Fisetin, a senolytic, is $22 per 10g on ebay, so creating variations on fisetin that are just as affordable or even more affordable could benefit even more people;
Aspartame: $40.96/Kg (ebay) is much like a two mer (unit) peptide, noting Pro-Gly favors transport to the brain, it is possible there are numerous two mer peptides, among 400 (20 amino acids times 20) variations, that localize at a variety of particular
tissues; It is possible that attaching these two mer peptides to fisetin or another even a more affordable molecule could create really affordable, perhaps even greater potency per milligram senolytics with beneficial effects at numerous tissues. That
also benefits longevity medicine worldwide.

Noting fisetin, which wikipedia mentions is sometimes called “5-Deoxyquercetin” is a phenol, it is possible other phenols are senolytics, a chlorinated phenol, possibly a variant on trichlorophenol or could be a senolytic that is 10 or 100 times
more potent per mg, thus making a fisetin equivalent dose go to $2.20/10g or even $.22 per 10 grams; at an approximate 500mg daily senolytic fisetin equivalent dose (although it is possible it is actually 6 grams every 24 hours if the mouse compensation
factor is ignored) that 500 mg is 11 cents a day (10 times potency) or possibly 1.1 cents a day (100 times potency).

Noting that quercetin is also a senolytic and has been published as being effective when combined with dasatinib the name version of fisetin that is Deoxyquercetin suggests the possibility of screening a library of the starting quercetin molecule could
find molecular variants that have longevity and healthspan benefits; chloro and other halogenated quercetins, possibly where the halogen replaces the oxygen at the body of the mid-molecule carbon cycle could do something, it could be the distal parts of
the molecule could have more effect (quercetin omits one -OH, so if fisetin is thought to be even more effective than quercetin then a halogen like Cl where the OH difference between fisetin and quercetin is could increase effectiveness further); Or,
noting ethynylization makes estrogen and progesterone go from hundreds of milligrams to hundreds of micrograms to be an effective dose it is possible an ethynyl version of fisetin or quercetin, where one of the-OH is swapped out with an ethynyl could
cause a senolytic variation on fisetin or quercetin that has 10 times, 100 times or even 1000 times less mg (or mcg) to be an effective senolytic dose and might localize at different tissues. If the ethynyl actually gets it to 1/1000 producing a few
hundred or tens mcg dose then a longevity and healthspan increasing dose of senolytics could be less than 1/10 of a cent to make, and noting fisetin on ebay is $22/10g something 1000 times effectiveness is near 1/10 of a cent per dose, also that is just
3.2 cents for a month long treatment or 1.6 cents for a 14 day treatment that I think I read about. That affordability benefits longevity of humans globally.

Fisetin dose and treatment length variation, “Fisetin turned out surprisingly to be superior to other currently known senolytic compounds. The study concluded it would induce apoptosis (cell death) in 25-50% of senescent cells. The dose which the
researchers used was 500 mg per day for five days for a 132lb / 60kg person so the dose needs to be adjusted to the individual persons weight.” so perhaps 700 mg a day for 14 days; also “Mayo human trials of fisetin. Dosage is 20 mg/kg/day for 2
consecutive days.” is 1.4 grams per day for two days, so possibly take 700 mg until 2.8 grams remain, then use the Mayo study dose for 48 hours. Also, Mayo Clinic: “100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol” is 7 grams per 24
hours. Phosal is Phosphatidylcholine Contents 25-75% with: Medium-Chain Triglycerides Sunflower Oil Safflower Oil Propylene Glycol; piperine may amplify fisetin potency: “It is claimed that taking 10 mg of BioPerine, a supplement that is reputed to
magnify the effects and potency of flavenoids and other supplements, along with a dose of Fisetin will greatly increase its bio-availability.”, “In our last session of taking a massive dose (5 g) of Fisetin, my wife and I took 10 mg of BioPerine with
each of ten 500 mg doses of Fisetin. This did seem to produce some magnifying effect, because I experienced a mild side effect (vertigo) that I had not experienced with a previous large Fisetin dose.”

fisetin with DHA: https://www.fightaging.org/archives/2018/10/animal-data-shows-fisetin-to-be-a-surprisingly-effective-senolytic/ “The combination of the two agents was found to have a strong synergistic effect on inflammation. Effective ratios
include without limitation those where fisetin is provided at a concentration of at least 5 μM, and where the ratio of DHA to fisetin may be at least about 1:2, 1:5, 1:10 or more". My add - is it synergy or fish oil increasing bioavailability?”
so 600 mg of fisetin would go with 3 grams of DHA, which could be beneficial as a lipid medium, 3 grams of DHA is about 30 fish oil capsules at the 10 times as much DHA as fisetin. The 2 days, or perhaps more at 1.4 grams of fisetin a day is again
about 3 Grams DHA at a two to one DHA fisetin ratio.

Oral fisetin is much more optimal as a longevity technology because oral is convenient, notably though, “It has been shown that the fisetin nanoemulsion injected intravenously showed no significant difference in systemic exposure compared to free
fisetin in mice, but when given intraperitoneally as compared to free fisetin, a 24-fold increase in the relative bioavailability of fisetin was found.”

piperine could heighten phenibut effectiveness and metformin effectiveness and antipsychotic effectiveness: “refer you to https://www.isotrope.com/bioperine/ . It says that: "P-glycoprotein is a protein the body uses to break down exogenous compounds
found in the body. This protein inhibits the action of many medications, and also regulates the degree to which certain nutrients are absorbed by the body. This protein actively controls the permeability of the blood-brain barrier, which directly impacts
the overall effects seen by many compounds such as curcumin—the active compound found in Turmeric. Piperine inhibits the action of this protein."

Perhaps piperine effects the permeability of the bodywide vascular epithelium as well, causing greater drug activity at numerous tissues and organs simultaneously. Fisetin dose frequency and plasma half life could benefit from a novel molecular form that
is nonreacted at the liver, fisetin’s plasma half life is described at a paper as being a quarter hour, at 233 mg/Kg in mice, although it is possible the mouse adjustment factor also applies to plasma half life, so that would make a human plasma half
life of 3 hours, which suggests 4 times a day daytime dosing. Then again the mouse compensation factor could just be some amount based on blood volume and liver volume, which I am not aware of.

I do not remember the moieties but I perceive that I have read about things that cause nonreactivity to liver enzymes at chemicals and drugs that could be made a part of senolytic molecules, Tyrosine sulfate is excreted through urine and, from what I
read is without hepatic metabolism. I have no idea what attaching fisetin or dasatinib to a sulfate moeity would do; It is possible that just attaching fisetin to a molecule that has a few hundred hour plasma half life (although with all those -OHs on it
it seems likely liver enzymes would modify those -OH even if one side of the molecule had some 200 hour plasma half life chemical like pimavanserin (an antipsychotic I am on) or a group like a sulfate that makes things like amino acids nonmetabolized;
another plasma half life benefitting version: the Mayo clinic liposome version of fisetin, lengthy circulation with perhaps gradual liposomal bag coming apart and gradual release or also liposomal migration past the vascular epithelia to actual tissue
cytes, skipping repeated hepatic passes (and metabolism) through the circulatory system.

Fisetin dose and plasma half life could benefit from that as plasma half life after IV administration is described at a paper as being a quarter hour, at 233 mg/Kg in mice, although it is possible the mouse adjustment factor also applies to plasma half
life, so that would make a human plasma half life of 3 hours, which suggests 4 times a day daytime dosing. Then again the mouse’ interval equivalent compensation factor could just be some different amount based on blood volume and liver volume and
amount of available liver enzymes, which I am not aware of.


Noting autophagy at cytes and organelles is there such a thing as autophagy of nonorganelle, possibly even nonprotein cytoplasm goop? I perceive at dermatocytes this is things like hyalonuric acid, so if hyalonuric acid has disintegration products then
cycling it to get fresh goop could be beneficial, also it is my perception that the volume of cytogoop is large compared to the size of lysosomes so there might be a non lysosomal goop improvement mechanism at phenotypically young cytes, also what of
cytogoop refreshingness at neurons?

Longevity technology: Some organisms like bacteria and possibly fungi like athlete’s foot fungi and yeast produce protein-lytic enzymes called proteases, it is possible that cytotransport of proteases to senolytic opportunities could cause sufficient
dissolving of things at the cytoplasm like organelles to cause organism benefitting apoptosis. To quantify the effect at huamns and human tissue: note the number and ratio of nonoptimal cytes at things like surface dermis or vaginal or even cheek dermis;
then have an antibiotic susceptible protease producing organism infect the tissue, which likely seems to then exude plasma like fluid and be gooey, then enumerate the percentage increase in young phenotype cytes after some number of hours of infection
and then do organism infection termination with antibiotics; if the proteases are senolytic then although they are infected the remaining healing cytes would be youthful phenotype and be the cytotype that lives, and the tissue restored to youthful
phenotype.
Also, if this is accomplished without bacteria, just using calibrated repeatable laser ablation of mouse dermal tissue, this would be a way to screen a library of hundreds or even thousands of proteases and other enzymes to find some that are medically
actual senolytics, also, at tissue culture it would be possible to see if the dermal senolytics also had senolytic capability at completely different tissue like those found at depth in the body.
I think I read that some viruses code for proteases so the viruses can make tissue gooey, spreading the virus; engineering those viruses, or possibly breeding them to make senolytic proteases or other enzymes could make an internal to the body produced
senolytic, possibly with some tissue localization, that has better coverage and puts less stress on the body than systemic or organ or tissue concentrated bacteria or fungi would.

Brain function friendly, cognition enhancing senolytics: I read there are about 30 different neurotransmitters, linking a senolytic molecule such as the comparatively few AMU dasatinib or fisetin to each of their neurotransmitters, or chemicals that
concentrate at that specific neuron-type creates 30 varieties of brain senolytics to quantitatively measure 30 different individual as well as combinable forms of induced youthful phenotype at. Describing this neuron-response-to-senolytics space is used
to produce cognitively beneficial and harmless youthful phenotype at the brain; supporting this technology: I read a paper about dasatinib with quercetin where they measured the cognitive ability and nimbleness of mice who received the dasatinib with
quercetin combination, the mice improved their cognitive ability as well as their nimbleness. it is possible that measuring the 30 different kinds of neurotransmitter-neurons as well as things like glia and astrocytes will increase cognitive, longevity,
healthspan, wellness and youthful phenotype benefits while reducing risk. Noting published papers on the correlation of mental capability with longevity it is possible brain active senolytics could be even more effective than body senolytics at causing
increased longevity.


Even at body surface senolytics it is possible that lung wellness and function could be heightened with a senolytic protease or other enzyme producing virus. While different than an immunization a one injection virus based tissue localized proteolytic
senolytic would be beneficial.

longevity technology: If an efflux transport channel at a cyte is blocked with a drug, and a bioactive chemical that would usually be effluxed is possibly also stimulated to be at a higher amount at the cytoplasm with a different drug (or a molecularly
modelled new drug that does both things simultaneously), does that bioactive chemical then build up at the cytoplasm: that could cause a cytotype localized senolytic drug effect if the decreased efflux and thus heightened cytoplasm amount that is
increased is a protease or some apoptosis enzyme.
Longevity drug:The efflux blocker with stimulation of greater cytoplasm amount technology could also be used to heighten the concentration of nonsenolytic endogenously produced longevity chemicals like autophagy stimulators, heat shock proteins,
optimized histone things like methylators or acetylators,

GSK: Proteases after the application of dermal beauty treatments like lasers or chemical peels could cause a senolytic-effect cytokine, and chemokine reduction, and matrix protein optimization activity and a restoration of dermal tissue to youthful
phenotype; proteases that function like senolytics, as well as other published senolytics topically or even orally could possibly cause an all youthful cyte population at the beauty treatment area which causes more rapid higher quality healing at both
beauty treatments and surgical sites, possibly even reducing scarring; sutures with senolytic chemicals, possibly including proteases could be quantitatively measured to find out if they work more optimally.

Senolytics that affect bone marrow could be beneficial, “The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after H2O2 sublethal oxidative DNA
damage and in their PARP gene expression.[13] These findings suggest that elevated PARP gene expression contributes to the longevity of centenarians, consistent with the DNA damage theory of aging.”,

One senolytic that works on bone marrow is tetramethylpyrazine, a food flavoring, where 80 ml of 10% solution was near $33:
Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti-inflammatory and angiogenic environment in aging mice”, “Our findings revealed that local delivery of TMP eliminates
the senescent phenotype of LepR+ MSCs via epigenetically modulating angiogenic environment in aging mice.”
Non oral dose of tetramethylpyrazine at bone marrow senolytic, “divided into different concentrations of TMP‐treated groups (0, 1, 10, 100, 1000 μg/kg)” 1 mg per Kg, so as an oral human rather than mouse drug it is plausible to multiply the amount
of drug by 40 imagining that an oral drug is 40 times less physiologically less there, then divide by 60/5, the mouse compensation factor to produce a senolytic dose of 233.33 mg for a 70 Kg human. If oral tetramethylpyrazine is 1/100th the activity of
IV then it is 583.33 mg a dose. At food grade TMP, 80 grams of 10% solution for near $33 online, the 8 grams of TMP would treat a human for 16 days at 500 mg a day.
Perhaps I will find out what the circadian, multi-sleep, what 24 hours means to a mouse metabolism effects on medication conversion are. Noting frequency of eating and sleeping during 24 hours it is possible the mouse is being dosed once every 7 or 11
sleep/eat cycles, so does that have a compensation or technology effect on a human taking a drug, like, is a senolytic dose every 24 hours at a mouse like a senolytic dose once every 7 or 11 days at a human? I do not know.
tetramethylpyrazine is on alibaba.
They could screen a library of tetramethylpyrazine variants like butyl rather than methyl versions, halogenated versions, as well as C=O instead of C-OH versions and C-EtOH versions and calcium phosphate versions. It is possible they already are doing
these things. Bisphosphonate, a drug, could be a moeity that transports tetramethylpryazine to osteoareas, “bisphosphonate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The
remainder has a very high affinity for bone tissue, and is rapidly adsorbed onto the bone surface. Once bisphosphonates are in bone, they have a very long elimination half-life that can exceed ten years.”
one article says that a particular, or perhaps some, senolytics function by unblocking paused apoptosis, so they could see if making mice with extra copies of apoptosis genes or a more promoting promoter sequences at those genes causes the mice to live
longer with longer healthspan; it is possible this gene therapy or possible germline modification could effect many more tissues as a senolytic than some other approaches. It is possible RNA drugs or siRNA drugs, perhaps transported with liposomes could
amplify or activate the apoptosis genes to be another senolytic drug, although based on the material online I have read, germline modification and gene therapy would provide more optimal longevity and wellness effects at humans.
One graphic https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12344 suggests about 196 different genes change their expression at young well cytes compared with cytes where the organism would benefit from apoptosis. The cytes where the organism
would benefit from their apoptosis, to my perception of the paper, actually have more gene expression, so likely more protein production, than the well cytes.
If there is a chemical that changes the shape or quantity of lysosomes that do apoptosis, or even a mitochondrial apoptosis effector that chemical could be a new senolytic longevity and wellness drug; It is possible NMN, or even ribose linked to a mostly
harmless chemotherapeutic drug, like possibly the chemotherapy molecule with the least side effects could be a senolytic from a mitochondrial concentration and membrane passing effect.
They could identify biological chemicals unique or at different concentrations to create new human longevity drugs, among the possibilities are something like electrophoresis of blenderized quahogs then seeing if the biological chemical electrophoresis
bands cause yeast or ce elegans to live longer, then if they do engineer bacteria to make those chemicals, if they are proteins or peptides at sufficient quantities to test them on mice and humans; “The quahog clam (Arctica islandica) is exceptionally
long-lived, with a maximum recorded age of 507 years, the longest of any animal.” The mitochondrial genome of the quahog has been sequenced and, to my perception, has some novel things. Similarly they could identify the chemicals in blenderized
tardigrades to find out if any make yeast as well as other organisms live longer. Also, among a sample of perhaps less than 100-300 tested rockfish the shortracker rockfish has lived 200 years so rockfish tissue could be blenderized, electrophoresized,
and have its effects measured on yeast, c elegans, mice. I perceive I read some drosophila live 4 months while others live 2 months, blenderizing, electrophoresis, and longevity effects from screening the library of isolated biological chemicals at yeast
and drosophila could find new or novel longevity chemicals at the drosophila that live twice as long, particularly compared with the other drosophila.

Killifish live 1-2 years, ebay: $9.99 for 30 eggs, there is another fish that lives 6 months but I could not find it again on the web. So these might be a thing I could test new longevity drugs on with n>=8 to get a p value. like compare NMN soaked food
to ribose with nicotinomide soaked food with deprenyl with metformin with senolytics, as well as AEDG with thymosin, as well as other, chemicals with even more utility,possibly even LKM512 as well as C60 olive oil, both of which have greater than 90%
published greater longevity at lab mammal effects, also then make a web page. So 40 eggs, or 60 eggs assuming some do not hatch for $19.98.
https://themysteriousworld.com/top-10-shortest-living-animals-in-the-world/ Drosophila live about 60 days and have numerous publications; Carolina Biological Supply has $59 and $90 kits, $8.75 drosophila single culture versions also $9.25 edible material
drosophila longevity experiment supplies at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582515/ ; Also I could see if new things like halogenated versions of various published longevity drugs have different effects like chlorinated metformin,
halogenated rapamycin, chlorinated senolytics like fisetin, others, if the difference at the fish or drosophila is more than 40% better (14% longer than unmedicated fish or drosophila) than the usual metformin amount, or as well as the usual senolytic
longevity increase then I could risk making and taking human doses of chlorinated metformin, halogenated senolytics, or also other halogenated longevity drugs.
Well baby supplement, Hint of longevity technology or longevity genetics, “No enzymatic mechanism of tyrosine sulfate desulfation is known to exist. By knock-out of TPST genes in mice, it may be observed that tyrosine sulfation has effects on the
growth of the mice, such as body weight, fecundity, and postnatal viability.” I perceive body weight, fecundity are similar to longevity drugs and biological forms where things like metformin or castration affects gonads and weight and can be used to
delay puberty, and that puberty above the 50th percentile of delay might be linked to greater human longevity (I perceive something like 90th percentile or higher of puberty delay has stronger correlation with longevity than upper half of delay (50th
percentile) as to when puberty occurs), so tyrosine sulfate promoting or modifying drugs could be created and tested as to longevity effects, if more is better then “universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS)” could be a
longevity drug, also possibly large doses of glutathione; Also as regards to sulfonated tyrosine effecting what wikipedia describes as postnatal viability; that suggests a possible well fetus well baby medication or supplement. My perception is that
from the researchers studying mice the research suggests: normal or perhaps more tyrosine sulfonation is beneficial, if it is more then maternal or even baby supplementation could benefit babies, perhaps even direct consumption of sulfated tyrosine,
tyrosine, or some harmless possibly GRAS chemical that increases sulfation of chemicals at the liver would be beneficial, also baby mice that cannot make tyrosine sulfate get pulmonary disease; Wikipedia says about where tyrosine sulfate gets its sulfate,
“a transfer of sulfate from the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS)”, or perhaps big doses of glutathione which has publications suggesting it is beneficial, these could be quantified as to benefits to fetuses,
babies, and what wikipedia means when it says “postnatal viability”. Also, any human SNP variations in tyrosine sulfation genetics could be correlated to baby wellness as well as post pubertal wellness, personality, and other psychological metrics
noting that tyrosine supplementation enhances mood and alertness, excess sulfation could affect personality as well as baby wellness.
“Magnesium [sulfate] administration attenuated the increased BBB permeability defect and caused a reduction in brain edema formation in our rat model of intraperitoneal sepsis”, the magnesium sulfate made the blood brain barrier about 4 times less
permeable at the unwell rats. Alternatively, some chemical or protein isolatable from sepsis, while as an isolated chemical product is absent the unwellness of sepsis might make the blood brain barrier 4 times more permeable, possibly on a 24 or 48 hour
basis, to permit the passage of beneficial drugs, like longevity wellness healthspan heightening drugs as well as beneficial gene therapy.
Causing an organ to tissue barrier to be temporarily permeable could have medical value:Similarly it is possible the gonad-blood barrier or even the placenta could be beneficially addressed with fertility or menstrual cycle wellness drugs, or at the
placenta heightened benefit from things like omega-3 lipids or other things that benefit a fetus
It might be possible to create a drug that causes a narrow 5 minute period of blood brain barrier, gonad brain barrier, or placenta as barrier activity window for administering a beneficial drug. Attaching a moeity that the liver is really avid about
chemically modifying could do it, Also it seems kind of primitive, but a person could be immunized against a cytomembrane transport molecule that is rare and does not occur endogenously, then a blood brain barrier permeability causing drug, like some
bacterial products or piperine is attached to the antigen, the antibodies might be able to clean it up out of the circulation in less than 3 minutes, noting that there is actually an immunization against cocaine which pre-empts the mental effects of
cocaine just from durably circulating antibodies. I have no idea how this could possibly work as 100-300 mg of cocaine seems like it would require 1-3 grams or much more of the much larger AMU antibody to be circulating, and glom onto the cocaine before
it reached the brain; technologically though it suggests it is possible to have a 3 minute window of high blood brain barrier, blood gonad barrier, or placenta high permeability.
Also, variations of the blood brain barrier, possibly correlatable at human genetic SNPs and then genetically modifiable at laboratory mammals to test hypotheses about things like: at a group of well persons, such as supercentenarians, with 99th
percentile of blood brain barrier form both among the supercentenarians which would be compared with the population of children’s blood brain barrier permeability;
Noting that a combination of epithalon which is similar to a pineal product and thymosin causes humans to be 4 times less likely to be nonalive after 6 years and that the thymus and pineal are absent being filtered with the blood brain barrier it is
possible that the brain or cerbrospinal fluid secretion tissues produce other chemicals that would benefit the body. The pituitary has a blood brain barrier filter between it and the circulatory system, I am without any idea what would happen without a
blood brain barrier filtration of exported pituitary chemicals.
Notably however measuring the amount of permeability of the blood brain barrier at supercentenarians could come up with data that supercentenarians have 90th percentile or higher of blood brain barrier minimal permeability, which suggests a genetic basis
of supercentenarian physiology that can be made available to everyone with blood brain barrier permeability reducing drugs as well as gene therapy and also germline modification.
Noting measurements of supercentenarians, a published paper says magnesium sulfate causes the blood brain barrier to be 4 times less permeable, and if blood brain barrier permeability has a quantified beneficial effect on longevity, wellness, and
healthspan then magnesium sulfate supplementation could be a longevity drug. Also as a possibly longevity wellness parameter what is the permeability of the blood brain barrier at children and teenagers, it is possible that permeability is more optimal for people post-teens.
Screening a cerebrospinal fluid library to find longevity molecules: compare and find uniques among the different molecules and concentrations of a screenable library of same, shared, or chronological age unique molecules at teens and children with those
of supercentenarians: are there different chemicals or different amounts? Does chemical, supplement, or drug administration, gene therapy, or genetic SNP variation increase longevity, wellness, and cognitive function when supercentenarian CSF is
modified to be like that of children?
It could benefit babies to have blood pressure in the 1th to 32th percentile, (just imagining that 1 standard deviation less of osmotic and blood pressure stress could benefit babies; also do babies experiencing some emotions or even thoughts then have
measurable blood pressure “skyscrapers”? If they do is there a nootropic wellness promoting blood pressure reducer; the sweet sugar-OH mannitol reduces intercranial and ocular pressure, tastes good, and might be harmless as well, Although I perceive
babies get lots of loving touch and often experience music it is possible more of these things could benefit babies; it is also possible a laser based blood pressure monitor could measure the blood pressure of babies, if it happens to matter, and alert
the parents, again, if it matters), “the blood–brain barrier (BBB) was still immature in newborns. This was due to an error in methodology (the osmotic pressure was too high and the delicate embryonal capillary vessels were partially damaged). It was
later shown in experiments with a reduced volume of the injected liquids that the markers under investigation could not pass the BBB”

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