Longevity technology:

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How many sequential doses of an epigenetic drug cause the epigenetic improvement? Liposomal depot, perhaps attached to an antibody that gloms it to the surface of the lining of the lymphatic compartment could diffuse beneficial drugs, although that seems complex. One possibly as is epigenetic modifying drug palmitate. I do not know if the longevity effects of 10HDA(10H2DA) are from HDAC interference and epigenetic, but if they are then taking a high dose of 10HDA once a month (or some other interval), or like 30 grams of royal jelly which has 10HDA(10HDA) for two or three days once a month could have the same or better longevity effect. There is the possibility that occasional high dose 10HDA(10H2DA) or royal jelly is actually more longevizing from being thorough and of higher activity.

One HDAC2 inhibitor is a nootropic. It is possible that one or two high doses of that HDAC inhibitor a month could

Cause greater cognitive ability.

Notably though there is another version of this. I read histone epigenetics like acetylation can change rapidly, perhaps in minutes, although the other long view also makes sense as people get epigenetics from from their parents or even grandparents. I perceive I read there is longevity epigenetics people get from their parents so a couple days of epigenetic dosing could cause greater longevity effects the person's entire life. A couple days of epigenetic modifier dosing could even cause their children and grandchildren to have greater longevity. At the nootropic HDAC2 inhibitor that causes greater cognitive ability, a couple days of HDAC2 inhibitor dosing could cause intelligence enhancement that is also passed along to children and grandchildren.

Cognitive ability genetics: the genes that the published cognitive ability heightening HDAC2 inhibitor modifies could be g (like iq) intelligence genes. SNPs, alleles, and copy numbers of those genes could be enhanced at the germline or with gene therapy to increase intelligence at humans, that is homo sapiens.

Longevity technology:

I perceive piperine causes greater absorption through the membranes of the GI tract from telling them to be more permeable. Is there anything that could be placed at liposomes along with the active pharmaceutical ingredient (ÅPI) which reach the lymphatic system to make the lymphatic membranes more permeable? It could be piperine again. That lymphatic permeability drug could make other drugs, like rapamycin, rapalogs, or other longevity drugs to be 2-4 times as effective at reaching tissues from the lymphatic system. Combined with the 2-10 times greater effectiveness of drugs that skip first pass hepatic metabolism that could make rapamycin, rapalogs, senolytics, or other longevity drugs 4 to 20 times more active and affordable. Rapamycin that makes mice live 60% longer could be just 12-14 cents a dose based on $40/gram at Alibaba.com .

GSK (Glaxo Smith Klein) has an online page where they request technology ideas. They make Tylenol and some other antipyretic pills:

ela–naproxen (ela-n) is ethynyl liposomal active transport naproxen it is active at about 7.6 micrograms. They could put a dot of it on the outside of regular naproxen pill that is enteric coated so there is an immediate action antipyretic at the stomach but it also activates 11 hours later so one pill lasts 24 hours. Another way to do it is like multiminipill contac™ with ela-n microenteric coat so it dissolves better at the small intestine after 11 hours. Another way to do it is rather than a 7 day palmitate have ela-n attached to a different alkane COOH like perhaps C6COOH

To make another, delayed dose to make 24 hours of naproxen activity, that could do 36, 48, 72 hour one pill dosing as well: Another way is ela-n of three or more types taken simultaneously where each ela-n has a different enzyme-reactive group on the ela-n with a passivating group removed by the enzyme. The enzymes that remove the passivation moiety are enzymes at the circulatory system. The first ela-n gets its passivation moiety removed first and the next ela-n gets its passivation moiety removed next like cumulatively 90 minutes later, then do this with a sufficient elan-enzyme-unpassivated-moieties to get a smooth 24 hour, 36 hour, 48 hour or 72 hour dose curve.

Years of arthritis relief from one office visit: A depot drug form of ela-n, ea-n, which I calculate as having a 7.6 microgram 12 hour dose could put ela-n at an implant (3 year nexplanon-like) with just 16.64 mg of API at the implant. Sensibly and obviously omitting the 2-4 times dosage multiplier enhancement from liposomes, ae-n could be a 33 mg or 66 mg entire API content implant. I think it is possible to make much longer lasting depot implants or even injections, so a decade of arthritis relief from a decade functional implant at one offive visit is possible.

Complementing a decade functional arthritis relief implant is putting the longevity and life preserving peptides AEDG (epithalon) and thymosin at the implant. Epithalon is published as causing 24% greater longevity in mice. The combination of epithalon with thymosin, at intermittent dosing, is published as causing people to be four times more likely to be alive after six years. Epithalon and thymosin are peptides so it is possible screening libraries of variants on these peptides could find versions with fewer mcg per dose.

Another ela-n 24-96 hour antipyretic: put ea-n on the outside of the pill for immediate relief. At the interior of the pill layer, make the 11 hours later dose with dry liposomes that have different numbers of concentric layers at the liposome molecule, so like the 11 hour dose has 11 concentric layers of liposomes ======Ö on it.

It is possible to simplify the ela-naproxen molecule to ethynl naproxen, or ethynyl liposomal naproxen. Ethynylizing sex hormones causes sex hormones at FDA drugs to go from a.625 milligram dose to a 600 nanogram dose, a one hundred times amplification of effect. A cell membrane active transport moiety causes 1000 times greater transport than diffusion. Either of these alone produces microgram active doses of naproxen.

A really simple version of 24-48 hour liposomal naproxen without ethynylization or active transport moieties is to use the way liposomes avoid first pass hepatic metabolism to bring 4 times as much regular naproxen API to the circulation. If that works on regular naproxen that makes a 24 hour dose fit in a pill half the size or at a full size pill up to 48 hours of antipyretic anti-arthritis effect. Dry liposomes could be used.

Longevity technology:

Multiple simultaneous drugs at aged batched mice are a way to make longevity drug API identification faster, and make mouse research as much as 120 times more affordable to produce a p value. Matrix simultaneous drug administration is published, and creating batches of mice, at 8 mice each, two months or less apart in age creates 48 mice, with each duomonthly increment able to generate a longevity increase p value longevity drug. The 2^3 deaggregation mice as steps to find the actual drug that longevizes is a way to do this. Sequential mouse experiments to locate the individual most effective longevity drug, possibly after data on 2-6 months of simultaneous administration of the drugs to new age batched groups of mice. The actual longevization pct of each batch of mice, starting at the first two months p values, continuing to 4 months and six months also gives a number on how much longer the eight and ten month and year interval mice would have to live to continue that particular mouse' longevity gain. This is similar to calculating course grades mid term to find out if a person can still get the grade they prefer, at mice this is how much longevity increase would numerically justify continuing that drug at that mouse for greater than the amount of longevity from other chemicals that have been screened or exist. One API drug longevity quantification; after 4 months you could tell if an Epithalon peptide sequemce variation being screened was 60% more or 60% less longevizing than regular Epithalon. At 4 months you would be able to calculate that the 6 month mice would have to show an 80% gain from the previously measured effects from an age specific effect (like start midlife to cause longevization) to raise that molecular version of epithalon's longevity effect to equal or exceed Epithalon. Similarly if a molecular variant of Epithalon is 60% more longevizing at two or four momths then a side experiment can be started with 8 mice to get a p value on the more effective version. The 8 mouse chronologically colocated experiment can also be raised to eleven mice so three can be used for things like biological samples, psychological testing and other things that accelerate longevity drug development like coaministration of another longevity drug, likely one with a high likeliness of having a different complementary mechanism

sort of like calculating a school grade mid term to decide to keep taking a class

This batched matrix longevity drug protocol can be used on other species as well. 96 well plate fish are vertebrates, age batching can be accomplished on-location without a breeding facility. I have read about fish with a 6 month lifespan, causing the longevity test batches to be either 14 days or a month apart, causing either one month drug characterization or 42 day longevity drug characterization. This also provides the opportunity to medicate the fish before mid-life to explore and find new mechanisms, and measure young behaviors on the longevity drug.

it is also possible to do age batched matrix longevity drug characterization on c elegans. The lifespan of c elegans doubles at some published protocols from 30 to 60 days. The thirty day span can be divided into ten 3 day batches, and the matrix batched longevity increase percentage can be calculated from three age batches in nine days. It is possible that a 96 well plate technology could be enhanced to use computer vision and an acoustic transducer, or just a speaker, perhaps at deciHz (tenths of a Hz) and silent to humans to do the same touch the c elegans with a probe to see if it moves, verifying it is alive in an automated and contactless way.

The near camera automatic sonic probe physically motionizes the c elegans, contactlessly imitating a physical probe. To be less annoying, an intensity that 99.999 percent of c elegans will respond to but not louder is possible. Optimally the sonic probe has a focused beam of less than 1/16th of the plate well area so when the c elegans responds to it the c elegans gets immediate absence of probe stimulation. The sonic probe wiggles the c elegans slightly, causing c elegans initiated motion that is a computer vision detectable motion at the c elegans verifying it is still alive. This replaces a human with a probe and supports full automation of the longevity drug screening process. Automated pipetting could be used to administer a fresh dose of the test chemical. Automated pipetting could also be used to rotate out the water periodically to keep the c elegans well and also at standardized drug concentrations.

I think it is possible to place one to four c elegans per plate. At just four c elegans per plate, i think the p

Noting it is possible to get a p value of .01 if the statement has that much mathematical latitude, " they are still alive", and that the computer vision system can measure 3-7 things simultaneously, with a general enough statement like "the c elegans is above the first standard deviation (compared with normal c elegans) at some automatically measured characteristic" on things like: velocity the c elegans moves when acoustically probed, distance and swimming style of the c elgans when probed, amount of tropism to or away from a laser illuminating part of the well, food enrichment response, possibly even the effect of pipetting another brief-action drug like a neurotransmitter that causes a behavior into the well's water, any visual indicators that change with age at c elegans like skin texture, gonad size, heart rate. Also it is possible to quantify c elegans neurology. Genetically engineering the c elegans used at the screening to have fluorescence of brain based regions or neurons having different emissions spectra fluorescent proteins that the c. Elegans has been engineered to produce. Genetically engineering different parts of the brain or neurotransmitter specific neurons characterizes which systems the longevity drug version being screened could be benefitting. Camera gathered data on which parts of the brain activate in response to a standard harmless stimulus (food, laser, as well as the camera recording the prior to single utilization of the acoustic probe. Each of these, and others has a statement with enough latitude to get a p

Genetically engineered c elegans that indicate their youthfulness can be produced. A fluorescent protein like green fluorescent protein is engineered to be made at the brain as well as separable organ systems like heart, liver, nerves, gas exchange permeability structuress then the size and possibly the activity of these is automatically quantified with the computer camera and compared to preexisting data on young c elegans.

The value of matrix testing the drugs and the effect on the velocity of creation of new longevity drugs: also, notably the highest performing molecule screening matrix group could be considered a compounded (multicomponent actual treatment) drug in its own right. If a rapalogs covalently linked to a AMPK activating peptide combined with a senolytics and an RNAi drug causes much larger longevity increase then it is ok to consider that hroup as one treatment at the mice.

Mouse poop and saliva contain circulatory fluids, indicator chemicals, and mouse cytes that could identify separate complementary longevity mechanisms without disturbing the screening mice. This is a way to heighten the effectiveness of matrix characterization of the longevity heightening from longevity drugs, and, sometimes their combinations, if that is meaningful (note 214 year old whales and mice have almost the same systems, as do million year lifespan endoliths like algae or fungi, as does 40,000 year kings holly with 3650 day trees, so pansystem longevity drugs have validity in their own right while tissue and organ specificity, and things like body compartment, and lipophilicity/hydrophilicity also have comprehensible value, noting senolytics tissue localization, and deprenyl which concentrates most of its effects at a brain area called the substantial nigra, as well as the octopus living eight times longer if it does not have a sex gland (the value of specificity is vivid at the octopus, if there were a "I can tell I have a sex gland" receptor blocking molecule then that one specific molecule, possibly at a particular physical location would cause eight times longer lifespan. That compares with rapamycin effecting mTOR everywhere to cause 60% greater longevity, though also at humans eunuchs live 19 years longer so localization at just a few grams of tissue could also be a human longevity drug.

As a sample that can guide the mouse longevity molecule screening the c elegans or fish matrix screen to generate 99.9th percentile molecules. The three mice out of eleven to do psychological testing and get biological samples from, do positron emission tomography at, as well as matrix combinations that match or combine a brain concentrator with a heart concentrator, are places human cognition applied to the drug matrices can occur, augmenting the simplicity of just mass screening with humans figuring out previously unknown mechanisms from screening successes like finding chemicals at endoliths that longevize mice, and humans basing new drug cores to mass screen variations of.

Drug companies might make a multi chemical ingredient drug based on the effects of the matrix combinations that have the fewest side effects at mice, notably the 3 mice out of a group of 11 (where the other 8 provide a longevity heightening % with a p value) and the most appealing 96 well plate fish physiology measures, like brain and heart similarity to young fish, and including fish progeny well being

Industry competition and publication multiplication: it is possible that when one company gets particular valued results from mass screening a particular kind of thing (endolith or clam chemical variations) that other companies or people that publish do, that there is then more activity in that area, like rapamycin's proliferation of papers and people making new rapalogs, or the 8 papers on the beneficial effects of decanoic acid esters (like 10HDA(10H2DA) and HAEE) effects, this could be treated very simply as a math multiplier of the amount of molecules being screened, if 43 99.9th percentile new longevity chemicals are found then perhaps they will cause 200 new longevity 99.9th percentile higher quality drugs to be produced.

Age batched mice at matrix experiments could possibly be complemented with age batched matrix experiments on marmosets. Marmosets live about 18 years and are a primate with a genome more similar to the human genome. With the most longevizing of the 99.9th percentile and greater mouse longevity quantified, it is possible to get data from marmosets in 2-3 years; midlife marmoset age batches, like 16, 14, 12, 9 year old marmosets, could be characterized to see which longevity chemicals most nearly track along with the benefits seen in mice, that traverse a previously documented progression of benefits most similarly, likely things like reduced heart disease, reduced cancer occurrence, and brain function that is maintained or sometimes improved (rapamycin is nootropic, decanoic acid variant HAEE benefits mental health), it is possible, perhaps to quantify preserved cardiac and brain function, and possibly (possibly otherwise) cancer occurrence decrease at the drugged marmosets that are age batched, optimally the drugs become part of the pharmacopeia people use long before the marmosets get old, but when the marmosets do get old enough to have quantified long lifespan extension above unmedicated marmosets that contributes to the preference for that previously introduced drug, and things that might occur, like the pct of marmosets that avoided ever getting heart disease, cancer or cognitive impairment before a ratioized equivalent of a 114 year old are published, which let's people know about quantified complementary benefits of the drug. The effect of mouse like physiology response being quantified at age-batched marmosets between 7 and 9 years of age or also 14 and 17 years of age being much higher or also nearly identical focuses drug company products around chemicals that will most predictably work at humans.

Marmoset-mouse response similarity tracking also guides companies as to which longevity molecules are particularly beneficial at primates, and so possibly humans, and which have applicability to other areas of medicine and larger usage volume and profitability, noting profitability causes more beneficial longevity and other use drug creation and distribution.

What happens when they feed rapamycin as well as other longevity drugs to octopus? I perceive i read that an octopus that does not have a sex gland lives eight times longer. After octopus sex gland removal rapamycin's effects at lifespan of octopus that have a sex gland compared with no sex gland could be quantified, Octopus lifespan and tissue youthfulness physiology changes from sex gland removal could activate shared homologous genes between octopus and human, suggesting proteins that heighten longevity that could be new longevity drugs. That also suggests that deleterious gene activation at the sex-gland-having octopus, and that the human homologous versions of these octopus sex-gland activated genes could be producing deleterious things at normal humans just living. That suggests that epigenetic drugs like area specific methylases could decrease sex-gland-having octopus' shared homologous gene activation areas activity, bringing the human gene activation and gene product amount nearer to that of an octopus without a sex gland. This would be tested on mice.

Gene products (like proteins), and any circulating chemicals different between sex gland having and octopus absent a sex gland could be proteins and other chemicals that if immunized against cause greater longevity and healthspan at humans. If there is an obvious decrease in any chemicals at a sex gland having octopus compared with an octopus absent a sex gland then those chemicals could be administered, supplemented, at matrix form to age batched mice to find out if those chemicals have longevising effects in 2-4 months. Things that decrease activity of the human octopus homologous genes that activate because of the sex gland, compared to, if there is such a thing, octopus puberty, could also be longevity drugs. Epigenetic modifiers of octopus sex gland networked human homologous genes (methylases and others) could cause greater longevity and healthspan at humans.

They could implant an extra sex gland in an octopus and quantify and qualify the even higher activity than background at an unmodified octopus' human homologous chromosomes to find the particularly likely to be active epigenetic drugs (possibly methylases) and immunizations against the deleterious things that are even more detectable from an octopus having two sex glands to be longevity drugs.



Preventing birth defects: find the mammal with the fewest birth defects or the rodent with least and most birth defects, particularly noting the genes turned on during prenatal development; at the rodents, then find homologous genes and SNPs at humans to find human gene products (possibly circulating proteins) to decrease or increase, to be most like the mice with the physiochemistry of least birth defects.

It could be possible to breed mice with rates of birth defects 1/7 the to 1/16th that of wild mice; at the outdoor mouse dorm have the feeding station computers have an ultrasound probe that automatically scans any mouse that comes to eat, pregnant mice with malformed mouse progeny would accumulate at the database and then their well progeny sterilized. The mice would, as I read mice do, have about 9-11 pregnancies per year and the new baby mice could get pregnant after a month, the feeding stations could also remove non breeding mice from the mouse dorm, after 365 fays of only defect less mice breeding it is possible there would be a % decrease in the number of birth defects, the mice would have a well baby genome that could be compared to the genome of the initial mice with possibly a few locatable genes that caused the reduction in birth defects; homologous genes and SNPs could be found at humans for both less than median and more than median defects; any difference in circulating physiochemical produces a group of chemicals that could be screened to find out if their use as drugs would decrease birth defects, or if epigenetically upregulating their production decreased birth defects, and endogenous chemicals that were associated with birth defects could be immunized against as well as epigenetics like methylation used to decrease the amount of their production. Along with the genes the actual SNPs, alleles, and copy numbers associated with either direction (imaginably the 3rd and 97th percentiles) at mouse genes with human homologous genes could be looked for at human gene databases, like those of health organizations, to find out if human variations on those birth defect producing or birth defect preventing genes had strong numerical associations at humans as well, the human physiochemical differences between the 3rd and 97th percentiles of birth defect rick as suggested from the mouse genes (notably the newly found birth defect reduction genes) would provide a human physiochemical identity source to derive new birth defect preventing drugs, immunizations, epigenetic modifiers and germline gene modifications with. If a human woman had genes that carried risk she could do a cheek swab, have stem cells produced, the deleterious genes changed to the more beneficial defect decreasing versions, then conceive a child with the engineered oocyte which would also reduce the risk of birth defects at all of the human woman's progeny, this is also an opportunity for the woman to enhance the rest of her child's genome.

What would be really amazing is if there were two strains of interbreedable mice, one strain having 1/7 to 1/16 the occurrence of birth defects, the genetic difference between them looked at to find out if there are human homologous genes, and, perhaps the nifty birth defect preventing thing, notably different SNPs, alleles,and copy number variants between the two strains that have similar genetic variations at humans or at humans' particular specific homologous gene versions; at SNPs at two different genes that are particularly active prenatally, the mice with less defects could have a particular two SNP difference from other mice, at humans it is possible some pct of the population has two of the SNPs, one or none, they could measure the amount of birth defects at the humans to find out if those SNPs made a difference at humans, then go through the homologous genes' mouse-human SNP difference (further away from or nearer to each of the mouse' varieties(number of different SNPs; which variety version of mouses multiple snps, are there)) one gene at a time, simultaneously looking at a big database of different human genomes and comparing it to the mice, matching mouse and human SNPs, alleles and copy number variations to humans that gave birth to unwell persons; that finds genes that if engineered to be at mice, can be quantified as to how much birth defect risk they produce then drugs and epigenetic regulators and immunizations and gene therapies used to decrease birth defects at humans.

There is the pleasant possibility, without anything I have heard of to suggest actuality, that the genes of birth defect preclusion (found at the mouse dorm mice) could actually enhance baby wellness causing normal babies to be slightly better than well or to thrive more. There is mathematical support for this, if the number of birth defect reducing genes is near 29 then there is a certain likeliness one or more of the genes is beneficial to the human, perhaps they make more of one beneficial amino acid, have the super high productivity version of a DHA (omega 3 fatty acid) gene, or a hox gene variant that has extra fidelity when transcribed, or liver genes that are 99th percentile at metabolizing risk causing xenobiotics, or maternal genes not just of placenta sufficiency but 99th percentile of placenta optimality (perhaps a differing group of genes or SNPs that variously optimize size, vasculature (notably micro vasculature), development velocity (hormone sensitivity); the genes that availablize nutrients from the mothers body like calcium, phosphorus, and iron could have well baby enhanced versions, the genes that do quality control, like when a woman misses her period for just one month because there was a defective blastocyst or zygote and the quality assurance physiology terminated it; making it so one out of two birth defects were prevented but rather than half of women having sex get pregnant in 7 months, half of women got pregnant when having sex for 9 months, or at the womans option she could either get pregnant almost immediately with assisted reproductive technology or take a pill, or get a depot drug, that caused her to have just 1/3 the chance of birth defects while causing such heightened quality assurance physiology that it took an average woman 19 months to get pregnant. It is also possible the pregnancy quality assurance phenotype and genotype could be made more effective with drugs or gene therapy while minimally effecting the amount of time to get pregnant; SNPs and alleles of the pregnancy quality assurance process, where I think i read but might misremember, that about half of all blsstocysts (or possibly zygotes got naturally terminated at a normal 2019 woman's body, that process if it has to do with quality assurance could be adjusted to heighten quality further.

Dominant along with other, simultaneous multirecessive genes that do the same thing, reduce birth defects, would persist at a population even if there were things that effected various genotypes

Breed different mouse strains to be as similar as possible while presenting the half as many defects difference

Find the primate with the least presence of being then utilize that as a physiological experimental animal, feelingless p-zombie as much as possible. Notably this could be a particular genetics at most or several different primate species, noting there are humans that say they aren't conscious, find the most p-zombie genetics at numerous species then breed or make physiological experimental animals as well as milk cows and egg chickens and caviar fish

Noting human eunuchs live 19 years longer, screening a few thousand sex hormone variations at 96 well plate fish to find 1-100 that longevize without changing behavior could produce a longevity drug screenable on mice. 17 alpha estradiol's published longevity effects at mice without feminizing effects could be a hint.

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the King’s Holly has lived 1.46 million days thus far, other trees have a lifespan of just 3650 days, ceasing to be alive even before a human reaches puberty; Finding longevity drugs based on the 400,000 percent different longevity difference between trees goes with doing HPLC, something better than electrophoresis like laser spectroscopy, electrophoresis or some other thing, to find all the chemicals, proteins, peptides, lipids, in the plants, as well as at human tissue, then finding those chemicals, proteins, peptides, lipids difference between the 1.46 million day longevity plant, the 3650 day plant, and the human;



I read humans share 60% of their genome with the banana, that suggests some plant genes, and plant gene products, and the amount of those chemical plant gene products, have most longevizing molecule versions that can be quantified as to longevity effects at yeast and mice;



finding longevity chemicals: the group of chemicals (and genes) at both the (3650 day tree and the human) that are different than the chemicals that the (kings holly and the human share) are places where the chemicals (and the genes) at the humans could improve and the king’s holly is the source of improvement;



At homologous genes an organisms that noticed it had the 3650 day plant version rather than the kings holly would notice an opportunity to have more longevizing chemicals endogenously produced



finding longevity chemicals: dosing yeast and mice with the chemical that the kings holly gene makes, that the human does not, noting the homologous but different gene, could find longevity drugs;



engineering mice and yeast to make that shared homologous kings holly gene then finding out if it longevizes them produces new longevity genes



This same approach works for finding longevizing chemicals between groups like million year lifespan endoliths comparison grouped with similar-to-endolith with different habitat organisms with 365 day lifespans, 214 year old whales, and whales with briefer lifespans, 400 year lifespan clams, and clams with annual lifespans, and supercentenarian humans with 18 year marmosets;



The genes and gene products (chemicals) that the 400 year clam shares with the annual clam are ignored when narrowing the list of chemicals and genes at the human to find 400 year clam genes with longevity effects;



Now, although the amount of the chemicals matters the same thing can be done with chemicals, proteins, peptides, and lipids at the bodies of the various trees and other organisms



If the chemical is the the 3650 day plant and the king’s holly, ignore it, if it is only at the king’s holly put it in a database;



This works better at varieties of the same species with widely varying lifespans, if there are any species that interbreed but have 2-4 times different longevity, then ignoring the chemicals they share, then making a database of the chemicals only at the long lived variety, then at humans finding if any of the database chamicals



There is a thing here though that kind of makes it improvable, for each 14 million chemicals the kings holly contains, and the 3650 plant overlaps 90% of them, that is still 1.4 million chemicals that might have longevity effects;



I think geneticists who write computer programs already know all about this, but if you have like 100 groups of related-organisms pairs (king’s holly 3650 day tree),(mouse, beaver), (214 year whale, less longevity whale), (human, primate with 1/5th human lifespan) with the group members as far apart as possible as to longevity, and then compare the amount the very different most long lived species converge towards each others gene versions, notably moving away from their species-similar organisim, then you find a possible math convergence around better versions of genes, or better versions of physiochemicals



The high longevity organisms at each of the 100 bowls of 2 or 3 longevity heterogenous organisms each



This technique can be used for other things like, 100 bowls of 2 or 3 mammals each, and the species similar mammals differ as much as possible on behavior, then you look at how the bowl leaders (of very different species) converge on various characteristics, these can be genes, fMRI of brain areas, even things like parenting styles; a human, or niftily, a deep learning AI can then make a list of trends



(Mathematically you would expect the beaver to be more like the mouse, but if the beaver is more like the whale, the human, and the King’s holly then there might be a longevity trend at that homologous gene, similarly you might expect a human to be more like a marmoset than a whale or the king’s holly, but at genes where the king’s holly is more similar that could suggest a “different chemical is better” trend, then noting the upper longevity organisms at each of the 100 bowls each with two or three species in them (mouse beaver, 214 year whale, less longevized whale) (longevized bat, less longevized bat) (human, primate with 1/5th human longevity)



The 100 bowls of three high distalness (long lived, otherwise) yet each bowl with similar species could be repeated at species that have particularly wide longevity ranges, perhaps birds as well; if this finds a longevity trend for a group of genes at very different birds, then the genes the different bowl gnes most share



also the 100 bowls thing of 2 or 3 organisms thing works with longevity chemicals as well, if 100 bowls find like 5000 circulatory chemicals shared at the long lived organisms out of each bowl, then those 5000 chemicals are compared to the chemicals in a human, any of the 100 bowl shared longevity chemicals the human does not (yet) have could be tested on yeast and mice and human tissue culture to find out if they are longevizing; this works with homologous genes as well, if you have 100 bowls of clams, birds, sharks, endoliths, plants, and other things, and the distal organisms in each bowl have and above-chance occurence of shared genes, then those could be longevity genes and a human would compare their genome to that shared at the 100 bowls of very different species; mathematically it would be possible to list in order the genes shared between bowls, and the longevity trend of just that group of bowl-set organisims, so it would be possible to find the likely most longevizing versions of the bowl-shared genes;



at endoliths, 100 bowls as a way to find new human longevity genes has nifty characteristics; endoliths can be bacteria, fungi, algae or lichen, very different species, but they all share lifespans longer than the entire span of human culture; first find briefer species that are most genetically similar to the endoliths, (3 century lichens) (24 hour bacteria) to put in the bowls, with each of the 100 bowls having an endolith; do HPLC on all the organisms chemicals, and sequence the genomes of the 200 or 300 organisms in the 100 bowls, then find where the endoliths converge towards each other, across widely differing species, and away from the other organisms at their bowl,



The chemicals (proteins, peptides, others) that subsets of endoliths produce that have varied amounts of convergence at different subsets of the 100 bowls can be tested as longevity cheimcals;



encouragingly, the 10,000 year lifespan creosote bush produces NDGA, which is also published as causing greater longevity at mice, so chemicals that 100 different endoliths converge on, at unexpected divergence from the other organisms in their similar species bowl, could be longevity drugs and chemicals;



similarly, the long lifespan but species heterogenity of endoliths (algae, bacteria, fungi) if there are any converged on homologous genes could actually suggests genetics of greater longevity at humans, that can be tested on mice, let’s say the endoliths all have mitochondrial DNA that causes mitochondrial uncoupling, then a human could look through a database of mammal genetics and genomes and find out if any mammals had uncoupled mitochondria, and the effect it had on that species being above the median, or high above the median on longevity; (I read that mitochondrial uncoupling actuallu doubles c elegans lifespan, it just seems possible to have a 100 bowl convergence be able to find it as well)



do the “are there any mammals like the converged endoliths’ homologous genes unusualness of form, and, how is it going for them?” thing automatically with computers, also, the technique can be used with any group of species like birds, or tortoises, or even bowls of plants, along with the kings holly there are many trees with multimillenia lifespans



when they do, that version of that mammal gene is unusually likely to be a longevity gene, and using yeast and mouse full lifespan to quantify its effects is beneficial and produces a longevity gene; notably though the gene sometimes makes a product like a protein, endolith converged, then found at mammal genes’ proteins could be screened as to longevity effect; I read that sme endoliths, after you put them in a comfy environment grow rapidly, and a kilogram of cultured endolith might provide enough converged-endolith-gene product to dose shrews, c elegans, yeast, and human tissue culture; (it is kind of nice with 100 bowls you get to skip screening a library, you just culture and gather material from of the species at one of the bowls that makes the converged on chemical, a mathematician would be able to suggest the optimal number of bowls, with endoliths perhaps it is 300 because, if there is convergence on some chemicals, rather than the numerics of screening a library you already have a source)

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How many sequential doses of an epigenetic drug cause the epigenetic improvement? Liposomal depot, perhaps attached to an antibody that gloms it to the surface of the lining of the lymphatic compartment could diffuse beneficial drugs, although that seems complex. One possibly as is epigenetic modifying drug palmitate. I do not know if the longevity effects of 10HDA(10H2DA) are from HDAC interference and epigenetic, but if they are then taking a high dose of 10HDA once a month (or some other interval), or like 30 grams of royal jelly which has 10HDA(10HDA) for two or three days once a month could have the same or better longevity effect. There is the possibility that occasional high dose 10HDA(10H2DA) or royal jelly is actually more longevizing from being thorough and of higher activity.



One HDAC2 inhibitor is a nootropic. It is possible that one or two high doses of that HDAC inhibitor a month could

Cause greater cognitive ability.



Notably though there is another version of this. I read histone epigenetics like acetylation can change rapidly, perhaps in minutes, although the other long view also makes sense as people get epigenetics from from their parents or even grandparents. I perceive I read there is longevity epigenetics people get from their parents so a couple days of epigenetic dosing could cause greater longevity effects the person's entire life. A couple days of epigenetic modifier dosing could even cause their children and grandchildren to have greater longevity. At the nootropic HDAC2 inhibitor that causes greater cognitive ability, a couple days of HDAC2 inhibitor dosing could cause intelligence enhancement that is also passed along to children and grandchildren.





Cognitive ability genetics: the genes that the published cognitive ability heightening HDAC2 inhibitor modifies could be g (like iq) intelligence genes. SNPs, alleles, and copy numbers of those genes could be enhanced at the germline or with gene therapy to increase intelligence at humans, that is homo sapiens.



Longevity technology:

I perceive piperine causes greater absorption through the membranes of the GI tract from telling them to be more permeable. Is there anything that could be placed at liposomes along with the active pharmaceutical ingredient (ÅPI) which reach the lymphatic system to make the lymphatic membranes more permeable? It could be piperine again. That lymphatic permeability drug could make other drugs, like rapamycin, rapalogs, or other longevity drugs to be 2-4 times as effective at reaching tissues from the lymphatic system. Combined with the 2-10 times greater effectiveness of drugs that skip first pass hepatic metabolism that could make rapamycin, rapalogs, senolytics, or other longevity drugs 4 to 20 times more active and affordable. Rapamycin that makes mice live 60% longer could be just 12-14 cents a dose based on $40/gram at Alibaba.com .





GSK (Glaxo Smith Klein) has an online page where they request technology ideas. They make Tylenol and some other antipyretic pills:



ela–naproxen (ela-n) is ethynyl liposomal active transport naproxen it is active at about 7.6 micrograms. They could put a dot of it on the outside of regular naproxen pill that is enteric coated so there is an immediate action antipyretic at the stomach but it also activates 11 hours later so one pill lasts 24 hours. Another way to do it is like multiminipill contac™ with ela-n microenteric coat so it dissolves better at the small intestine after 11 hours. Another way to do it is rather than a 7 day palmitate have ela-n attached to a different alkane COOH like perhaps C6COOH



To make another, delayed dose to make 24 hours of naproxen activity, that could do 36, 48, 72 hour one pill dosing as well: Another way is ela-n of three or more types taken simultaneously where each ela-n has a different enzyme-reactive group on the ela-n with a passivating group removed by the enzyme. The enzymes that remove the passivation moiety are enzymes at the circulatory system. The first ela-n gets its passivation moiety removed first and the next ela-n gets its passivation moiety removed next like cumulatively 90 minutes later, then do this with a sufficient elan-enzyme-unpassivated-moieties to get a smooth 24 hour, 36 hour, 48 hour or 72 hour dose curve.



Years of arthritis relief from one office visit: A depot drug form of ela-n, ea-n, which I calculate as having a 7.6 microgram 12 hour dose could put ela-n at an implant (3 year nexplanon-like) with just 16.64 mg of API at the implant. Sensibly and obviously omitting the 2-4 times dosage multiplier enhancement from liposomes, ae-n could be a 33 mg or 66 mg entire API content implant. I think it is possible to make much longer lasting depot implants or even injections, so a decade of arthritis relief from a decade functional implant at one offive visit is possible.

Complementing a decade functional arthritis relief implant is putting the longevity and life preserving peptides AEDG combined with thymosin at it

A peptide humanin, as well as MOT-c mitochondrial derived peptides (MDP) that is beneficial to screen as to being a longevity peptide that anti aging things and aging things simultaneously, the crummy part is it makes old cytes make old cyte chemicals, like some interleukins, the longevity thing it does is be opposite ilgf, growth hormone and Alzheimer's amyloid, they have, as far as I know, fed it to organisms to find out if the mice live longer and if they do, how much; notably though if MDP actually causes the things senolytics do then the opposite of a MDP, a receptor passivator, or an immunization against MDP could be a longevity drug, the MDP and antiMDP could be administered to different mice to find out if either is a longevity peptide



I saw a graph suggesting longevity chemical spermidine is an acetylase (histones) adjustor, it is possible that the

[Treon Verdery]

Longevity gum, “More than 100,000 tons of chewing gum being consumed every year.”, of cavity preventing xylitol gum, “dentists from all around the world recommend daily ingestion of up to 5g of xylitol (around 9 mints or 3-5 pieces of gum per day” So if people chew five pieces of gum per day, 1825 pieces a year; 730 million or 1 billion gum chewers is plausible at a little over 10% of 2019 global population, and at 1825 pieces a year that is a little less than 2 trillion sticks of gum a year, at 20 pieces of gum each 24 hours per chewer that is 8 trillion pieces of gum. At a one cent premium per piece of longevity wellness gum that represents 80 billion us$ annual revnue from longevity and wellness increasing chewing gum.



AEDG chewing gum, also if a levo and dextro amino acid version of AEDG is found to be longevizing and wellness causing then AEDG could reach the GI tract for absorption.

Lithium at gum: Lithium in the water supply is correlated with people living longer, and makes laboratory nonvertabrates live 9-20% longer. If a flavor neutral or yummy lithium gum additive can be found, which could possibly arise from linking a 10,000 times sweeter than sugar sweetness peptide to lithium at a stomach dissolvable lithium chelator molecule, then at 5 sticks a day, and 5 mg of lithium per day, then 1.001 to 70 mg of delicious combined lithium/sweetness peptide/chelator molecule would be at each stick of gum.

Also, they can put anything, at perahps 200 mg at liquid center gums like chewels.

Some chewing gums may already have a peptide/peptone/protein component. calcium casein peptone is a texturizer at chewing gum, “at a use level up to 5% wt/wt”

Production of beneficial drug peptides from milk (casein) and grain (gluten): Modified proteases like trypsin could make different digestion products, some of which are drugs. Genetically engineered organisms would make the new proteolytic enzymes with customized products, which would then turn other things into beneficial medical peptides affordably. This brings Genetically engineered production’s product affordability to natural products.

Even more affordable than engineered enzymes: plants that make modified gluten with trypsin or pesin dividing regions that repeat, with a peptide of value between them: Also, as plants produce glutens, it is possible that producing Genetically engineered organisms with the sequence (trypsin or pepsin cleavable location) -peptide of value-(trypsin or pepsin cleavable location): as the peptide-of-value-polyrepeat at genetically modified gluten could produce a highly affordable source of beneficial peptides.

Modifications of gluten to produce valued peptides released from digestion with ultraffordable already available bulk trypsin or pepsin:As a system the technologist would just swap in the amino acid sequence of interest at the -peptide of value- location at the genome. During about 2005 AD the barley lab I worked at would get about 3 successfully genetically engineered plants for every 100 prepared (embryo sliced, soaked in transfection liquid, agar placed) barley embryos suggesting immediate rapid production of over 200 different versions of gluten with different -peptide-of-value- per researcher per year using very simple technology I was able to use with 1 hour of training; the technology I used likely has transfection efficiency and hourly production with new variant protocols that are 10 or 100 or even 1000 times more productive from automated slicing and multiwell plates.

It could be nifty if taking a protein with amino acid (peptide-like) sequences that already have bridges (like S bridges or different bridges) and then putting something like a trypsin or pepsin-division sequence at the four corners of the bridge :-:, would then produce a variety of different customizable bridged peptides easily and reliably; they could even make an enzymatically attachable spacer amino acid string of genetically variable length to place between the two bridge sides like n or n that would predictably provide the right distancing of briding amino acids to favor amino-acid bridging. This likely already exists.

Can a trypsin or pepsin (notably a chemical variant that does not interact with the protein source, like milk, until the hydrogen ions in the stomach modify the trypsin molecule) be swallowed with a food, like a trypsin or pepsin milkshake, to produce a biologically active peptide in the stomach or even other parts of the GI tract?

Casein, the 80% of milk’s protein protein is processed like, “manufacturers combine casein with calcium hydroxide at high alkaline levels and dry the protein” So could a non pH/pOH molecule like a carbonium ion, a methyl ion, or an ammonium ion make a novel protein chemical, that possibly with enzymatic digestion becomes a beneficial drug; sort of like casein with ammonium makes a bunch of c=c-c=c peptides that have ammoniums on them, thus looking sort of like metformin, a biguanide with numerous c=c, That goes with preconcentration, predigestion protein sources with lots of gaunidine could produce metformin function-similars with ammonium ion (pNH3/pNH2) treatment. This could also be used on digests of the protein gluten.

At casein as well as gluten they could screen every n sized group of peptides available from a library of possible published custom digestions of the protein (producing like all 7 mers, all 40 mers etc) against activity databases to see if any of them are drugs, they could also massively parallel make molecular receptor attachment models of some amount of casein’s N possible truncated peptide constituents to find new drugs that could be made from casein or gluten.

Opiod peptide from digestion of milk: a 3 (H-Tyr-Pro-Phe-OH) ,4,5,6, or seven-amino peptide (H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-OH) like beta-casomorphin-7; perhaps some opiod peptides are actually enjoyable, which are also minimally harmful, perhaps from localizing at only particular brain regions like the nucleus accumbens; It is possible that nonCNS opiod peptides relieve discomfort without having cognitive or behavioral effects. I perceive just putting a hydrophilic lipophobic length of, or external hydrophilic or lipophobic tertiary structure outer layer of amino acids or a polyglycine length on a peptide will keep it on the body side of the blood brain barrier, so that could be a thing that relieves discomfort or could aslo provide anesthesia.

A map, possibly constructed with positron emission tomography, or other approaches, of a screened library of which peptides concentrate at what brain regions, as well as what body regions, and an immunocolorization map (or niftier technique) of peptide localization at each cytotype and tissue type would be beneficial to the creation of beneficial drugs, notably those producible from gluten digests and probiotics and gene therapy as well as possible germline modification. Nootropic: numeous nootropic peptides are described online and at the scientific literature, https://ultranootropic.com/ ,would vasopressin, thymosin beta 4, semax, noopept, as well as many other peptide variants that only localizes at the frontal lobes improve cognition and memory and other cognitive things without effecting emotional capability (limbic areas) or bodyside functions (cerebellum, brainstem)?

Noting CNS effects on longevity, screening all nootropic peptides to see if any of them are also longevity producing peptides could find new longevity drugs, as well as amino acid sequences that van be function mimiced with peptide mimetic drugs to produce completely new lifespan lengthening drugs.





also, “Casein peptides are used for high blood pressure, high cholesterol, anxiety, fatigue, epilepsy, intestinal disorders, cancer prevention, and stress reduction”

Could casein be used as an ion transporter to different cytotypes?

polyprotic acid, or a polyhydroxyl base



s from changing something like “sodium (salt of) Also, they can put anything, at perhaps 200 mg at liquid center gums like chewels.

Do any oligosaccharides (like sugar mini-polymers) have drug effects? Are any of them longevity or wellness effects like polyribose might have, polyribose molecularly sapced NR or NMN that turns to NMN at cytoplasm, as a possible enzymatic or some benefit to the brain as a food, or fostering beneficial probiotic growth,

Previously described are possible artificial colors that heighten wellness or longevity to be used as food additives. c=c-c=c-c=c structures are frequent at some colorizing chemicals. Also, a longevity version of bright yellow B vitamins could be possible.



Microsugar lancets like at applique needlesless drug delivery could have some activity at gum. That suggests a pack of gum could immunize against atherosclerosis, perhaps a dose per decade, or even a dose per century.

A month of gum chewing with highly localized, less than than mentally perceptible effects on feeling normal, senolytic could be a one month longevity treatment.

Although candy with immunoactive material at microlancets could also do immunizations, it is possible swallowing immunobeneficial or other longevity technology gum could be beneficial.

AEDG linked to carbohydrates; lithium linked to carbohydrates, ribose linked to AEDG could concentrate AEDG at the heart, providing benefit.

AEDG linked to lactate or lactic acid could concentrate at the brain, causing benefit; as a minute amount at food, gum, or candy, concentration of AEDG at the brain could provide benefit, notably though AEDG has something to do with pineal gland chemicals, so brain concentration could permit lower doses, be more likely to provide projected benefits, possible enhance or otherwise effect fertility (50% greater conception rate from melatonin at IVF)

NGF and BDNF heightening 2 amino acid peptide, noopept, “In animal studies, Noopept has been shown to stimulate the expression of two important cognition-related chemicals, Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF).”

Could those two amino acids at noopept, proline glycine, or any other nootropic peptide, be used when attached to other drugs cause high utility brain localization, “Brain-Derived Neurotrophic Factor (BDNF) has a similar role to NGF but is primarily active in the hippocampus, cortex, and basal forebrain, areas of the brain that are vital to learning, memory, and higher thinking”, also, “readily crosses the blood-brain barrier”, so attaching 2 mer (prolyl glycine) noopept to 3 mer opiate peptide (Tyr-Pro-Phe) making 5 mer pro-gly-tyr-pro-phe as a brain concentrating opiate peptide?



Proline-glycine could be an effective way to get numerous other drugs to pass the blood brain barrier, perhaps phenibut-Pro-Gly could work at orders of magnitude less milligrams per dose, and it is also possibly Pro-Gly causes drugs to pass the ovary-blood barrier as well, improving fertility drugs and possibly making contraceptives even more affordable on a $/Kg manufacturing basis.



Protein Kinase RNA-Activated inhibitors, or PKR inhibitors like C16 are peptides described online as causing new path learning after one session as compared with several sessions for unmedicated mice; could PKRI be used to localize other drugs to the brain areas that cause the “one training session works as well as several” effect? CART peptide linked to PKRI is one possibility for a new nootropic that also makes learning with many fewer examples or less practice duration possible. Even linking Pro-Gly (noopept) which increases BDNF and NGF to PKRI like C16 could cause those rapid-learning neural areas to grow causing lasting increases in intelligence. PRKIProGly can be constructed and ordered online.



Are there any peptides that pass through cartilige and joint tissues rapidly, these are different than “blood brain barrier”, but if there is any preferential transport there might be peptide that does that at joints; chondrotoin, MSM, hyalonuric acid and others could all be linked to such a joint transport protein. This could also heighten migration of other drugs. This would treat or prevent some joint decay, causing more youthful joint form and usefulness.

Genetically engineering a plant that treats schizophrenia and psychosis: There could be a peptide, findable at a library of less than 576 two mer peptides that specifically effecs 5HT receptors, Latuda which functions only at HT2 receptors and is absent effect on D1,D2, orther dopamine receptors, causing fewer side effects, could perhaps have a functionalike peptide, and then the peptide engineered into plants, brewing yeast, yogurt, vaginal probiotics, and oral probiotics, making antipsychotic medication grwoable and able to reach more than 70 million people globally. Of the Pro-Gly two amino acid noopept, online it says, “Noopept modulates the activity of both AMPA and NDMA receptors”, so they could screen a combinatorial library of all the 2 unit peptide combinations of 24 different peptides, which is near 576 different peptides on 8 mice each, to get p<.05 at behavior change, like nonpsychotic begavior, and immunocolorization mapping of the brains and bodyside nerves to see which peptides caused localization at dopamine neurons, much the way Pro-Gly concentrates at AMPA and NMDA neurons. Also, as serotonin neurons have many published activities these serotonin active or also serotonin neuron localizing neurons could have numerous beneficial drug effects.

Although noopept Pro-Gly is functional at 10mg oral dose, could a leve-dextro version of the amino acids make it omit being digested, causing a nootropic doasge in the micrograms?

Similarly, could a levo-dextro version of opiate peptides omit being digested thus causing microgram functional dosages? Also, do opiate peptides work more enjoyably if snorted or vaginally applied, or made to be a buccal absorption alginate gel mouth coating?

A variety of ribosomal activity nootropics that might, or might not function like PKRI C16, Protein Kinase RNA-Activated Inhibitors,“What makes PKR inhibitors an EXTREME example is how it works. It essentially disables a security feature of the brain that helps to prevent viral infections” suggests the possibility that either genetic material reaching ribosomes omits a prescreening of some kind, or that the ribosomes work more rapidly, or that tRNA availability goes up,



Longevity technology: Dastinib with querectin are Senolytics that benefit the brain:

The senolytic: is described as, “Senolytic treatment of AD mice selectively removed senescent cells from the plaque environment, reduced neuroinflammation, lessened Aβ load, and ameliorated cognitive deficits. Our findings suggest a role for Aβ-induced OPC cell senescence in neuroinflammation and cognitive deficits in AD, and a potential therapeutic benefit of senolytic treatments. “dasatinib and quercetin (D + Q), can selectively eliminate senescent cells from pathological tissues”

At mice, the senolytic dose was 12 mg/Kg of dasatinib and 50 mg/Kg querecetin, oral gavage with PEG/saline vehicle; so perhaps 70 mg per day of D for a human, utilizing the 1/12 mouse dose thing, and 350 mg of querecetin per day. Dasatinib is prescribed for 12 months or possibly longer as an anti-cancer drug, but the senolytic dosage duration at the mouse experiment is 9-10 days. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605052/

Dasatinib causes mice on an 11 week long dose to be better at learning motion pathways, at (youngish) 3.5 month old mice, rigged to be messed up, “In peripheral organs, partial elimination of senescent cells (~30%) is sufficient to restore tissue homeostasis and function in disease models and during aging7,29,30. We next determined whether longterm intermittent senolytic treatment could ameliorate Aβ plaque pathology and/or improve cognition in APP/PS1 mice. Beginning at 3.5 months of age, female APP/PS1 AD mice were treated with either D + Q or vehicle once weekly for 11 weeks (Fig. 5a). Hippocampus-dependent spatial learning and memory were evaluated by testing the mice in the Y maze immediately before, and at the 6- and 11-week treatment time points, and mice were also tested in the water maze during treatment week 10. Mice were euthanized at 11 weeks and their brains processed for biochemical (one hemisphere) and histological (the other hemisphere) analyses. [and then it says] Compared with vehicle-treated APP/PS1 AD mice, APP/ PS1 AD mice treated with D + Q performed significantly better in the Y maze at both the 6- and the 11-week time points (Fig. 5f). In the water maze tests, D + Q treatment enhanced memory acquisition (more rapid learning of the location of the hidden platform) and memory retention in the probe trial” Notably at a graphic at the paper, dasatinib with querecetin caused large but then identical learning effects; at day 4 of cumulatively learning a pathway finding task the drugged mice were approximately 62% better learners, but at day 5 they were identical.

At a different paper, “senolytic therapies could be administered intermittently, serving to reduce the senescent cell burden by treating quarterly or even annually, which minimizes the risk of side effects”, “Treatment of mice with dasatinib plus quercetin (D + Q) improves cardiac ejection fraction and increases vascular reactivity in old mice after a single, 3 day treatment course [30,34]. In addition, D + Q treatment decreases vascular calcification and increases vascular reactivity in hypercholesterolemic, high fat diet fed ApoE−/− mice after three monthly 3 day treatment courses”

They could see if a different chemotherapeutic drug, nilotinib, that works on the same kind of cancer as dastinib is a beneficial senolytic, possibly with nonoverlapping activity at different body cytes or body tissues.

Localization peptides or proteins attached to senolytics like dasatinib could cause even greater benefit. Pro-Gly could cause brain concentration, noting that dasatinib is published as heightening learning ability it is perhaps beneficial to have a senolytic reach the brain. Chondrotoin or MSM molecular moeity on senolytics could cause greater joint youthfulness function, reduce immunoreactivity and sequelae; the cytotypes senolytics remove are published as linked to bone-joint illness, suggesting senolytics could produce younger phenotype function at bones and joints.

Fisetin is a senolytic, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/ “The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit.” as well as, “chronic administration of fisetin to wild-type mice late in life improved tissue homeostasis, suppressed age-related pathology, and extended median and maximum lifespan”, “This result, similar to a recent report on the combination of D ± Q, is the first to document extension of both health span and lifespan by a senolytic with few side effects, even though administration was started late in life.”,

Dose: “mice were fed Teklad 2020 chow (Envigo, Madison, WI) prepared with or without 500 ppm (500 mg/kg) of fisetin (Indofine Chemical Co., Hillsborough, NJ) by Envigo. Co. (Tampa, FL). For oral administration of fisetin, mice were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol or vehicle only by gavage.” That represents 7 grams of fisetin every 24 hours at a direct, non compensated for mouse size dose, or 583.3 mg every 24 hours at a compensated mouse dose. At the fisetin placed at food, “diet with or without supplementation with 500 ppm (500 mg/kg) of fisetin, ad libitum (approximately 60 mg/kg fisetin per day). The mice were exposed to a fisetin diet intermittently from 6 to 8 then 12–14 wks of age” which could be communicating that each Kg of mouse (that is a lot of mice) got 60 mg of fisetin, so 4.2 grams per day, without mouse division number, or 350 mg per day at the mouse dose equivalent convention number. On ebay, fisetin is $22 for 10g.

At the paper, 20 micromolar fisetin has twice the cytonumber reduction as 5 micromolar fisetin at cultured cytes treated for 48 hours, and the difference in messed up cytes goes from no effect at absence of drug to 1.1/.5, or about 55% reduction of messed up cytes at 20 micromolar.

A different graph displays fisetin at cultured cytes’ senolytic activity as 1.3/.4 or 69% reduction in senolytic cytes.

They measured the senolytic activity of 11 different chemicals, fisetin at 69% was more effective than curcurmin as a senolytic at about 50% https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/

It is possible that sequential or simulataneous senolytics could benefit survival and promotion of youthful cytotypes, so curcurmin with fisetin, or at a sequence with each other could be beneficial. Taking them simultaneously could possibly work better as it is possible the nonoptimal cytes express immunoattractants while processing senolytics, and doubling the amount of immunoattractants or simultaneously producing different kinds of immunoattractants could cause greater immune response that removes nonoptimal cytes.

Notable for fisetin in food compared with once a day oral dosing, fisetin has a plasma half life, so keeping plasma levels high and steady could be beneficial as the food only had 350 mg in it, compared with the 583 mg in the once daily dose, I do not know if they had identical senolytic activity yet though.

If a human eats .5Kg of carbohydrates that is 2000 calories, and at mouse dose would have 250 mg of senolytic fisetin, suggesting the 583.3 mg a day dose is better, noting at cultured cytes doubling fisetin concentration doubled senolytic acivity. also, at a different paper dasatinib was more effective at higher doses.



An immunization could have one of the effects of senolytics, “Senescent cells can develop a senescence-associated secretory phenotype (SASP), consisting of pro-inflammatory cytokines, chemokines, and extracellular matrix-degrading proteins”, immunizing against extracellular matrix-degrading proteins could cause greater tissue functionality longer, and senolytics are researched as causing greater wellness and younger phenotype. extracellular material might be particularly reachable with antibodies. It is possible that as some immunizations last as long as a person, immunizing against extracellular matrix degrading proteins could be a one dose lifespan increasing and wellness increasing immunization, possibly functional at farther than postpubertal ages even when given to a child, during the period when people routinely get immunizations and parents highly prioritize immunization activities and coverage. It is also possible that “matrix degrading proteins” have an effect on dermal cytes and structure, which I perceive I read have something to do with the word “matrix proteins”, that causes this possible longevity wellness immunization to also be a beautification and youthful appearance sustaining possibly one dose treatment, heightening popularity and voluntary use. The other chemicals mentioned, “pro-inflammatory cytokines, chemokines” could also be immunized against to benefit longevity, wellness, and phenotypic youthfulness; I pereive there are a number of these cytokines and chemokines, so a list of which have the highest mass/volume concentration both at the circulatory system and outside, right next to the cytomembrane at the intracyte space, and then immunizing against those, could concentrate effectiveness although cytotype and tissue specificity could make immunizing against all of them notably more effective; One benefit of immunizing against a multi digit (2 digit? three digit?) number of chemokines and cytokines is that some of them may have multidecade effective immunization coverage while others might have different immunization coverage, This partial yet long duration removal of deleterious cytokines and chemokines and matrix protein harming chemicals could actually interrupt and derail any harmful processes where the deletarious cytokines, chemokines and matrix-messing up chemicals effect each other, build on each other, or saturate body repairs, from combining or cascading each other’s effects. A person that is good at math and algorithms could look at a biochemical network, then come up with a minimum number of items to remove, at certain chemical-link distance from each other, to break a network effect, cause a different group average, or modify the persistence of an emergent effect, sort of like whats the fewest steps to wipe out a deleterious eignevalue? Immunizing against that group of chemokines, cytokines or matrix-protein messer-uppers could do that math, causing greater longevity, wellness, healthspan, and youthfulness of phenotype.

Protein or peptide linked drugs could traverse vascular plaque cytopiles to deliver beneficial drugs that shrink of remove vascular plaque blobs and cytopiles and be a cardiovascular wellness drug, “[senolytic]reduces senescent cell-like, intimal foam cell/macrophages in vascular plaques”; they could screen the 526 peptide library of 2 unit (mer) peptides formed from 24 amino acids to find out if any cause preferential traversal of atherosclerotic plaque cytopiles and possibly cholesterol coatings. lipophilic peptides could be better at traversing cholesterol coated or layered cytopiles. lipophilic peptides linked to physiologically harmless immunocyte attractants could cause macrophages and WBCs to find atherosclerotic plaque particularly attractive to glom and remove. Making a protein digest of bacterial cytowalls, then linking them to lipophilic peptides could cause the immune system’s rapid and effective response to bacteria to be directed at atherosclerotic plaque, causing greater wellness and possibly improving cognition with improved CNS circulation, as well as reducing risk of cardiovascular disease. Immunizing against cholesterol works on rabbits to reduce cardiovascular nonoptimality, immunizing against plaque blobs could remove them: also just as there are many different velocities and “brush strokes” to cleaning off a nonbiological item, different velocities of immunoresponse as well as different biochemicals to remove (immunoglom) first could be tested to find the immunocleanup of vascular plaque blobs that was most beneficial and with the least risk.

a novel senolytic mechanism with a “pick preferred candy out of a pile before getting on a school bus” metaphor: Some chemical transport channels of the exteriors of cytomembranes are possibly durably pluggable with molecules, these molecules are also consructed to have a lengthy molecular tail that the immune system recognizes and is reactive to. It is possible that deleterious cytes like the kind senolytics remove, as well as scar or encapsulation tissue cytes, as well as piled up cytoblobs at vascular arterial plaques, have greater molecular transport of some specific chemical. Then, I perceive that when a person gets a harmless viral cold, that they get symptoms for 3 days before the symptoms get better, that suggests that a 2019 AD human’s immunse system takes 72 hours to produce the antibodies to remove an infection.

Labelling many things, then using a gentle wash to provide unwell/well cytocontrast: Decorative plugs that occupy a transport channel at the cytomembrane diffuse away, with a half-diffused amount at 24 hours, so 96 hours after the labelling dose, only 1/8 as many decorated plugs are on cytes. If the deleterious cytes stared with 80 plugs per cyte they will still have 10, but the cytes that only had 6-8 decorater plugs will have about 1 or zero.

Noting that senolytics increase longevity, wellness, healthspan, and cause younger cytophenotype and tissue phenotype: a new kind of senolytic: Have the person eat or be dosed with an immunoreactive chemical that has a cytomembrane molecular transport channel plug that is like 3 to 40 times more likely to plug up a molecular transport channel at the external cytomembrane and accumulate at a deleterious cyte like the kind of cytes senolytics terminate. Noting well cytes and deleterious cytes differ as to their transport channels (senolytics are previously published as reaching their goals preferentially) Give them a big enough dose so that each deleterious cyte gets say 80 antibody-reactive plugs for every 2 at a well cyte, or even 90 antibody reactive plugs at a deleterious cyte for every 30 at a well cyte. Then give the human a big dose of the decoration (the antigen without the plug part) to activate the immune response, doing this after 96 hours of gentle diffusion washing away some of the decorator plugs, the big dose of plugless decoration causes a large immunogen response, after most of the well cytes are absent decoration while the deleterious cytes are still immunoreactive.

Also, along with the activation dose of decorator (absent plug) antigen to produce an immune response after well cytes immunoreactivity is decreased, It is possible to use the body’s apparently ordinary 2019 AD 72 hours to make an immune response to a viral cold effect, then have that 72 hour spontaneous immune response glom to and remove the decorative plug labelled cytes once 96 hours have progressed, the body has produced antibodies after the 72 hour viral cold-like process, and well cytes have only zero to perhaps 3 decorated plugs compared with 8 at a deleterious cyte. The deleterious cytes have been senolytically removed, and could even possibly be removed on a “senescent cytes have different transport channels” basis, the thing that makes it a new senolytic is that it terminates cytes like a senolytic without an external drug toxin; similarly this could be a way to treat cancer, removing some of the oncocytes. Noting that some mechanism at senolytic chemotherapeutic drugs like dasatinib get preferential effect (thus likely membrane transport) at senescent cytes, and then the senolytic drugs terminate the senescent cytes, it is scientifically sensible to think senescent cytes have different molecular transport channels, or quantities of ordinary channels.

Plugging the transport channel while attracting immunoreaction, when the immunoreaction can be times or sequenced creates kind of algorithmic numerical advantage in removing deleterious cytes. Possibly a plug that resides for just hours or 96 hours would preferentially remove deleterious cytes while using up all the circulating beginning antibodies to the decorated plugs; The decorator-plug immunoreactive cytes can use up all the circulating antibodies, that lack of antibodies causes the immunoreactions effect on well tissue to be minimized, which maintains organism well being. At some numerical versions, noting each deleterious cyte has more than 8 times as many decorative plugs on it while the well tissue only has between zero and 1/8th the sites and immunoreaction, After 8-24 hours after the 72 hours before the body makes its own antibodies to the plugs, at that 96 hour chronoregion, all the existing amounts of anti-plug antibodies are utilized and there are near zero circulating antibodies, so there is an absence of further antibody glomming action on well cytes and tissues even though the immune system has been activated, activated with the same effective intensity as a response to a viral cold.

So like 100 milligram of antibodies gets used up on the highly 8:1 decorated transport channel-blocking molecules, while well cytes have a graphical distribution displaying the number of glommable plugs as centering on just one or even zero; It would take 24 hours to make another entire 100 milligrams of antibodies, so noting the decorated plug molecules wear off before that 24 hours while the body is producing the next 100 mg, the 24 hours that pass make cause just 1/4 of 1/8th the decorative plugs to be at well cytes. The well cytes only get 1/32nd the immunoreaction cleaning dose of immune system response. Meanwhile the deleterious cytes still have a plurality of decorative plugs at each cyte, labelling them for glomming and removal.

Longevity technology:

So is there a sequencable series of natural allergens, or even easy to find and get harmless colds that can be screened, like a screenable library, to do this glom at the places beneficial senolytics are active, gently wash well cytes to experience immunoharmlessness, and also up immunocytes purposefully to terminate the labelled deleterious cytes? That would be a sequence made from preexisting viruses and allergens at the 2019 AD typical population, where a human body proceeding through that sequence actually gets greater longevity, wellness, healthspan, and youthful phenotype.

So, uh, BCG, and possibly, MAO-B receptors on blood cyte surfaces, and perhaps there is something natural that occurs at capillary epithelial cytes; could blenderized pollen, perhaps with oil to make GI tract passaging liposomes, cause immunoreaction at the circulatory system? Also what about things like mushrooms, fugu, and other species immunoreaction physiological products? Are there things like blenderized e. coli variations of particular kinds that cause varied immune response, which can be bred or engineered to be longevity, healthspan, wellnes,, and youthfulness of phenotype beneficial senolytics, because they have different lipopolysaccharides on their membranes?



Find the receptors or molecule transport channels that are at the exterior cytomembrane of senescent cytes, the kind longevity, wellness, healthspan and youthful phenotype producing senolytics effect. Optimally find external cytomembrane molecular biology characteristic structures, senescent cyte-only receptors and molecule transport channels unique to senescent cytes. Then gather a bunch of those unique molecular biology object-features, like proteins, molecule transport channel membrane protein structures, or possibly lipid raft like cytomembrane fragments with a stable, typical to living structures of a molecular biological form of the kind of deleterious cyte terminating senolytics terminate, Then screen libraries of wild-type bacteria, fungi, plants, and even virus products to find out if they effect, modify, block, cause hypertransport at, or disintegrate these molecular biology structures.

Also, a novel thing, place a bunch of the actual molecules and proteins that are the unique biomolecular structures of the kinds of cytes senolytics terminate, at a culture medium, perhaps a (1000 times 1000) million multiwell plate, that contains a wide survey of bacteria, wild yeast, and variations on what humans think of as beneficial bacteria (probiotics); possibly use micropositioning to place a zone of molecular biology unique structures, a diffusion gap. and then a bacterial growth area: this causes material that diffuses across the zone to be measurable as to its quantitative effect on the unique molecular biological structures of the kind of cytes senolytics direct their effects at; When some of the million sample multiwell plates find bacteria, fungi, even viruses hosted by human tissue culture cytes products’ or other materials that cause plugging, blocking, hypertransport amplification, or disintegration of the unique molecular biological structures of the kind of cytes senolytics terminate, then organisms that produce new senolytics have been identified and can be quantified as longevity, wellness, healthspan, and youthful phenotype producing drugs. These wild type organisms can also be bred to have much higher amounts of senolytic chemicals. That is a new source of senolytic drugs.

As a technology, an immune response generating functions-like-a-senolytic yeast beverage or yogurt, plant, or plant pollen, bscteria, or even physiologically and attentionally nonperceptible dermal bacteria, similar to a probiotic, that is a senolytic from immunofunctioning, that is the immunosensitizing bacteria, plant, fungi or even virus causes greater longevity, wellness, healthspan, and youthfulness of phenotype like senolytics do. The humans, that is person’s or people’s immune response to optimally, the organisms or ok, but less nifty as it goes with actual human sustained production of concentrates, organism material concentrates, where both and either of these causes the immune system to be sensitized to glom and terminate the kind of cytes senolytics terminate.

So, perhaps: blenderized e coli membranes, combined with cytomembrane molecule transport channel plugs that preferentially populate deleterious chemokine and deletarious cytokine export channel (efflux) transport channels, also combined with some oil to make liposomes that make it through the GI tract;

So where do the at-wild, at 2019AD society, efflux blocker molecules come from? Organisms at a culture medium with chemical travel zone and an area of chemically changeable molecular biology structures to measure the modification efficacy of each of the organisms forms is described. As another source of efflux channel blocking molecules that are combinable with immunosensitizing decorations on the efflux blocking molecule, for immunoglomming and removal, which has a senolytic function effect.

It seems like it would be possible to screen a library of naturally occuring materials and molecules,proteins, peptides,andother things, as well as genetically engineered materials like new or enhanced proteins and peptides, to find out if there are any that plug the efflux channels that are effluxing deleterious biochemicals.

It might be that to a molecular biologist this is sort of easy, like “the transport channel is n angstroms wide and w angstroms tall. Anything hydrophobic/hydrophilic you make with an angle bend, a beta sheet or an alpha helix on it will block the efflux channel of that size and form. If you make a 20 amino acid peptide tail and put iton the plugging protein, you can use an amino acid that is absent any environemental or body-wide previous immune sytem antigen stimulation, or immune system activity. Immunocytes that react to the unique 20 mer peptide, after the “immune system alerting dose” are unlikely to react to any other physiological biochemical, minimizing immunological reactions drift, thus keepin nearer optimal human, immunofunction, human longevity, human wellness, and youthful phenotype form at the human.

The technology is that if just those cytes are immunoterminated which have a bunch of efflux channels where deleterious cytokines, chemokines, and matrix protein messer-uppers are effluxed, then that immunotermination functions like a senolytic:

Gene therapy, that transfects and terminates deleterious cytes with something like apoptosis, gene therapy that produces immunoequivalents to senolytic drugs, or gene therapy that actually produces proteins or peptides that are senolytic in their own right. Technology of senolytic longevity, wellness, healthspan, and phenotypic youthfulness of form are developing. At 2019 AD, at any deleterious cyte where a senolytic accumulates at but previously did not terminate as it would more optimally do, gene therapy could be a way to get the 30% that fisetin does not reach, the 50% that curcurmin does not reach, or the numerous kinds of cytotypes and tissues that any known senolytic might not reach the cytoplasm of (cartilidge, eye lenses, osteocytes, other nonvascularized tissues).

Curcurmin and fisetin are published senolytics; could curcurmin as well as fisetin molecules with an antibody alerting moeity or tail, attached with: an enzyme endogenous to the cytoplasm that divides the curcurmin or fisetin from the immune system alerting moeity, which then travels to the outer surface of the exterior cytomembrane, which alerts the immune system to terminate the cyte that the senolytic has already localized and concentrated at. That only works if fisetin, curcurmin, andother senolytics actually localize to deleterious cytes. If they just go to allcytes, but only terminate deleterious ones, then a different technology would be the thing to make. If senolytics do localize and concentrate at deleterious cytes then putting immunoactivators on them would cause them to be even more senolytic as the immunocytes seek them out.



wellness technology: somehow leukocytes, macrophages and WBCs notice they are more effective at being an active and beneficial immune system when they travel past the capillary epithelia to actual cytotypes that provide a utility definition to a tissue (chondrocytes, pneumocytes, cardiocytes, dermatocytes, beneficial only immune responses to neurons, glia, mesentary, hepatocytes) to have a curative beneficial effect; that is they make their way past the epithelia to reach pneumocytes to engulf pneumocytes that have viruses and cure pneumonia when they do that. So, is there a chemical peptide or protein that causes luekocyctes and other immunocytes to move past, or between, epithelial cytes twice as often, twice as fast, or even travel preferntially along tissue cytes and omit a travel path that is along epithelial lined passgaeways like capillaries? Those would be drugs that multiply the effectiveness of the immune system at interacting with and vanquishing infections. Kindof like the utility of antibiotics, it could be possible to terminate twice as many infected cytes orinvasive organismsevery 24 hours, rapidifying recovery from illness and improving wellbeing.