Growth Hormone: A Physiological Fountain of Youth?

Summary: Need more data. Doesn't look encouraging.


Paper by Jason Wolfe in Journal of Anti-Aging Medicine, Volume 1, Number 1, 1998, published by Mary Ann Liebert Inc (it always is, so consider that your final notice)

This is a review paper of the use of growth hormone with respect to preventing/reversing aging. The idea of why it's worth trying is simple: growth hormone (GH) triggers building of protein and growth of tissue in general. It generates muscle, grows your thymus (immune system trainer/storage) and shrinks adipose tissue (fat). Old people become smaller and their tissues shrink. They are also made of fat (40% in over 75s vs 20% in the young and spritely). Their growth hormone levels, coincidentally, drop like a bitch (14% per decade, dunno if that's simple or compound interest).


GH is triggered/upregulated by growth hormone releasing hormone (GHRH). It is also thought to act mostly through the upregulation of IGF-1 (Insulin-like growth factor). (((Since mutations in IGF-1 receptors in mice lead to big life extension effects, and caloric restriction is also probably related to lowering IGF-1 levels, this seems like a big no-no))).


Early smallish experiments injecting GH into over 60 year olds increased muscle mass sometimes, by a little bit, decreased fat content and increased bone density. No cognitive benefits though, and raised blood glucose levels. The effect on muscle mass was also 10 times smaller than doing exercise.

Studies then tried raising GH by going upstream and injecting GHRH (((mainly because it's a simpler/cheaper molecule I think))), but while it triggered GH, they weren't seeing the increases in IGF-1 that they wanted, unless they injected twice a day. Also, IGF-1 trended back to pre-injection levels during the study.

Finally, some small synthetic molecule was found by accident to raise GH levels. It was modified so that it could be sniffed or eaten which is a big benefit over injections. It raises GH, raises IGF-1, doesn't do anything crazy.

(((Conclusion: no obvious data with regards to longevity. The samples were way too small and young to look for mortality differences. All studies here I think were on quite small groups (20 people or less). No obvious benefits with respect to immune system. If it does turn out to be beneficial, the synthetic seems like a nice thing to have. The author is much more upbeat than this though)))

Abstract follows:

During childhood and early adult life, growth hormone (GH), secreted by the anterior pituitary, is involved in the growth of bones and muscles and other organs as well. Aging is characterized by a decrease in muscle mass and bone strength and an increase in adipose, similar to the effects of pathological hyposecretion of GH in the young. Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level.

The GH hypothesis of aging posits that with the availability of human recombinant growth hormone and human recombinant insulin-like growth factor-I, which mediates most of the effects of GH, the GH hypothesis has become testable. Initial experiments involving short term administration of GH in a group of elderly men did indeed show modest improvement in lean body mass and adipose tissue. These studies are sometimes—and incorrectly—taken as proof of the correctness of the growth hormone hypothesis of aging. Subsequent year-long studies have shown GH therapy causes significant adverse effects. Other concerns of long-term treatment include possible diabetogenic effects, potential for increased risk of cancer, and high costs (>$10,000/yr). IGF-I, which mediates most of the effects of GH, is also being explored experimentally, but its role as a growth factor raises fears about tumor induction.

Methods being explored to raise GH levels more physiologically include: GHRH, the GH— releasing hormone produced by the hypothalamus; GH-releasing hexapeptides (GHRPs) which stimulate GH secretion via a novel receptor whose normal function is unknown; and orally active aromatic compounds, developed synthetically which mimic the effects of GHRPs. Because of the unknown long-term effects of elevated GH in the elderly, mimetics should be carefully restricted to clinical trials and temporary needs.