GSK:

[Treon Verdery]

Also there is the possibility that the duration of an atopic dermatitis treatment could work chronologically longer, my perception is that a halogenated cortisone ointment kind of does things when it is is gooey and on, then sort of rubs off onto other things, then might not be doing that much 11-14 hours after application; I think I read that fluorocorticoids are 1000 times more physiologically potent than nonhalogenated cortisone so that brings up the possibility that compared with 100% strength at 1 minute, and 1% strength at 720 minutes there might be a way to cause fluorocorticoids that treat atopic dermatitis to linger and even fluidicly recycle so they are are 100% at 1 minute but at like 40% at 720 minutes; one possibility is actually exterior of cell cytotransport to cytoplasm facilitating molecules, and also cytoexport (efflux) molecules (possibly peptides) being attached to the fluorocorticoid molecule, this would cause a kind of chemical engineering, it pours into the cell cytoplasm at a certain amount/minute and it pours out of the cell at a certain amount per minute, whle being right next to the cell and all the cytoexterior fluorocorticoid receptors, so the amount outside the cell, while near the cell exterior receptors is at a particular moderate to high range with a long plateau curve; I perceive that topical halogenated corticosteroids might actually work on receptors on the exterior of cells to get rid of atopic dermatitis, so there could even halogenated corticosteroids that had some kind of intracyte space area physiological tropism, although Ido not know how that works, perhaps one of thephysiologicially beneficial interleukins that I mighthave read accumulate at the inter cyte could be attached to the halogenated corticosteroid molecule, even though the beneficial interleukin is many AMU and the halogenated corticosteroid is few AMU



Then there is the possibilityof a new atopic dermatitis drug: is there anything, which if actually actively transported to the cytoplasm, completely a different place than the receptors on the cells exterior, that would decrease atopic dermatitis physiochemistry and symptoms, like perhaps something that, at the cytoplasm, makes capillary epithelial cytes exude less fluid (plasma), or causes dermatocytes to exude less fluid; (my perception during the 20th century AD was that moisture->itchiness) or I read about some kind of tolerancization of immunoresponse thing having to do with non-mature dendric immune cells, as well as beneficial inteleukins, so perhaps there could be some RNA or DNA drug that causes the person’s own genome to make something that the tolerance promoting young dendric cells respond to with decreased immunoreactivity around dermis (skin), another possibility besides RNA (mRNA) as well as DNA drugs at topical liposomal or nanoemulsions are things with a nuclear membrane transport peptide attached to them, imaginably this could cause 7-40-100 times more movement of the nucleus effecting drug to actually reach the nucleus (like DNA drug);



Also, I read about things like HDACinhibitors, and methylators, perhaps theycould findout ifthere is any kind of histone modification, like preserving acetylation, or demethylating some part of the histones, that causes people to have less atopic dermatitis; there are numerous orally active histone deacetylators, and some like 10HDA (also possibly 10H2DA and 90DA), that occur at natural products that cause greater longevity at mice, and one called Vortsomething also called SAHA that causes greater cognitive ability; so there could be a histone acessibility and activateability drug, thatis oral, that causes a personto be absent having atopic dermatitis thatmakes them live longer or also be more intelligent;



People that value atopic dermatitis being cured could do gene therapy, I think the topical availabillity, the ability to dothings like electroporation, andhere is a thought new to me, the ability to, using the same genome, turn the genes at the dermis on and off so they are like those at a cell that has differentiation, could make it so thatturning off some of the genes at the dermis, or turning some on, might make the persons skin as nonresponsive to atopic dermatitis causes as the least immunoreactive cell type at the rest of their body; Perhaps like, the bloodbrain barrier is almost always completely immunononreactive, because it is important, so some kind of electroporation transported RNA or DNA drug that causes the active and available genes of the dermis to be more like those of the bloodbrain barrier would cause a gene and gene product availability/producibility to be like thatof the persons own blook brain barrier and their skin would be immune system unreactive; It seems possible they could also just find well normal people at the 99th percentile of having skin (dermis) that was spontaneously non-irritable and 99th percentile of nondeveloping of any kind of dermatitis even when a dermal chemical irritant was applied, who also had skin other people described as attractive and healthy, and then find out if the 99th percentile of nonirritability and nondermatis response had a particular group ofgenes that were nonavailable or less available for translation and transcription, and then make RNA and DNA topical drugs, or just possibly, if it lasts quite a while, an electroporation of gene expression modifying drug like RNA drug or DNA drug that causes the DNA transcriptiongenetics available to the persons dermis to belike the 99th percentile of people with irritationless, nondermatitis responsive skin; There is also the possibility that rather than Not Making things in response to an irritant, that 99th percentile of absence of skin (dermis) irritability and 99th percentile of absence of a dermatitis response even if there is a chemical irritant, among people that others quantify as having skinthat is moreattractive than the 90th percentile, is linked to the people with 99th perentile well dermis (skin) making something, that is expressing a gene and making a transcribed protein, that people with atopic dermatitis do not make as much of, that could then be addressed with topical RNA (mRNA) or DNA drugs, or possibly electroporation that cause those genes at a personwith atopic dermatitis to be more active, so they make the same amount of beneficial material as the 99th percentile of dermal wellness persons and then they ceasehaving dermatitis; Notably, if mRNA could function this way as a drug, and liposomes and nanoemulsions could bring the mRNA to the dermal layers that are alive, noting that thisis like micrograms, or possibly even nanograms of mRNA, it could be highly affordable being made out of ultrasonicated oil,phospholipids, water, and like .1 or .01 mg of mRNA per big jarful





At C elegans royalactin protein without 10HDA (10H2DA) has a longevizing effect, I perceive this was kind of near 1/3 the distance on the graph that the 10HDA (10H2DA) produced at c elegansas to increased longevity, so the 10HDA (10H2DA) was like three times more longevising than the royalactin; they could do a thing where they noticed the amount of activation at genes in C elegans, mice, and humans, when eating enteric coated (stomach passing) royalactin, to find out if any of the genetic changes that occur at C elegans that cause greater longevity from just royalactin also occur at mice and humans; also the mice eating the enteric coated royalactin could be dosed their entire lives and quantified to find out how much longer they lived, if anything different than 10HDA(10H2DA) amount of longevity increase, published at mice as 25/27% greater longevity from oral royal jelly; if the mice live longer from enteric coated royalactin, and their genes with different activation amounts have similar changes to activation amounts at human genes among human volunteers that eat enteric coated royalactin protein then it could be that royalactin, enteric coated or enteric optimized, is likely to cause greater human longevity; this brings up the possibility of engineering a protein with much higher longevity increasing effects than royalactin, at bees, yeast, or bacteria, the royalactin protein producing gene could be modified to produce different proteins, and then those proteins screened as a library at c elegans in 96 well culture plates to find out if any of the royalactin protein variants was more effective at increasing longevity; among numerous possibilities are lipophilic as well as hydrophilic varieties of royalactin protein; a version of royalactin’s protein bunch layer exterior, but with notably different number of atoms, that is fewer AMU, which could actually reach more tissues, more effectively as the atomic weight is less and it might have much more transport and diffusion; versions of royalactin protein where if you think of protein as a bunched up blob, then the amino acid sequence of the protein at just the royalactin exterior could be multiply repeated, with the technology that this would be kind of like a bunch of identical repeating space filling units of royalactin exterior; similarly dimerized (two royalactins) as well as trimerized (three royalactins) could be quantified as to longevity effect; also the nonsurface core of the royalactin protein could be quantified as to increased longevity effects, dimerized and trimerized as well; noting that similar gene activation patterns between c elegans, mice and humans as a response to royalactin may exist, quantifying the effects of royalactin protein modifications and variations could be accomplished at c elegans as welkl as mice tobenefit humans; noting that at c elegans royalactin was sort of 1/3 the longevity strength of 10HDA, and that entire material royal jelly is published as causing 25/27% greater longevity at mice, it is is possible that a new version of the royalactin protein that is three times as effective as the royalactin in royal jelly could possibly exist or be produced, and that this would be a new longevity chemical, supplemnet or drug to have the same amount of longevising effect as the 10HDA (10H2DA);

also, varieties of the royalactin protein that are the actual versions of the protein at the queen bee’s GI tract after the digestive area of the queen bee’s stomach could represent that actual protein forms that contribute to 20-40 times greater longevity at the queen bee than other bees, so that is another protein variation to quantify the longevity effects of, similarly, noting the 25/27% greater longevity at mice orally eating royal jelly, and the possibility that compared with a human stomach digestion duration of .5-3/4 of an hour that a mouse stomach digestion period is imaginably 5-7 minutes, it is possible that at mice, the royalactin protein is modified to a fewer AMU protein, yet still a protein, compared to royalactin possibly being digested into individual amino acids at a human; if royalactin is not fully digested at mice, then that modified fewer AMU royalactin protein product from the briefer mouse digestion is another possible longevity protein variant on royalactin to quantify the effects of; encouragingly, it is my perception that the luminosity and number of wavelengths of engineered proteins like green fluorescent protein have been amplified to many times the first protein’s luminosity, and more than 9 new spectral emissions wavelengths have been produced, it seems possible that tripling the longevity effect of royalactin protein at mammals could be possible; putting the genetics of a much greater longevity producing variant of the royalactin protein at plant food products and also possibly eggs at chickens that produce eggs, creates new longevity foods; Gene therapy so that people produce longevity proteins at their bodies, as well as germline gene therapy so that people produce longevity, wellness, and healthspan producing proteins at their bodies is also beneficial;



Online it mentions that royalctin causes activation of particular receptors, I read there is a gene expression measurment chip that covers the entire human genome along with another 6500 genes, and it is likely that that amount of capability is also available at the mouse genome, and possibly the c. elegans genome: the effect of royalactin on a very large number of receptors might be generated, and then the new different versions of royalactin and their amplitude of effect on these receptors could be quantified to produce new variants of the royalactin protein that have greater receptor activity; it is possible that the receptors that cause greater longevity at c elegans from royalactin could be qualified and quantified, and that, if mice are longevized with enteric coated royalactin, that the longevizing receptors that are quantifiably stimulated at longevized mice that also have human receptor equivalents could be researched as a basis for completely new non-protein longevity heightening drugs



It is possible that having e coli or yeast, of some species, (pichia pastoris has been utilized to make royalactin at a laboratory, during research on a possible basis for manufacturing production) process something like the amyl, propyl, butyl, hexyl,heptl, octyl acetates of GRAS food flavorings could cause some versions of variously esterified alkanes with perhaps one nonsaturated C=C link to be produced, and that this could be characterized and quantified as to longevity effects at mice, also, it is possible that 10HDA and 10H2DA are possible products, then this yeast modified GRAS material could be concentrated and distributed while being hundreds or thousands of times more affordable than royal jelly; imaginably the yeast could chemically transform plant based decanoic acids to partially saturated (C=C) decanoic acid esters (=O), online it says that decanoic acid, without a desaturated C=C, is at palm oil, coconut oil, and milk lipids, so there could be highly affordable sources of the C10 molecule for a desaturating C=C producing esterifying organism, possibly a yeast, to make into a quantitatively longevity increasing, at mammals, like mice, molecule that people could take as a supplement or drug hundreds or thousands of times more affordably than royal jelly, and at longevity heightening research supported tens, hundreds, or even thousands of times higher doses than royal jelly



One of the other royal jelly proteins could be quantified as to any nootropic effects it has on humans, “MRJP1 is also related to the learning ability of bees.” so an enteric coated nootropic protein active at humans could be possible



So, there is already a one pill, one dose yeast infection cure pill, fluconazole, is there a possible version that could be distributed and voluntarily used globally that is less than 1 cent a dose, and as a side effect makes people live longer? Fluconozole is $200/Kg, the one dose yeast infection amount is 150 mg, which is three cents per pill for the drug; Halogenation, ethynylization, also attaching the moiety that causes active transport (1000 times greater transport than diffusion) at the largest possible number of cytotypes and tissues could all be ways; 100 times more affordable from halogenation heightened effect per mg dose, and 40 times more affordable from ethynylization heighteing of effective mg dose, causes 4000 times more affordable pill; is 1/4000 of 3 cents, or less than 1/1000 of 1 cent per dose; globally as a medication printed on edible round paper, noting 396 adhesive applique papers that look festive are $1.00 retail at the dollar store; then it goes up to about 1/4 of 1 cent a dose; Placing folate at fluconozole to reduce birth defects: minute effects could have value at public well being; it is possible that over 50% of women globally conceive their first child between 18 and 28, that suggests that a folate plamitate that lasts 7 days could reduce birth defects in 1/120th/4 of per decade pregnancies if a woman takes it as part of curing one yeast infection per decade with a one pill yeast infection curing treatment; 400 mcg times 30 is 12 milligrams of folate per pill, or perhaps 24 milligrams of folic acid palmitate; at $30/Kg folate that is is 41,000 doses per $30.00 or 1/11 of 1 cent per dose to put as another chemical at a yeast infection curing one pill one dose paper form or tablet; I perceive that online 1/52 times 70% of 300,000 annual birth defects are preventable with folate, so 4038 annually or 40,380 per decade; at the likeliness of the week the yeast infection curing pill being the week a woman gets pregnant, then that is 40,380 birth defects prevented per decade when folate palmite is combined with a one dose yeast infection curing pill, for an entire pill $ at 1/4 of one cent at a retail US paper adhesive on paper dosage form;

Endogenous chemicals are found at some organisims that when given to other organisms cause the other organsisms to live longer; 10HDA, as well as 10H2DA are decanoic acids esters found in royal jelly, when royal jelly was fed to mice it caused the mice tpo live 25/27% longer, when other decanoic acid esters like DAEE were administered to mice their wellness and healing ability improved as did their resistance to cognitive stress, 90DA is another esterified alkane (with one C=C) with HDACinhibitor effects; Finding and screening a variety of ester (=O, the 10H2A and 10HDA also have -OH) 10 carbon atom molecules to find those that cause longevity effects, optimally longer than those of 10HDA nd 10H2DA could come from making tissue concentrates from the tissue of long lived species like: bowhead whales (multicentury lifespan), 400 year lifespan Quahog clams, 300 year lifespan tortoises, 300 year lifespan sharks, 100 year lifespan macaws, 50-100 year lifespan queen termites, 35 year lifespan naked mole rats, 35 year lifespan bats, 35 year lifespan beavers, 40,000 year lifespan King's holly palnt, 10,000 year lifespan creosote bush, then doing a procedule like high performance liquid chromotography to find any alkanes, partially saturated alkanes (one or more C=C) (might as well find any esterified =O alkene or partial alkene as well) that are at any concentration at the circutory fluid and brain homogenate of these organisms; Then, using chemistry synthesise a few hundred of these esterified alkane/alkene molecules and find out if they amke mouse human tissue culture cells, human tissue culture cells, and entire C elegans organisms live longer; Then order the list of these chemicals on llifespan increase and feed them to mice, orally, with IP injection option ok, with oral valued, to mice at longevity studies to find out if they cause greater longevity at entire mice





Create a tissue culture model of longevity drug increase at mouse tissue culture and human tissue culture: It is possible that there are mouse cells as well as human cells with lifespan of 72 hours, 20 days, 100 days and 200 days at tissue culture, these could then be correlated with the actual lifespan of entire organisim mice to find tissue cultures that are 90% or higher predictive validity at predicting how long a mouse will live with a longevity test drug or chemical; mouse tissue cultures that live 60% longer that with rapamycin, 25-27% longer with royal jelly, 10HDA or also 10H2DA, or also royalactin protein, 5-35% longer with metformin are developed and then these are used, with their faster 72 hour, 20 day, 100 day or 200 day lifespan cycyle times to make screening new longevity drugs and chemicals 300 times, 5 times, and ten times faster than using whole mice; Notably humn stomach tissue lining renews every 72 hours and human tongue surface every 168 hours so I think it is possible to find both mouse and human tissue cells for culturing that have natural 72 hours, 20 day, 100 dy and 200 day lifespans. These could be used to screen hundreds of thousands or millions of longevity drug and longevity chemical candidates at libraries; Technology supporting 1 million, 100 million, and 1 billion well tissues cultures are: a published 1 million channel microfluidic device, a 10 million cells (yeast) per 10 second interval flow cytometer, the way a 1 billion to 10 billion feature commercial integrated circuit CPU has an area of near 1 CM,





90% or higher predictive correlation of tissue culture lifespan and mouse lifespan as a human tissue culture

beneficial to measure peak plasma and trough palsma and plasma half life of longevity drugs and chemicals at mice, optimally at oral administration of longevity drugs and chemicals so humans can duplicate these at humans with oral doses





They could blenderize endoliths, which wikipedia says are microorganisms with million year lifespans and 10,000 year cytodivision cycles, and feed them to mice coated with an enteric coating, they could also see they effect on c elegans, as well as amoeba, pa aeurosomethign (a bacteria that makes that has T2DA and C2DA decenoic esters); also wikipedia says, “Some Actinobacteria found in Siberia are estimated to be half a million years old.”