Here presented for the first time are results showing persistence over a 5+ year period in a human [Brian P. Hanley] who had a hormone gene therapy administered to muscle.

This growth hormone releasing hormone (aka somatocrinin/somatoliberin/GHRH) therapy was administered in 2 doses, a year apart, with a mean after the second dose of 195 ng/mL (13 × normal, σ = 143, σ_M = 34, max = 495, min = 53). This level of GHRH therapy appears to be safe for the subject, although there were some adverse events.

Heart rate declined 8 to 13 bpm, persistent over 5 years. Testosterone rose by 52% (σ = 22%, σ_M = 6%). The high-density lipoprotein/low-density lipoprotein ratio dropped from 3.61 to mean 2.81 (σ = 0.26, σ_M = 0.057, max = 3.3, min = 2.5), and triglycerides declined from 196 mg/dL to mean 94.4 mg/dL (σ = 21.9, σ_M = 5.0, min = 59, max = 133, min = 59). White blood cell counts increased, however, the baseline was not strong: CD4 and CD8 mean increased by 11.7% (σ = 11.6%, σ_M = 3.3%, max = 30.7%, min = −9.6%) and 12.0% (σ = 10.5%, σ_M = 3.0%, max = 29.1%, min = −6.7%), respectively. Ancillary observations comprise an early period of euphoria, and a dramatic improvement in visual correction after the first dose, spherical correction from baseline (L/R) −2.25/−2.75 to −0.25/−0.5. Over the next 5 years, correction drifted back to −1.25/−1.75. Horvath PhenoAge epigenetic clock was cut 44.1% post-treatment. At completion, epigenetic age was −6 years (−9.3%), and telomere age was +7 months (+0.9%).

[Keywords: GHRH, GRF, GHRF, growth hormone releasing hormone, somatocrinin, somatoliberin, somatorelin, self-experimentation, n-of-1]

…Sans anesthetic, electroporation elicited the remark, “On a POW that would be a war crime.” Available literature greatly understated sensations.

Euphoria: The subject reported being euphoric after the first inoculation, a feeling of “more intense reality” with joyful/blissful body feelings. One adviser to the study was quite concerned, being of the opinion that euphoria was probably signaling pathology, and so, it was logged as a mild grade 1 adverse event. The subject did not think it was pathological, nor adverse.

A self-experiment provides for more than an objective observation of the experiment. The subjective experience can also inform us, allowing observations that could be missed. This experiment generated a number of such, and a third person will be dispensed with for this section.

The first inoculation was traumatic, causing strong activation of the quadriceps, and an electrical shock sensation. Inoculation sites on both legs felt “hit with a hammer.” Modifications made the second inoculation go smoothly. This is ascribed to 2 things. Without tetany of muscle cells near the electroporation site, there was no trauma to the muscle from that cause. Also, chilling prevented tissue heating.

I was surprised (because I believed that this dose would be too low to be perceptible) that in the first half-hour, I felt a tingling sensation that I had never experienced. I speculate that this was due to rapid stimulation of gonadotropin release, and the rise in testosterone level fits this idea. The first inoculations were primarily intended as a live test of the protocol. Low dose was serendipitous, as I well may have canceled the experiment and removed the site if the euphoria had continued to increase.

Over the first several days I felt better and better—my legs and whole body felt lively when going cycling, and I wondered if this could plausibly be a placebo effect. This liveliness then went over the edge into euphoria that was so strong I did not care enough to bother putting my foot down as I fell over on my bicycle due to moving too slowly. I think this suggests that GHRH, through receptors in the central nervous system, has an upregulating effect on a range of neurotransmitter receptors in the receptorome.

A curious effect on muscles occurred in the first week that I suspect is connected to later developments. During arm weight work, a sensation occurred as if minuscule spots at or near the attachments of upper body muscles were popping. This slight stinging sensation was so distributed, and so tiny for each of the countless locations, that it didn’t bother me enough to stop. Later, I had old soft tissue injuries recur, a second lumbar disc herniation, then a new shoulder injury. This shoulder injury occurred on a relatively light body weight rep after a maximal weight effort competing with young men in their mid-20s. The injury was not a full tear.

However, there was an unusual event that suggests something more. I had a motorcycle accident at 18, which left me with a gouge in my right kneecap and a lump of collagen/scar ~0.6 cm thick × 1 cm × 2.5 cm. This lump spontaneously came loose and slipped down under my skin. It was absorbed in a 3-week period.

The first hypothesis about these injuries is that higher exercise tolerance drove my body beyond its current limits. The second hypothesis is based on speculating what saturation levels of this hormone might do to a senescent cell. It may be that senescent cells respond and create weaker tissue, or undergo apoptosis in doing so. A third hypothesis is that there may be an expression level of GHRH that corresponds to childhood, perhaps very young childhood, and triggers some neotenous cell growth pattern.

Because of concerns about further soft tissue effects, in July 2019, I decided on a course of senolytics (dasatinib 400mg and quercetin 4g per day for 5 days) repeated 2 months later. Since then, there have been no new events. A cycling crash (over 20MPH) shortly after the second course of senolytics resulted in a mild concussion, and no other injuries, despite hitting so hard, that immediately afterward I was sure I had multiple broken bones. I have had cycling accidents in the past, breaking both wrists, a collarbone, etc. This crash was like having an accident in my 20s. As I sprinted to avoid a speeding car, I put too much focus on the car that stopped half-way across the intersection with squealing tires, and caught a pedal on the pillar in the middle of the bike path entrance.

The mental effects were pleasant after the first inoculation and largely so after the second. However, the second inoculation also included disturbing effects. My physiological responses to the world around me changed completely. This isn’t a mental thing, it’s in the body, what the Japanese call the hara. It became apparent that my identity foundation is integral with this. I talked with a psychiatrist, and did meditative exercises intentionally embracing and accepting who I was now. This was difficult, including what most would call nightmares. My unconscious operated like a child’s, piecing metaphors together to understand what I had done. I didn’t feel afraid, I felt unmoored, wondering why I felt no fear. This was probably a dose effect.

An effect I didn’t expect and still remains is that I feel I felt rejuvenated after doing leg work. This isn’t a minor effect. I consistently go in tired and by the end of my workout feel like doing it again. This begins to dissipate 2–3 hours later, and I suspect it is a direct effect of GHRH production triggered by use of the affected muscles. This also signals that upregulation of the myosin gene happens within 20–30 minutes of heavy exercise stimulation.

Sleep improved dramatically, becoming like a teen’s sleep for a couple of months after first inoculation. This faded, in part, probably from stress, but overall sleep improved. Since 2 months after second inoculation I wake up so hungry I cannot sleep. Eating a sizeable (800–1,000 calories) meal before bed can sometimes get me through 6 hours. However, I should note that my normal exercise schedule is 6–7 days a week, 1–2.5 hours per weekday session and up to 5 hours on weekends.

The GHRH graph shows impressive expression for more than 5 years, the first finding of such long-term expression. After 5.5 years, this level of long-term expression does appear to be reasonably safe.

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