One of the ultimate frontiers of medical science is the victory over the process of aging. The ability to reduce physiological age vis-`-vis chronological age would enable people to not only prolong, but also improve the quality of their lives. A youthful physiology is characterized by an abundance of human growth hormone (GH), a marker that is shown to steadily decline with increasing age. Growth hormone therapy has consequently gained prominence as a therapeutic measure to control the aging process. However, GH is known to undergo hepatic conversion into the mitogen, type 1 insulin-like growth factor (IGF-1) (see Figure 1). Mounting evidence , indicates that in the early stages of cancer, higher levels of circulating serum IGF-1 are present, either through its enhanced production or via the downregulation of the IGF-1 receptor. This implies that artificially raising GH levels in the body should be viewed with caution.
How can growth hormone therapy be safely applied to anti-aging strategies? The answer to this question lies in properly understanding the mechanism that controls the growth hormone concentrations in the serum: the hypothalamic-pituitary axis (HPA) (Figure 1). The hypothalamus produces two key substances, somatostatin and growth hormone releasing hormone (GHRH). Acting on the pituitary, somatostatin inhibits and GHRH stimulates the release of endogenous growth hormone. With that knowledge, it is logically possible to control growth hormone levels in the body by either (a) exogenous administration of artificially prepared growth hormone, or (b) tweaking the inhibitory or stimulatory effector system of the HPA.
One of the challenges faced by exogenous GH therapy is the natural body regulatory mechanism that counteracts increasing GH levels through an inhibitory feedback loop. The balance shifts from stimulation with GHRH to inhibition by somatostatin, thereby creating a potentially chronic inhibitory state over time, dangerously depleting natural GH reserves in the pituitary.
It is conceivable that stimulation of the HPA towards maximizing its production of endogenous GH may be a much better and safer alternative than exogenous administration. This strategy would be expected to have the following advantages over conventional GH therapy:
- Optimization of the endogenous GH levels within the physiological limits of the system;
- Improvement of GH stores in the pituitary for continued release;
- Minimization of the negative feedback loop by providing a source of pituitary stimulation;
- No undesired stimulation of potentially harmful levels of IGF-1, as has been reported for recombinant GH therapy.
Figure 1. The Hypothalamic-Pituitary Axis: The regulation of endo-genous growth hormone
In practice, this form of GH therapy is achieved through the administration of GHRH analogs. Currently, only two clinically validated GHRH analogs are commercially available. The first one is Geref, a 22 amino acid analog of GHRH, produced by Serono Labs in Nowell, MA.
The second GHRH analog is Vitalife. Vitalife is a polypeptide combinant, consisting of four different naturally conjugated amino acid sequences that are not recombinant in nature. Vitalife is produced by a European company called Balance Dermaceuticals. Unlike Geref which is administered via subcutaneous injection, Vitalife has the distinct advantage of being administered non-invasively through transdermal delivery.
Clinical trials described here have shed light on the remarkable properties of Vitalife. In a nutshell, Vitalife treatment clearly exceeds the expectations of the idealized GH therapy by increasing endogenous GH levels without stimulating the inhibitory feedback loop, and by actually suppressing the production of IGF-1.
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