Speculations about the mechanism do not make the demonstrable life-extendig effect of downmodulating GH signaling go away.
Despite what we see in mice, humans with pituitary dwarfism do not show an extended lifespan or any reductions in age related pathology. Before you cite references on the infamous "little people of Krk", a geographically isolated population who as a consequence of interbreeding tend to carry numerous hereditary diseases including dwarfism, albinism, paralytic spasticity, cataracts and mental retardation, bear in mind that the longest lived Krk individual recorded was 91 years old - hardly extraordinary. Human dwarfism resulting from hypopitutiarism is associated with numerous endocrine complications that will contribute to decreasing lifespan.
If you have any evidence that lowered GH levels contribute to lifespan in humans let me know - similarly if you have any evidence that raising age related GH deficiency to more youthful levels contributes to any pathology.
Lely (1) writes, "it might even be dangerous to use excessive GH dosages in conditions in which the body has just decided to decrease GH actions". Firstly we are not talking about excessive but youthful levels and secondly, since when has medicine been at the mercy of the body's decisions?
Supposing we are able to increase neurotrasmitter function in the brain or immune function to youthful levels should we not do this because the body has "decided" to enter into an aging program that decreases these functions? Of course not - it would be absurd. Yet this is instrinsically the myopic rationale which is being promulgated.
Do we resign the cancer patient to death when he is diagnosed? No - we intervene by surgery, chemotherapy, radiotherapy and any other treatment available including experimental ones when the patient becomes terminal. Why should we not act similarly when it comes to aging?
Aging is at present an incurable disease. But it is a disease. We should not have to wait until the clinical manifestations of aging become gross to seek, at the very least, symptomatic relief. The inexorable processes of aging set in far sooner than the appearance of significant physical manifestations which makes the need for a procative rather than reactive interventional approach even more important.
Growth hormone is associated with substantial adverse effects. In a clinical trial of healthy women (n = 57) and men (n = 74) aged 65 to 88 years, GH administered subcutaneously at an initial dose of 30 µg/kg, 3 times per week, then reduced to 20 µg/kg, was associated with carpal tunnel syndrome in 38% of women vs 7% of those taking placebo, and in 24% of men vs 0% taking placebo; edema in 39% of women (0% for placebo) and 30% of men (12% for placebo); and arthralgias in 46% of women (7% for placebo) and 41% of men (0% for placebo). Eighteen men treated with GH developed glucose intolerance or diabetes compared with 7 men in the nontreatment group.
Olshanky's article (2), without suitable qualification to show that GH supplementation has serious side effects (many commonly prescribed anti-inflammatory agents have far more serious side effects than those cited above) is a grave loss for many patients who otherwise would have had the opportunity to be treated with GH. Considering the impact that such an article would have on an already lawsuit-fearful medical community I wonder if he fully recognises and is willing to take responsibility for the many patients who are going to miss out as a result of this dubious article.
Given the clinical concerns and the legal issues involved, we believe that physicians or other persons who currently market, distribute, or administer GH to their patients for any reason other than the well-defined approved (ie, legal) uses of the drug, should not do so.
Rubbish. Thankfully, the reason for GH administration remains the prerogative of the medical practitioner.
(1) Justified and unjustified use of growth hormone
A J van der Lely
Postgraduate Medical Journal 2004;80:577-580
(2) Provision or Distribution of Growth Hormone for "Antiaging"
Thomas T. Perls, MD, MPH; Neal R. Reisman, MD, JD; S. Jay Olshansky, PhD
JAMA. 2005;294:2086-2090