reproducible extension of longevity was also produced by pharmacological suppression of the activity of mechanistic target of rapamycin, a kinase regulated by GH and IGF1.

Importantly, conclusions concerning pro-aging effects of normal or elevated GH based on studies in mutant, gene knockout, transgenic, or drug treated mice appear to apply to genetically normal mice and to other mammalian species. Multiple studies reported negative association of adult body size (a strongly GH- and IGF-1-dependent trait) with longevity in comparisons of different mouse strains, selected lines, and individual animals.

Link: https://doi.org/10.5534/wjmh.180018


There's never a free lunch, huh? Growth hormone keeps us young, helps us sleep better, recover better from stress, sheds visceral fat, makes our skin softer and hair more lush. But it sends us earlier to our grave, at least for murine species.

It's starting to become extremely frustrating for me to have experienced what youth was like and realize that it was fleeting and can never return. How cruel is nature to make you experience your peak early on in your life and then torture you with a slowly failing body for decades thereafter?

I need a drink.

Posted by: DdR at May 18th, 2018 8:53 AM

Natural Genetic restriction of growth hormone was recently found to extend male lifespan about 10 years in about 5% of humans throughout most of the World (Ben-Averaham, Science Advances, The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity). The males who have the deletion (d3/d3 in at least 2 SNP's) are on average an inch taller than their male siblings. I happen to have inherited the genetic condition and am about 2 inches taller than my brother. But my brother has many FOX03 longevity SNP's (as do I) that cause those to have it to be shorter than normal, but have exceptionally long lifespans.

Posted by: Biotechy at May 18th, 2018 9:41 AM

PS: The study I refer to above was published in 2017 (sorry I forgot to include that). The reference is also found in the article. The GHR gene SNP's I refer to are rs45901833 and rs6873545 with being homozygous for the CC alleles in both cases conferring the 10 years increased lifespan in males, and being about 1 inch taller in stature.

Posted by: Biotechy at May 18th, 2018 9:58 AM

I suspect this relates to autophagy. Increased growth hormone increase metabolism. Increase metabolism, in the absence of increased autophagy, results in a shortened lifespan. However, if you workout, which increases HGH production naturally, and do the other things to increase autophagy, then you should come out ahead in terms of both "youth" as well as lifespan.

At least that's how I look at it.

Posted by: Abelard Lindsey at May 18th, 2018 11:54 AM

Would highly recommend reading above link. Seems like all the pathways that aim to slow down ageing converge on one point ncl-1 which results in a smaller number of ribosomes ultimately. So if you believe ageing is damage driven then you could say they are all slowing protein production kind of like taking the foot off the accelerator and therefore slowing down damage accumulation. If this is true Sens continues to be right and we should repair damage as the most effective path. Also all the inferior slow ageing approaches could perhaps just concentrate on increasing ncl 1 expression?

Posted by: David luck at May 18th, 2018 12:24 PM

By all pathways I should clarify these include caloric restriction, insulin signaling motor etc etc see the diagram in the link. Seems like a A bit of a breakthrough result considering all the millions spent on rapalogs etc which never seem to be able to explain why rapamicin slows ageing due to the spaghetti of genetic effects which this article may actually provide the key insight. https://m.phys.org/news/2018-05-weve-nucleolus-left-school.html

Posted by: David luck at May 18th, 2018 12:35 PM

Don't forget that your body was never meant to last that long. everything after 40 is just a free ride...
For the stone age, assuming the age of first birth is 13-15 then at 40 you are grand-granpa.... If you live up to 80 you are incomprehensibly old

Posted by: cuberat at May 18th, 2018 12:42 PM

Okay, this is sobering news to me. A little over a year ago I caught Ronda Patrick's video on how to raise your HGH levels as well as via hyperthermic conditioning (i.e. heatshock therapy):


Since then I've spent 20 minutes in the sauna five days a week. It does help a lot with my workout recovery but the notion that I may be shortening my lifespan is rather disconcerting.

Posted by: Michael at May 21st, 2018 9:34 AM

Patrick has a video on the HGH/IGF-1 performance/longevity tradeoff:

Inducing heat shock response has been shown to increase lifespan in flour beetles. I remember first learning of this as an undergrad and regretting moving out of the fancy apt. building that had the sauna - though I had to share a 1 bedroom with three other people to afford it. Does sauna induce the hsr and increase lifespan in humans? idk {shrug}

Posted by: CD at May 21st, 2018 3:54 PM

I read this and it was of interest to me as one of the thymonauts, that is, subjects in Greg Fahy's trial using growth hormone to restore immune function. Author may be an expert but is seemingly unaware of Fahy's research and seriously mischaracterizes benefits of HGH e.g. regeneration of immune function and doesn't even mention the potential to mitigate the undesirable side effects such as diabetes. Hmm.

On a personal note, I no longer have massive allergies to tree and grass pollen. So to say there are no benefits is just nonsense. Serious nonsense.

Posted by: Peter Rothman at May 24th, 2018 8:48 AM
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