Epithalon (also known as Epitalon) is the peptide AEDG

AEDG peptides in concentrations 0.05-2.00 ng/ml on organotypic skin cell cultures proliferation in young and old animals were investigated. Peptides stimulated skin fibroblasts proliferation on 29-45% in skin cell cultures of young and old rats.
https://www.ncbi.nlm.nih.gov/pubmed/25946846

[The influence of substances revealing geroprotective of spontaneous carcinogenesis in mice].
[Article in Russian]
Popovich IG.
Abstract
The review presents the results of experimental studies conducted by the author. CBA, SHR, HER-2/neu and SAM mice revealed inhibition of age-related alterations in estrus function and spontaneous tumour development and showed life span extension under
the influence of the pineal gland hormone Melatonin, synthetic peptide bioregulator Epitalon, delta-sleep-inducing peptide Deltaran, enterosorbent Aqualen and succinic acid containing preparation Neuronol (Noogam). The observed effect depended on the
dose and conditions of administration, as well as genetic predisposition of the particular mice strains to tumour development.
https://www.ncbi.nlm.nih.gov/pubmed/15559508

Wikipedia says:
A human prospective cohort study conducted on a sample of 266 people over age 60 demonstrated that treatment with epithalamin, the pineal gland extract upon which Epitalon is based, produced a 1.6-1.8-fold reduction in mortality during the following 6
years, a 2.5-fold reduction in mortality when combined with thymulin, and a 4.1-fold reduction in mortality when combined with thymulin and administered annually instead of only once at study onset

also:”following 3 years of biannual epithalamin treatments, as well as a 50% lower rate of cardiovascular mortality, a 50% lower rate of cardiovascular failure and serious respiratory disease, and a 28% lower rate of overall mortality” https://en.
wikipedia.org/wiki/Epitalon

I perceive that I read AEDG (epithalon) makes laboratory rodents live about 24% longer, during 2019 I found:
Epithalon (0.1 microg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the
maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively.
https://www.ncbi.nlm.nih.gov/pubmed/18856211

If a rat lives about 2.5 years, then the 137 day number is about 6.6 ish % longer lifespan

Mammal studies are better, but at drosophila:
The geroprotector activity of epitalon, a synthetic tetrapeptide Ala-Glu-Asp-Gly, was studied on the Drosophila melanogaster wild strain Canton-S. The substance was added to the culture medium only at the developmental stage (from egg to larva).Epitalon
significantly increased the lifespan (LS) of imagoes by 11-16% when applied at unprecedented low concentrations-from 0.001 x 10(-6) to 5 x 10(-6) wt.% of culture medium for males and from 0.01 x 10(-6) to 0.1 x 10(-6) wt.% of culture medium for females.
The increase in LS did not depend on the substance dose. Effective concentrations of epitalon were 16,000-80,000,000 times lower than those of melatonin.
https://www.ncbi.nlm.nih.gov/pubmed/11087911

The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a
possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase.
https://www.ncbi.nlm.nih.gov/pubmed/15990728

Longevity technology:
• The peptide AEDG is published as causing greater longevity and wellness in laboratory mammals, making a version of AEDG with weekly, monthly, annual or multi-annual dosing is beneficial.
• Fluoexetine palmitate is once weekly dosing; AEDG palmitate could be weekly dosing
• “Paliperidone Palmitate 3-month injection” suggests 3 month injection could function 3 months, noting the few nanograms or few milligrams of AEDG it is possible to think an AEDG palmitate could last longer than three months. “Six-month depot
formulation of leuprorelin acetate” suggests 6 month AEDG dosing could be functional.
• The needleless injection technology that is like transdermal sugar dermal piercers could work at the nanograms to milligrams of AEDG to provide beneficial effect. “AEDG peptides in concentrations 0.05-2.00 ng/ml on organotypic skin cell cultures
proliferation in young and old animals were investigated. Peptides stimulated skin fibroblasts proliferation on 29-45% in skin cell cultures of young and old rats.” (PMID:25946846) suggests a therepeutic effect over a range of 1 to several hundred
units of dosage having beneficial effect, that gives the possibility of the beneficial human drug being active at even transdermal needleless injection.
• The dosing amount of epithalon, AEDG might be larger than the mg dosages described at other items here. “Injectable Epithalon use (most effective): duration: 10 - 20 days dosage: between 5 - 10 mg per day”, also, “Each 10 - 20 days course of
Epithalamin is followed by 4-6 months pause before repeating” (http://steroid.es/epitalon.html) suggests that 100-200 mg depot injection annually could be beneficial. Supporting nanogram to single milligram 6 month or longer depot dosages is, “In
vitro biotesting included the determination of the proliferative activity of thymocytes, a bimodal curve with the second maximum were detected at super-low doses (10(-17)-10(-15) mol/l). Authors propose a hypothesis that for superlow concentrations the
formation and distance transmission of a signal from ligand to a target cell without the formation of any ligand-receptor complex take place.” (PMID:12881997)
• AEDG is orally active in rodents, it is possible AEDG toothpaste could beneficially dose humans.
• Some proteins glom to circulating albumins like SHBG strongly, it is possible that attaching AEDG to one of those proteins with a very gradually dissolving enzymatically dividable linker could cause 1 to 3 month or greater AEDG dosing intervals and
be orally administered. Oral dosing: salmon calcitonin linked peptides pass through the GI tract for oral delivery of peptides.
• I may or may not have read about injectable chemical ID, if that is non-isotopic then AEDG linked to that chemical could have annual or multiyear dosing.
• Putting an atom or a few on the AEDG peptide, like changing the =O to -OH at few places, or changing hydrophilicity or lipophilicity could make nanogram dosing possible from modifying the distance between AEDG and a cytostructure or external
cytomembrane structure, rather than the activation of a receptor with AEDG, “In vitro biotesting included the determination of the proliferative activity of thymocytes, a bimodal curve with the second maximum were detected at super-low doses (10(-17)-
10(-15) mol/l). Authors propose a hypothesis that for superlow concentrations the formation and distance transmission of a signal from ligand to a target cell without the formation of any ligand-receptor complex take place.” (PMID:12881997)
• Variations on AEDG that do the “to a target cell without the formation of any ligand-receptor complex” thing at nanogram dosages: deuterated AEDG could have slightly different intramolecular distances; blood brain barrier passing version of AEDG
like diacetylAEDG (possibly with enzyme degradable linker molecule),
• • Lysine-EDG (LK) is similar to AEDG, and has both similar and different effects.
• There are over 100 mentions of epithalon, AEDG at pubmed, epithalon is a pineal peptide, there are numerous other pineal peptides that could be beneficial to humans, “Within the epiphysis polypeptide complex, free amino acids (3.26%), dipeptides (
23.19%), tripeptides (50.72%), tetrapeptides (22.10%), and pentapeptides (0.72%)” The thing is though, “The biological effects of the epiphysis polypeptide complex are determined by the effect of its component AEDG”
• • The peptide KED (Lys-Glu-Asp) is about 40% more effective at, “The effect of AED (Ala-Glu-Asp), KED (Lys-Glu-Asp), KE (Lys-Glu), AEDG (Ala-Glu-Asp-Gly) peptides and their compound on neuronal differentiation of human periodontal ligament stem
cells (hPDLSCs) was studied by immunofluorescence and western blot analysis.” also: “Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis”
• There is also a nonapeptide, thymulin, wikipedia says, “Thymulin” “is a nonapeptide produced by two distinct epithelial populations in the thymus” “It requires zinc for biological activity. Its peptide sequence is H-Pyr-Ala-Lys-Ser-Gln-Gly-
Gly-Ser-Asn-OH.”
• “acetylated and acetyl-amidated versions” of AEDG are described, that reminds me of acetylation to cross the blood brain barrier and possibly other cytomembranes: https://www.reddit.com/r/Nootropics/comments/3ji7d8/epitalon_any_noticeable_results/
• Also, attaching AEDG to a protein with favorable cytomembrane transport channels, likely with an enzymatically degradeable linker molecule or ATP or polyATP could cause the AEDG beneficial effects at lower doses making annual or multiyear dosing more
effective.
• nuclear membrane transport channels: Also, noting “cause the recognition and complementary binding of a regulatory peptide with DNA functional groups” It is possible a material that causes AEDG to be preferentially transported to the nucleus
through the nuclear membrane could increase the activity of AEDG at any particular dose, making annual or multiyear dosing even more effective.
• noting, “The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding
model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase.” It is possible there are different
genotypes for the ATTTTC sequence and that persons with variations can be measured as to wellness and longevity to find an optimal version of the sequence. The more optimal sequence could then be made part of the human genome. AEDG could also be
produced at human, that is persons, that is people’s tissue with gene therapy.
• Mammal and human studies could find out if AEDG which effects melatonin production benefits the fetus and baby as much as melatonin is published as benefitting fetuses and babies, This study notes higher fertility when conceiving and greater
resistance to trouble at the new baby, “Melatonin receptors are widespread in the embryo and fetus since early stages. There is solid evidence that melatonin is neuroprotective and has a positive effect on the outcome of the compromised pregnancies.”
The journal article also says, “The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal melatonin provided transplacentally. Melatonin appears to be involved in the normal outcome of pregnancy
beginning with the oocyte quality and finishing with the parturition” Also, “Melatonin decreases in conditions associated with serious outcome for the fetus and seems to be involved in preeclampsia and intrauterine growth restriction [7]. Melatonin
treatment during human normal or abnormal pregnancy has been studied for a large range of conditions and at different times during the gestational period. Considering the ethical issues, it is more difficult to study a normally occurring pregnancy, than
an in vitro fertilization (IVF) one. Melatonin administration started prior to IVF-cycles, continued during pregnancy and was associated with improved pregnancy outcomes”, also, at in vitro fertilization, “Fertilization success and pregnancy rate
were improved by melatonin treatment. Fertilization rate was 50% higher in melatonin treatment cycle“ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316124/
•
• • AEDG, epithalon is on alibaba.
•
• GSK Drug delivery technology if surgical glue is painted on a body surface does it do transdermal drug delivery with a one time monthlong or longer lasting swab which is more advantageous than other transdermal methods. Foot area or buttock cleft or
acute angle area of knee could be possible sites, with the knee angle administerable easily by the user. It might be fine on clean skin, but a thioglycollate (keratin dissolving) or microdermabrasion moist pad might be a beneficial surface prep.
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