Can We Use Endogenous Growth Hormone Secretion Instead of Exogenous Growth Hormone Injection for Anti-Aging?

The provided text details the results of a 5-year “N-of-1” (single subject) self-experiment investigating the effects of a Growth Hormone Releasing Hormone (GHRH) gene therapy. Unlike exogenous Human Growth Hormone (hGH) injections, which flood the body with the hormone directly, GHRH is a precursor that signals the pituitary gland and other tissues to produce and release endogenous growth hormone.

The subject underwent two treatments of a plasmid DNA containing a 31-amino-acid GHRH sequence, administered into the thigh muscle via injection and electroporation one year apart. The gene expression was tied to a myosin promoter, meaning the GHRH was intended to be synthesized in response to muscle exercise and repair rather than continuously.

Objective Biomarker Changes

The experiment yielded several quantitative changes in the subject’s biological markers over the 5-year observation period:

  • GHRH Levels and Acromegaly Risk: The therapy successfully maintained elevated GHRH levels over 5 years, with a mean of 195 ng/mL after the second dose, compared to a normal human range of 7-15 ng/mL. Despite this massive increase in the precursor hormone, actual Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels remained well within normal ranges for the subject’s age. This suggests the body’s natural negative feedback loop successfully prevented the unchecked GH production that typically leads to acromegaly.
  • Testosterone: Total testosterone levels increased by approximately 52%, rising from a baseline of 484 pg/mL to a post-treatment mean of 671 pg/mL.
  • Cardiovascular and Metabolic Markers: The subject’s resting heart rate demonstrated a persistent decline of 8 to 13 beats per minute. The lipid profile also showed quantifiable improvements: the LDL to HDL cholesterol ratio dropped from 3.61 to a mean of 2.81, and triglycerides were reduced by more than half, dropping from 196 mg/dL to a mean of 94.4 mg/dL.
  • Immune System: Blood panels showed increases in immune cell counts, specifically a 20.2% mean increase in white blood cells, an 11.7% increase in CD4 cells, and a 12.0% increase in CD8 cells.
  • Biological Aging Clocks: At the chronological age of 64, the subject’s epigenetic age was tested at 58 years old (a 9.3% reduction). The Horvath PhenoAge calculation showed a 44.1% reduction post-treatment, while telomere age remained standard for his chronological age.
  • Vision: Clinical eye exams recorded a dramatic but temporary improvement in spherical vision correction shortly after the first dose, which slowly drifted back toward baseline over the subsequent 5 years.

Documented Adverse Events

While the author subjectively reported numerous positive feelings (like euphoria and faster healing), the clinical logs recorded several objective adverse physical events during the study period:

  • Severe (Grade 3) Events: The subject suffered a new L3/L4 lumbar disc protrusion, a partial tear of a muscle attachment in the shoulder, and the spontaneous detachment of an old collagen scar beneath the skin.
  • Moderate (Grade 2) Events: The subject experienced preventricular contractions (PVCs) during physical exertion, instances of polyuria/hyponatremia, and a dislocated shoulder “pop”.
  • Out of concern that high GHRH levels were negatively affecting senescent cells and causing soft-tissue weakness, the subject self-administered a course of senolytic drugs (dasatinib and quercetin) in 2019.

Considering that many may face paywalls or lack download permissions, I have uploaded the full manuscript here. Please share your insights. @DrFraser @KarlT @DeStrider @A_User
Results of a 5-Year N-of-1 Growth Hormone Releasing Hormone Gene Therapy Experiment.pdf (562.0 KB)

Search this site for tesamorelin, some are using it to mimic reproduce the triim study. Also, see the various studies on the effects of tesamorelin on the hiv population.

To me, one of the most important parts of the triim study is the level at which they sought to keep igf-1 levels, about 200 ng/mL, which in the population (people >65 ) corresponds to a zscore of around +2. In my opinion, how you get to that level is up to you.

This is how it is, unless you have tumors that makes you secrete extra growth hormone. The other way it happens is by abusing exogenous hgh (probably around >6iu daily ), but in this case the people doing the abuse are aware of this and many other risks of injecting supra levels of hgh.