One global way of stimulating senescent cells to re-enter the cell cycle is through GH (growth hormone) and IGF (insulin-like growth factor) pathways, giving the cell a chance to benefit from improved autophagy (cellular cleaning/ checks and balances) and mitophagy (mitochondrial checks and balances). Growth hormone-releasing peptides work in various ways to improve cell cycle functioning and proliferation to signal endogenous growth hormone. These hormones are also used to improve the landscape for improved DNA repair so the cell can confidently reenter the cell cycle.
The purpose of administering GHRPs is to elevate the physiologic release of endogenous GH, improve downstream transcription, and help with the translation of hepatic and more importantly extrahepatic cellular IGF1. Keep in mind that using GHRH (growth hormone-releasing hormone) by itself does not necessarily mean there will be an immediate endogenous growth hormone release. The machinery in the anterior pituitary secretagogue is set in motion to produce the pulse of growth hormone, but the hypothalamus still controls the release of GH, with somatostatin having a rate-limiting effect. In this way, though GH will be released once somatostatin inhibition is lifted. It’s for this reason that it’s important to consider using a GHRP in combination to ensure endogenous growth hormone release within a desired 20-minute window.
It’s important to understand how consumed nutritional substrates affect GHRH/GHRP peptides. Pure protein has no effect on the release of GH; on the other hand carbohydrates and fatty acid consumption can blunt the release of GH. Here is the rule: No food for up to 30 minutes after GHRH/GHRP use and no food 1 ½ hours prior to use. These are the only peptides known to be affected by nutrition.
GHRH is pleiotropic simply put this means it is producing more than one desired effect, which is why we use it in combination with many of our protocols/programs. It has been discovered that there are GH receptors found in most of the tissues of the body:
❖ Immune-beta cells/monocytes (not T cells)
When GHRH and GHRP are used effectively, they can upregulate endogenous GH and IGF to improve cell efficiency by:
❖ Upregulating beta-oxidation
❖ Upregulating oxidative phosphorylation
❖ Upregulating PGC-1alpha
❖ Upregulating PPAR-gamma
❖ Improving mitochondrial efficiency
❖ Upregulating the SIRT gene
❖ Activating the FOXO gene
❖ Improving the stem cell stress response and maintaining the quiescent state
❖ Decreasing cellular senescence
❖ Improving cellular autophagy
❖ Improving cellular mitophagy
❖ Decreasing cellular apoptosis
❖ Improving intracellular cortisol production
❖ Improving immune function with a decreased TH17/TReg ratio
❖ Improving NAD+/NADH ratio (increased)
❖ Improving NADP+/NADPH ratio (decreased)
Types of GHRH (growth hormone releasing hormone)
❖ Sermorelin: First GHRH FDA-approved for short stature
❖ MOD GRF (1-29) known in the industry as CJC 1295 without DAC (drug affinity complex- increases the half-life of the peptide)
❖ CJC 1295 (MOD GRF (1-29) with DAC)- this is the one that has the increased half-life
❖ Tesamorelin: Was FDA approved for visceral adiposity in HIV patients
Types of GHRP (AKA ghrelin mimicking peptide) (these are the two that we use; there are others.
❖ Ipamorelin: (most commonly used) the mildest of the GHRPs.
➢ Does not create prolactin or cortisol (this makes it safer)
➢ Gives a large release of GH without causing desensitization, even at very large doses
❖ MK677 (Ibutamoren) GHRP mimetic
➢ Strong GH and potential supraphysiologic IGF1 response