Read a book on how to do babysitting,
then advertise to talk to a babysitter, and ask if you can do her overflow or when she is not available, possibly 7-3 during school year. Pay her a comission for every hour of babysitting that occurs, and have her collect the money and give it to her favorite charity, with her reserving her comission out of the earnings.
Longevity technology:
fisetin is a senolytic. tyrosine sulfate is not metabolized by the liver. It is possible although unknown to me that fisetin sulfate could possibly be senolytically active while having a long sustained plasma half life as, like tyrosine sulfate it would be gradually excreted as urine. I do not know if sulfates pass through exterior cytomembranes or pass epithelial cytes, it is possible that putting an enzymatically dividable linker molecule like a ribose, a two mer (unit) peptide or even a acetyl link like the one at sucrose that goes between the dextrose and fructose between the sulfate part of the molecule and the fisetin part of the molecule could cause much greater plasma half life, but be able to have the fisetin separate to be an active senolytic at the cytoplasm because of enzymes endogenous to the cyte’s cytoplasm; as a possible localization opportunity it is possible that some kinds of cytes have very different endogenous enzyme concentrations or types than other cytotypes, so the long plasma halflife version of fisetin would cause fisetin sulfate to soak in all over the body with a multi hour or even multi day plasma half life and only divide from its sulfate at the linker site at a particular kind of cyte with the right enzyme, perhaps a deacetylase or an aminoacidase. Or an opportunity: if the linker molecule is ribose, NR, NMN or something like coenzyme Q10, then it is possible the amount of enzymatic activity at the cyte will be directly related to the number and activity of the mitochondria at that cyte: localizing fisetin to high mitochondrial number or also high mitochondrial metabolic output could concentrate a senolytic at a particularly active tissue, localizing the senolytic effect
fisetin palmitate or dasatinib palmitate as a super long plasma half life senolytic, palmitate depot drugs last, I perceive as long as 3 or 6 months from one injection, so compared with what might be a 1 hour human plasma half life at fisetin the fisetin palmitate would be at active drug strength for 4320 hours, so 3 orders of magnitude longer lasting senolytic activity. Palmitates possibly just attaches a C16cooh to some part of the fisetin or dasatinib (dasatinib actually has an ethyl with an -oh on the distal part that might be replaceable with a C16cooh as kind of similar from my uninformed perspective) or another senolytic, the fisetin might still work as quercetin looks like fisetin and is one -OH different and some other -OHs are like a different angle of para on a benzene, and quercetin kind of works as a senolytic, noting dasatinib with quercetin published effective senolytics.
longevity technology:
So, noting magnesium sulfate (epsom salt) makes the blood brain four times less permeable should I take it because phenylethylamine blood pressure effect raises my blood pressure and because pressurized osmotics at the blood brain barrier? I could even just take it the day of phenylethylamine
It would be nifty to find out if magnesium sulfate had an effect on placenta permeability, if it does it could be a mass production veterinary drug that possibly benefits mammal fetuses, imaginably 1-2 per 100 mammals. a thing from wikipedia supports magnesium sulfate as a possible well pregnancy drug, “Magnesium sulfate is effective in decreasing the risk that pre-eclampsia progresses to eclampsia.[11] IV magnesium sulfate is used to prevent and treat seizures of eclampsia. It reduces the systolic blood pressure but doesn't alter the diastolic blood pressure, so the blood perfusion to the fetus isn't compromised.”
The four times less permeability at the blood brain barrier along with the blood pressure reduction makes me think that magnesium sulfate (epsom salts) could reduce the risks of phenylethylamine, but, this onlinbe thing says it is only 2 units, “people receiving a median of 368 milligrams (mg) of magnesium a day for an average of three months had overall reductions in systolic blood pressure of 2.00 millimeters of mercury (mm Hg) and diastolic blood pressure of 1.78 mm Hg.”
Dose: “intramuscularly (6 g loading dose followed by 2 g/h)” oral constipation dose, “2 to 4 level teaspoons dissolved in 8 ounces water orally
-Repeat dose in 4 hours if needed.
Maximum dose: 2 doses per day”
a million cytes processed in a few hours (2015 AD), “The "µ" stands for the microcapillary glass slide that holds the protein samples. The slide is roughly the size and thickness of a penny, yet in that space a million capillary tubes are arrayed like straws, open on the top and bottom.
The power of µSCALE is how it enables researchers to build upon current biochemical techniques to run a million protein experiments simultaneously, then extract and further analyze the most promising results.”, “The slide bearing these million yeast or bacteria, and the protein variants they produce, is inserted into the µSCALE device. A software-controlled microscope peers into each capillary and takes images of the biochemical reaction occurring therein.”
a different system does 100k yeast per second, or 10 seconds to process one million yeast, “To show the system’s utility, we demonstrate high-throughput image-based screening of budding yeast and rare breast cancer cells in blood with an unprecedented throughput of 100,000 particles/s” https://www.pnas.org/content/109/29/11630
when using a million yeast to see if any of the protein parts of something like a 200 year old rockfish’ tissue causes yeast to live longer it is possible that the
It is possible that yeast engineered to produce more fluorescent protein each 24 hours could be detected as to their lifespan with the very oldest yeast producing the most fluorescence, then you would just coat a freeze fractured, possibly freeze dried micropowder of a 200 year old rockfish’ tissue or a freeze dried freeze fractured sample of filtrate from seawater with the fluorescent yeast, and wherever the camera detected a one per million yeast longevity event the eentsy portion of freeze dried freeze fractured tissue the yeast was on could be isolated, and the chemicals and proteins in it characterized to find proteins, peptides or other chemicals that caused the one per million yeast longevity event. It is possible that if 11 to 100 yeast grow on each microfragment of the biological library of rockfish tissue or ocean water filtrate then the yeast could be isolated while alive and measured as to things like the mRNA or other cytoprocesses that caused them to be unusually long lived. The blob of longevity chemical releasing tissue could also be dug out of the array to find and show the organism or sample that caused the longevity effect at the yeast.
Numerous longevity technologies at the notebooks make use of screening a library for new longevity producing molecules, noting the 1 million yeast screened per 10 seconds a camera system that finds and isolates the most fluorescent, from having lived the longest, yeast seems possible
.
Longevity drugs:
Fifty‐three lifespan experiments, involving 30 test agents, have been initiated in the first 11 years of the ITP. Significant effects on longevity, in one or both sexes, have been published for 6 of the tested agents: aspirin (Strong et al., 2008), nordihydroguaiaretic acid (NDGA) (Strong et al., 2008; Harrison et al., 2014), rapamycin (Harrison et al., 2009; Miller et al., 2011, 2014), acarbose (ACA) (Harrison et al., 2014), methylene blue (Harrison et al., 2014), and 17‐α‐estradiol (17aE2) (Harrison et al., 2014).
17‐α‐estradiol (17aE2)
Beginning at 10 months of age, male and female mice were fed chow containing 17aE2 at a concentration of 14.4 ppm (17aE2). As shown in Table 1 and Figure 1, median lifespan increased 19% in male mice, calculated from data pooled from the three sites (P < 0.001). The effects of 17aE2 were significant at all three sites, at P < 0.003, with increases in median survival of 26%, 9%, and 23% at TJL, UM, and UT (Fig. S1, Supporting information). The age at which 90% of the mice had died increased on average by 12% (21%, 8%, and 8% at the three sites;
dose: 14 ppm in mouse food, or .014 Grams per Kg of food, it is unknown how much food mice eat every 24 hours. It is possible they eat 5g of food every 24 hours which would be a human dose of 2333 mouse measl per human per day, or 11.665 Kg of food equivalent aE2 per human, or 163.3 mg of 17aE2 per human per day, or with mouse compensation number, 13.6 mg aE2 per day
17aE2 is at alibaba.com
Rapamycin with metformin: Males given Met/Rapa had a 23% increase in median longevity
food: 14 ppm rapamycin, 1000 ppm metformin
163.3 mg of rapamycin per day for a human, with mouse compensation number, 13.6 mg per day at a 70 kg human.
1000 mg per kg, 30 gram mouse, 5 grams of food every 24 hours is 11.66 grams of metformin per human, with mouse compensation number, .972 grams of metformin per day per human.
NDGA: Nordihydroguaiaretic acid (NDGA)
In a previous study, we tested the effects of NDGA on survival of male and female UM‐HET3 mice at a dose of 2500 ppm and reported that median lifespan was increased in males by 12%, with no benefit in female mice (Strong et al., 2008). In the earlier study, 9% of male control mice were alive at the joint 90th percentile age, compared with 13% of NDGA‐treated males (P = 0.12).
Acarbose (ACA)
Beginning at 16 months of age, mice were fed chow containing 1000 ppm ACA. The results are shown in Figure 6 and Table 2 with site‐specific statistics in Table S3 (Supporting information). Pooling the data across sites, there was a significant increase in survival for male mice treated with ACA, with a 6% increase in median lifespan and a significant 12% increase in maximal lifespan
a peptide: https://interestingengineering.com/12-innovations-that-could-make-reverse-aging-a-reality “testing pNaKtide, a synthetic peptide that could further reduce risks of illness and the effects of aging.”, “The study saw researchers successfully reverse the biological state of the brain in mice aged 12 months and 18 months. The test mice were treated with THC in small, non-intoxicating doses for a period of four weeks. They were noted as out-performing the control group who had been given a placebo, and were shown to have similar cognitive performance to younger mice. This could mean that non-intoxicating THC treatments might allow older humans to regain youthful levels of cognition.”
Two days before July 27th, 2019
A drug that makes people more big five psychology test: conscientious (kind of like myers briggs J) could be a drug that causes greater success are various kinds of things, a successtropic. Some social efforts could be replaced by prescribing mentally well people in the bottom 30th percentile of doing well successtropics to voluntarily take. One possibility is looking at the fMRI and positron emission tomography of people at the 90th percentile of doing well and seeing if they have more or different activity at various locations and many different kinds of neurons and neurotransmitters. It could be brain system activation thing as well though, so perhaps computer software or virtual reality could do it.
Acarbose is published as causing 9 or 10% longer lifespan in mice at 1 part per 1000 in mouse food, wikipedia says that it is produced as several versions at one pill, “WHere was the structure for acarbose sourced? I think the stereocenters might be wrong. I have a feeling it was sourced on PubChem. There are MULTIPLE acarbose structures on PubChem. See here. The think the correct stereo is as shown here oChemSpider. However, this is my opinion and it needs confirming. Help.--ChemSpiderMan (talk) 00:30, 25 January 2008 (UTC)
Yes, I used PubChem as a source at the time. I'm not sure of the stereochemistry; as you just said, help :) Fvasconcellos (t·c) 00:57, 25 January 2008 (UTC)
The information from Bayer is here it seems its sold as a mixture of anomers” So perhaps just one of the versions is more active at causing longevity.
It was pleasant to find out that liposomes transport things inside them to the lympathic system, where they have more biological activity that going to the liver through a vein, “Lipid-based nanoparticles
(formulation-derived)
Administration of a single capsule of long-chain lipid can stimulate significant lymphatic transport of drugs.
- Solid lipid nanoparticles
- Self-nanoemulsifying drug delivery systems
- Emulsion
- Liposomes
- Effective carriers for drugs
- Stimulators of chylomicron production
The effect of the formulation on drug absorption and lymphatic transport is less clear.
“
liposomes like senolytics might be makeable with phosphatidyl choline and or as well as lecithin at $24.98 magnasonic ultrasonic cleaners on ebay. could up dose of dasatibin, rapamycin, acarbose, others. Some use 35 kHz to make liposomes, magnasonic is 42 kHz
There is something called phosol Some phosol might be 25-75% phosphatidyl choline, with MCT (like coconut oil), sunflower oil, safflower oil, propylene glycol. Mayo clinic fisetin study was “For oral administration of fisetin, mice (“At 85-weeks of age (>20 mth), male and female mice were administered a diet containing 500 ppm (500 mg/kg) fisetin[fisetine mice live to 125 weeks, non-fisetin live 105-110 weeks without fisetin) were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/ at humans that is 100 mg *70, or 7 grams per dose, or using the mouse compensation number, 583 mg per human dose.
Also as to length of treatment, the Mayo clinic dose is two consecutive days, but this paper has mice going from 6 to 14 weeks, with two two week doses during that time (6-8 weeks and 12-14 weeks) and greater than halving their messed up cytes from the two groups of two weeks of treatment during that that 8 week interval; https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext The mice get 500 mg/Kg, 35G/24 hours or with mouse compensation number 2.91 g/24 hours, so at a human for 2 weeks that would be 14*2.91 or about 41 grams, or 82 grams for the two 2 week dosage events. A different procedure at the same paper has 100mg/Kg for five days reducing markers of nonoptimality going to 1/3 of 1/5 of the untreated mice and having values similar to those of young mice. With mouse compensation this goes from 7g a day for 5 days to 583.3 mg/24 hours for five days
I think phosphol was used at the Mayo clinic 1.4 G per day, 2 day with 10% ethanol. so ultrasonic liposomes with 75% phosphatidyl cholone and 5% ehtothol or 10% ehtanol might work. Make different versions of liposomes and then use microscope at the marine life center to verify they actually are liposomes.
This describes making liposomes with ultrasonics: https://www.quantumbalancing.com/liposomalC.htm
At ascorbic acid it says it goes from 19% absorbed to 93% absorbed with the liposomal effect.
Weird new fruit: An apple with lots of layers of skin at its interior, or a grape with many layers of skin: I perceive I have seen vegetable or fruits with interior versions of the same fruit in them. Apple polyphenols cause 10-12% greater longevity in c elegans and drosophila, and 43% reduction in human mortality at a correlation study, so a delicious fruit that was like 14 layers of outside skin could be a one fruit (like an apple) that has 14 times the longevity and wellness benefit from fruit polyphenols (like an apple); One way to make this taste more optimal is to increase the sweetness, wikipedia mentions a beneficial polyphenol, “ingested phlorizin is converted into phloretin” as well as “Phlorizin is a white to yellow crystalline solid with a melting point of 106–109 °C. It is of sweet taste”, so just breeding fruit (like apples) to have more phlorizin could make them taste better as well as possibly heighten wellness, although the benefits from eating apples. as published, are much less than those from concentrated apple phytochemicals. Still, 14-40 times more skin at polyphenol containing fruits from nesting layers from new bred varieties could have concentrate like effects from one fruit.
Also, with genetic engineering the apples could make sweetness peptides at the skin and cortex making it more delicious than regular fruits (like apples) “Treatment with apple polyphenols extended the life span of natural C. elegans by 12%.1 As with the previous experiment with apple polyphenols, activation of sirtuins’ calorie restriction-mimicking effects was evident.”, “apple polyphenols have been shown to extend by 10% the life span of the fruit fly, D. melanogaster, another commonly-used model of human biological processes and aging”, also “those who consumed the largest amounts of flavonoids (found in apples and other fruits) were shown in one study to have up to a 31% reduction in total mortality.9, 10 When intake of apples specifically was examined, that study showed as much as a 43% reduction in death from heart attacks specifically.”, “Animals fed apple polyphenols had up to a 17% reduction in the size of atherosclerotic lesions found in their arteries” https://www.lifeextension.com/magazine/2012/4/Apple-Polyphenols-Longevity/Page-01
Phlorizin reduces some glucose things “phloridzin inhibits glucose uptake by 52%” functioning sort of like metformin or acarbose, it causes mice and humans to be skinnier, and is cardiobeneficial
Apple polyphenols are available at ebay, $17.17 22.5 grams as 125 mg and 180 pak pills. one research dose, “adults were given 600 mg/day of apple polyphenols”
Making dimers with electric plasma, “Nonthermal dielectric barrier discharge (DBD) plasma-induced structural changes in dihydrochalcone phloridzin (1) resulted in the isolation of three new methylene-bridged dihydrochalcone dimers” So, does this work on a bunch of other polyphenols and glucosides (things with a glucose moiety) So perhaps plasma dimerized fisetin might be as or more effective than fisetin.
Million or hundred million sample mass screening of libraries of chemicals for longevity drugs: screen libraries of possible sources of new longevity drugs with libraries of chemicals from wild fungi, blenderized bugs that have been given cancer with radiation, other blenderized inertebrates, blenderized plant tumors and galls, filtered material from ocean water and freshwater; use the published million capillary tube microfluidic sample tester I read about and possibly the yeast enumerating cytoenumerator I read about that images 100,000 yeast per second of 6 million yeast per minute, 360 million yeast an hour.
To find the longest lived yeast, genetically engineer yeast to make more cumulative GFP (green fluorescent protein) or BFP (blue fluorescent protein) the longer the yeast live, then yeast that go through the imager and have the brightest fluorescence are the longest lived.
A microfluidic million yeast array, that has living colonies, part of which are sampled or characterized automatically for longevity, from utilizing fluorescence imaging, and have the rest of the yeast available and alive for culturing as well as array location findability to find the chemical that makes the yeast live longer are produced at a 1000 times 1000 grid, made from things like integrated circuit technology, laser ruling of a yeast nutrient gel, or microfluidic system fabrication technologies like that used to produce the million capillary array.
microfluidics or just floating a layer of material atop the array grid places things from the library being screened onto the gel; Lasers then energetically comminute half or a third of the array location’s unique library material. I have seen holographic diffraction gratings for lasers where something like a .5 mm beam is divided into many hundreds of bright dots at a patttern. With a more powerful laser, and a custom holographic diffraction grating filter, several hundred or even thousand little point beamlets can be produced. then with a powerful enough laser these beamlets are strong enough to pop open a plant tissue fragment, some fungal cytes, (sort of like laser disintegrating a surface), popping open a library fungi blob, or comminute just part, like a third of a marine filtrate organism. This is all done at the surface material lying on the nutrient gel, or just possibly the laser comminutes and pops a third of a library item just a few micrometers under the nutrient gel surface. The laser could also warm the array spot with the blob it has just comminuted 1/3 of, to get the chemicals in the comminated material to diffuse rapidly through the gel, so that when yeast grow on it’s surface the yeast will be affected by the diffusion of the chemicals from the popped cytes of the library. One benefit of a using a laser, raster scanned, or holographically microbeamed to pop library samples is that after the yeast colonies coating the upper side of the gel react to the comminuted diffusive material with greater longevity, a 2/3 remaining sample of the original library material can be scooped up to provide a sample of the organism or part of it, that causes the longevity effect. If you are screening a library of fungi, and the array item has a 70 times 70 micrometer bunch of hyphae under a micrometer of gel, and the laser comminutes and warm-diffuses a 20 times 20 micrometer area of the hyphae, if those fungal chemicals cause greater longevity then there is enough remaining hyphae to find out what, and which chemicals, caused the increased longevity at that array element location. Similarly for 90 times 90 plant tumor fragments with 20 times 20 areas of laser comminution and warmth based diffusion.
Along with lasers, zapping some of a sample and leaving enough to identifity what it is, when as a library item it causes greater longevity; other methods like freeze fracturing as well as autolysis of library tissues are other methods of modifying things at the library, on the array, to release their chemicals for the yeast to respond to as they grow.
Freeze fracturing or inducing autolysis (“The general method for making yeast extract for food products such as Vegemite and Marmite on a commercial scale is to add salt to a suspension of yeast, making the solution hypertonic, which leads to the cells' shrivelling up. This triggers autolysis, wherein the yeast's digestive enzymes break their own proteins down into simpler compounds, a process of self-destruction.”) notably where the autolysis chemical is harmless to yeast, possibly isotonic with dilution or addition of a buffer, produces items to be in the screened library (like the many organism ocean or feshwater filtrate, sonicated, possibly autolysed bug or plant, or fungi goop) produces availablized chemicals, notably cytoplasmic chemicals, that are then microfluidically moved or pumped onto the yeast nutrient gel array to make a diffusive gel layer, then a rinse of live yeast on that layer to grow colonies. A flourescent laser and camera (possibly raster scans or better) looks at the million colony array and finds the array items with the brightest GFP, then those chemicals that caused the greater longevity are looked up (the array has a numbered row column reticle), and those are items from the library that are things that can be genetically engineered into other organisms to make sufficient amounts to medicate c elegans and mice for further longevity studies.
There are different, I think better ways of mass screening libraries of longevity chemicals at my paper notes which are likely to be imaged and on this website.
Finding new variations on longevity chemicals and drugs with greater effectiveness: have microfluidics deliver the drug to a microreactor such as a microfluidic binomat, with 11 different sequential reactions based on catalytic, enzymatic, or reagent binomat pegs, and 100 to 10,000 base collector channels, resulting in 11 factorial different reactions the initial chemical experiences, producing 399 million different chemical variants. The microfluidics transport these to million location yeast arrays. So you put acarbose or rapamycin among many possible drugs or chemicals, as well as those from screened libraries in the top of the binomat, and have it react, or be catalyzed 1 to 11 times sequentially altogether with things like Co, lithium aluminum hydrate, trypsin, iodine metal, pepsin, hydroxylase, hydrogenase, cycle-opening (<=> —> \/\//) as well as others; notably if highly affordable reactants and catalysts are used at the binomat then the chemical production of those drug variants amongst the 399 million are particularly affordable to make and the chemical engineering could favor simpler scale-up and possibly STP reactions, resulting in less manufacturing cost. I have seen an image of a fluidic binomat online; also it is possible to use two or three binomats with 3 or 4 reactive, catalytic or enzymatic pegs each then feed the result of one binomat into another to make the 399 million variant 11 catalytic, enzyme, as well as reagent pegs. If the published 360 million yeast optically screened per hour technology is up to it then 3 billion chemical variants can be screened in 10 hours, at the billion item array of colonies, Also possible is the laser raster scan and camera to look for the most fluorescent yeast among one billion array items at planar array. At 6 micrometers diameter per yeast, then an array 31623 locations on a side is just 32 millimeters on a side where each array item contains 100 yeast per colony. A larger 1000 yeast per colony at the array is 197 millimeters on a side, which goes well with 200 mm integrated circuit wafer technology.
Wikipedia says 1500 varieties of yeast have been given species names. Screening a library of yeast could find yeast that naturally live 10 times longer or more than Saccharomyces cerevisiae, the genome of those yeast could be investigated to find out if there are proteins or other chemicals at those longer lived yeast that function as longevity drugs as well as find genetic sequences at the yeast that make mice live longer.
A liquid fungal growth medium could be poured repeatedly on soil at perhaps 14 different global locations, the soil dug up, then the soil samples mixed with 40 times volume of growth medium, then then the multiple new fungi containing culture medium could be used at a library screening array, likely without isolation of particular species. If it is possible to give fungi cancer with radiation then screening a million or a billion of the chemicals the yeast produce while treating cancer could produce new longevity chemicals (noting senolytics) as well as new anticancer drugs.
New antibiotics and anticancer drugs: The 11 factorial binomat as well as the most fluorescent live longest, which also goes with the dead ones being least fluorescent could also be used to find new antibiotics and anticancer drugs. If rather than yeast, infectious bacteria were grown at a gel medium at a million or billion location array, then binomats or freeze fractured or autolysed screenable libraries could find or make those chemicals and proteins that variously kill bacteria, oncocytes at human tissue culture, or cause them to cease bacterial cytodivision. Another variation on this is that the million or billion item array could be microfluidically exposed to carcinogens to cause 1-10% cancer at human tissue culture cytes at the array, then amongst that 10 to 100 million oncocytes that occur at locatable array locations, compare those locations at a different array, where an anticancer library is screened. That screens 10-100 million possible anticancer and well as cancer preventative chemicals; this is more efficient if the first array is only as large as the number of published carcinogens (10,000?) and then these carcinogens, possibly multiplexed, are placed at all the locations of the million or billion item array which then screens a million or a billion different possible oncotherapeutic drugs and anti cancer drugs and even new cancer preventing drugs.
Screening a library of human tissues: Human tissues, particularly those at well supercentenarians, 80 year old cadavers, kindergarten age children, and teenagers could be autolyzed or freeze fractured, or possibly (although I think there are better things than electrophoresis) electrophoresisized then differentially described and the unique per-age (children, teens, supercentenarians) chemicals quantized with electrophoresis or some other technique, to find out which electrophoresis protein bands were absent in children that were in cadavers, and those protein bands that were in cadavers that were absent from supercentenarians. This would provide a library, the entirity of all the diferential chemical bands from electrophoresis, of possible longevity and youthfulness heightening proteins to screen as a library. There is also the possibility to find out which chemicals and proteins to minimize: chemicals unique to 80 year old cadavers’ tissues and blood, that, if immunized against, could cause greater longevity, as they are what the children and supercentenarians do not have circulating or have being produced.
The idea is to use actual human tissue as a screenable chemical and protein and ion library to find and identify longevity and wellness chemicals using a million or billion item array to see the effect of those endogenous human chemicals. One benefit of screening human tissues and blood, as a library, is that the chemicals and peptides and proteins found have direct applicability and drug utility to human longevity, wellness, and healthspan.
Finding the optimal cadavers to compare the supercentenarians and kindergarteners with: it is possible there is already published research on what otherwise well 20th century persons biochemistry and blood chemistry anomalies were during the year before those 20th century AD persons without cardiovascular disease or cancer died? That noncardiovascular disease, noncancer biochemistry that preceded death by 12 months during the 20th century may be known, or if not, can be figured out. …Perhaps persons that died from pneumonia, flu, kidney illness, accidents and respiratory illness;
“Chronic lower respiratory diseases: 149,205”
At my paper or computer notes, I think are a bunch of repiratory technologies like lung probiotics (possibly including harmlessized beneficial proteus that migrates and produces beneficial peptide or protein drugs), a new one: enzyme-limited dose asthma and other medications, no matter how much you inhale the dose remains the same as it is caused by (turned into functional drug with) enzymes or as a hydrated drug possibly from the thickness of mucous coating, or a new one, senolytics that can be inhaled, perhaps at age 40, 50, 60, 70, 80, 90, 100, 110, 120, 130 and up. liposomal antivirals might be of benefit as well.
Inhaleable gene therapy or probiotics that make growth factors like EGF or VEGF might make a difference, They could blend growth factors until they found something that caused the number of alveoli that spontaneously grow to increase (imagine 50-100%), then administer the therapy to only one lung at a time. Medical improvement of one lung at a time could give people time to heal, and utilize scar-dissolving things, if they exist, along with longevity and beauty peptides, I read there are beauty peptides that increase elastin, and some dissolve scars, “Clinical studies have found that copper peptides remove damaged collagen and elastin from the skin and scar tissue because they activate the skin's system responsible for those functions.” These things could be used to remodel one lung at a time,
Noting that neurons that make the most of the lung capacity a person has could be amplified as to their function with nootropics it is possible inhaled nootropics or oral nootropics could benefit people with COPD.
It is possible that hormesis could benefit people with COPD, possibly causing some tissue regenration, one possibility is that lipopolysaccharides could be the hormetic agent, notably which bacteria that the LPS are made from, and the particular mass fractions of the LPS can be the fresh area of drug research producing patentable material, also benefitting people globally, a LPS inhaler used perhaps 3-11 times, once every few months is likely pretty cheap. There is some mention of LPS at hormetic online, other things that are hormetic like perhaps imitation of light septic shock and things that stress the endoplasmic reticulum. tunicamycin is described as a neurologically beneficial endoplasmic reticulum hormetic chemical https://www.frontiersin.org/articles/10.3389/fncel.2018.00222/full
Dubious yet plausible: Make sports quiz phone apps for each of 5 teams in any state, then at 50 satetes that is 250 clone-like sports quiz apps, globally that is like 3 billion divided by 300 million (US) so 2500 clonal sports quiz apps; the sports quiz apps could have things on how to cease inhaling things that cause COPD, including camp smoke; the sports quiz apps could also have information on how to be a better parent, and even suggest being a better parent could go with children experiencing less smoke of every kind, and possibly gently urge financial generosity towards women and children. At 10,000 people downloading each sports app then that is 2.5k times 10k or 25 million app users, if 1% of them minimize smoke exposure successfully then that is 250,000 people with less risk of COPD. 500,000 if 10 sports teams per 5 million people can be made into quizzes.
Mist makers like nebulizers might be improved with better nozzles, enzyme or hydration activated drugs that cause the same identical beneficial dosages at lung depth or nearer the throat based on enzymatic activity production (and near throat drug absorption reduced to optimal dose); Practice at optimal inhaling of drugs in front of a computer could be beneficial.
Could a virus engineered to produce a beneficial blend of growth factors like EGF and VEGF reach all the alveoli of a one-treated-lung at a time? The concept is that existing alveoli might make more bulbish things.
possibly a hydrophilic protein that rapidly gets degraded so it omits making gooiness could contain active drug, but only release as much drug as there is water surrounding it, suggests finding out what enzymes are at the pulmonary mucosa; perhaps there is a pulmonary ciliary protein that is quite hydrophilic on its own, even puffing up with water but hypoallergenic and immunoneutral. Put that on the outside of imitation liposomes, like liposomes without lipids, with a diffusive drug core; It could be like a ratioized blend of surface flavored jello mixed with gradual flavor diffusion jello to deliver multiple hours of steady plateau-like drug activity.
It is possible that something that increases the number of erythrocytes causing more oxygen absorption with less inspired air could benefit people with COPD; I think I have heard of erythropeotin to make more erythrocytes, and it is possible a new drug could be developed that causes erythrocytes to be recycled every 180 days instead of every 120 days rising the amount of oxygen carrying capacity at the circulatory system 50%.
Noting the fractal nature of the lungs could a combination of postively and negatively charged inhaler nozzle droplets or inhaleable powder reach different areas of the lungs? It seems like no, as drifting mist, or even powder, positively or negatively charged onto water will cause particulate or droplet wetting.
peculiar, but could an effervescent inhlation possibly like Xenon gas pop rocks, cause faster drug delivery from mucous stirring during fizz?
Could muscle building things like creatine benefit the diaphragm, or even SARMS or anabolic steroids to build up musculature at the lungs?
Perhaps a prescriptionless inhaler that only does people good could be of benefit.
I feel perhaps I misunderstand, but this website says that 37,000 people in the US died near 2018 from accidental poisoning, more than vehicle accidents, so globally that is near 720,000 people. Perhaps people’s phones could have an app that tells people what something is, and if they should avoid it. Online it says unintentional misuse of prescription drugs is a part of poisoning numbers. It might be possible to have a deep learning AI and a wall-mounted camera watch people grabbing pills in the bathroom and alert them if something looks dangerous.
Online it says the 9th of 10 leading causes of not being alive during approximately 2018 AD was kidney disease.
Notably though, as compared with diagnostic tissue and blood chemicals it is possible that there are specific chemicals, which if there were less of them, would increase human longevity. Kidney disease might cause a bunch of chemicals to build up in the circulatory system, and some of these could actually be harmful, so treating that chemical symptom could actually cause greater longevity and healthspan. One possibility could be immunizing against those built-up chemicals.
So, wikipedia describes numerous things about kidney unwellness, so is there a wellness kidney function that is at the 99th percentile of wellness, and does it have any healthspan or longevity benefits? Edema, peeing out protein, and those peed out proteins leaving the rest of the body with nonadequate function (like anticlotting something-opposite-thrombin, or other things),
So is there a highly functioning, highly capabable kidney function profile? Is it genetic? Can kidney function be not just restored but brought nearer to optimal at a median person to make it so they are 99th percentile optimized for wellness and longevity kidney function. It is possible growth factors like EGF, VEGF, others could be linked to localizer molecules to generate more, better, or histologically like youth morphology at the kidney.
Causing dialysis to actually increase longevity: people with kidney diseases, wikipedia says, excrete different amounts of protein and other circulating chemicals. It is possible that dialysis membranes that have novel affinities or chemical exclusions could increase longevity and healthspan. One possibility, linked to longevity and sulfur containing amino acids, is to preferentially remove methionine, or inteleukins, although wikipedia says that peeing out lots of protein is a thing that happens with some kidney disease.
Particulalry to increase the wellness of children, liposomal corticosteroids could be orally effective, “minimal change disease that has a remission rate of 95% with corticosteroids”
Also, antibodies are as little as (less than) $399 or $435 gram, so dialysis with antibodies, or antibodies linked to dialysis membranes like to the interleukins, could improve wellness from glomming and removing harmful chemicals.
“nephrotic syndrome. This pronounced loss of proteins is due to an increase in glomerular permeability that allows proteins to pass into the urine instead of being retained in the blood.” reminds me of things that increase or decrease the permeability of the blood brain barrier. Magnesium sulfate causes four times less permeability at the blood brain barrier, perhaps it could also benefit persons with “glomular permeability” and reduce the symptoms and unwellness associated with kidney unwellness, it is likely that has already been thought of, near certainly.
galactose is really bad for people, but small amounts of it are endogenous. It is possible that immunizing against galactose could heighten wellness, healthspan, and sustain cognitive capability.
Cortisol, at wikipedia, notes that cortisone reduces immune system activity while also reducing irritation and puffiness. Noting that there might be many kinds of cortisols based on slight variations of the steroid molecule, it is possible that some people have a wellness and disease-preventing better-homeostasis version of cortisol molecular variants circulating at their body. Sort of like how people can have a different blend of estrogenic molecules and their amounts from each other.
If that is an actual thing, then the genetics of optimal cortisol-like chemicals and chemical variants could benefit humans, that is persons, that is people. Genetics of the morphology of the adrenal glands could effect cortisone response and production, as well as adrenaline linked psychological and behavioral effects. Is there a lively yet cortisol optimized adrenal gland genetics?
Could gene therapy on the adrenal glands optimize wound healing and immune “unrepression opposite of cortisol effects” while still providing the benefits of cortisol? Is there a 99th percentile of adrenal gland wellness which causes people to get sick 1/3 to 1/2 as much from greater immunocompetency and faster healing velocity from less cortisol (note I think wikipediaq says dentists during exams healed 40% more gradually compared with when they were on vacation from higher cortisol)?
As a drug: type and dosage; perhaps deep learning AI could find the right three or four chemical “balance” to simultaneously optimize immune function and cortisol, and cortisol-like chemicals to provide the greatest wellness, “soothed tissues”, while still maintaining immune functions that perhaps could, when optimized, cause 1/2 as much susceptibility to infectious disease progressing to actual perceived symptoms while still having “soothed tissues”. Then again, if a person gets a cold every other year and that’s it, this is needless.
Wikipedia has a chart suggesting the 2019 range of circulating cortisol could vary up to five times, which suggests that some particular discernable amount between 5 and 25 is more optimal.
Time
Lower limit
Upper limit
Unit
09:00 am
140[49]
700[49]
nmol/L
5[50]
25[50]
μg/dL
Midnight
80[49]
350[49]
nmol/l
2.9[50]
13[50]
μg/dL
Wikipedia notes, “In dental students, wounds from punch biopsies took an average of 40% longer to heal when performed three days before an examination [from higher cortisol levels from stress] as opposed to biopsies performed on the same students during summer vacation”
It is possible that rather than just have immunocytes at the circulation they could be part of, linked or tethered to particular tissues, that way as blood flowed past them they would glom things that benefit a human to have glommed, while omitting traveling the whole body and potentially being immunoreactive. local tissue only gene therapy that works like Immunizations against circulating biochemicals could be beneficial.
Gene therapy could possibly cause actual tissue cytes to make actual antibody and aptamer proteins on their exterior cytomembrane, causing noncirculating yet beneficial antibody or aptamer effects. Some possibilities are GI tract cytes, myocytes and hepatocytes making cytomembrane exterior proteins that glom longevity-nonoptimal steroids like testosterone and possibly some variants, depending on further research, of corticosteroids. Also, the amount of actual antibody activity would be related to the generation of new cytes and the tissue and cyte and tissue renewal frequency, so antibodies that reside at the circulatory system-side of the GI tract’s cytes could have multimilligram a day antibody refresh, while antibodies that reside at the cartilige could have a few hundred milligrams produced annually; one benefit of this is that if a medically beneficial thing happens if only 20% of a circulating biochemical is glommed and made nonactive from being removed then having the antibody at the cytomembrane of something that renews every 90 days and is physically sized like a wrist could do the 20%, whereas comparing a bodywide circulating macrophage and lymphocyte response, that might glom 100% of some biochemical or other chemical for decades.
Possible intelligence and cognitive style gene, the BDNF (brain derived neurotrophic factor) gene, “The Val/Val variation of the BDNF gene in men and the Val/Met variation in women are associated with increased salivary cortisol in a stressful situation.”
Longevity technology:
Royal jelly has some proteins and lipids in it and gene therapy could make these at humans, “The average survival times were 88 weeks for the control group vs. 79 weeks for the low-dose group (about 0.6 mg/kg weight), 112 weeks for the intermediate-dose group and 110 weeks for the high-dose group, respectively, showing that RJ extended the average survival time by about 25% compared to the control group.” [27% 88:112]
A probiotic could also be engineered to make the proteins and lipids of royal jelly.
Also, royal jelly lipids could have physiological benefit and be mass producible. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ[royal jelly]
, “10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.” https://www.ncbi.nlm.nih.gov/pubmed/25789174
25 uM royal jelly lipid c elegans dose;
3 times Mouse dose (126 mg/24 hours although it does not say, 3 times (3 times .6 mg/Kg) low dose might be the intermediate dose and have 25-27% mouse longevity increase; also the 126 mg every 24 hours is absent the mouse compensation number which would reduce dose to 10.5 mg/24 hours)
The graphs show 10-30% longer lifespan for different varieties of c. elegans, although one 10-HDA genetic variant lived less long. feeding it to mammals and noting any longevity, healthspan and wellness benefits along with the 25-27% mouse study could make this a beneficial lipid supplement, as its 10-20% longevity effects, at c elegans and 25-27% at mice are greater than omega 3 fatty acids, There is one study showing 25-27% greater lifespan at mice. if it benefits mammals It is even possible that this would benefit people as a germline gene modification.
A different study notes that HDA reduces glucose blood level about 25% via AMPK, at 3mg/Kg or 210 mg per 70 kg human. That is about 21 grams of royal jelly at 1% HDA, or with mouse compensation factor 1.75 grams.
10 samples of “pure royal jelly” were analyzed and “Ten samples claimed to be pure royal jelly, containing 10-HDA between 0.75 and 2.54%”, also lyphilized is 1% HDA.
c elegans lives 10% longer at 10 ug/ml royal jelly, .7 grams per 70 kg person per 24 hours https://www.ncbi.nlm.nih.gov/pubmed/21858156
Also, 10 hydroxy 2 decenoic acid causes c elegans to be about 6 times better at avoiding being dead from warmth, and about 7 times as good as not being dead from poison. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350847/
A protein, and gene that are the mammalian functional-similars to royal jelly at mammals, royal jelly at mammals makes stem cells keep their flexibility (pluripotency): “NHLRC3 [the mammal equivalent of royalactin] appears to be a mammalian pluripotency maintenance factor”,“We next wondered whether a homolog of Royalactin existed in mammals. Sensitive searches of sequence databases using iterative PSI-BLAST23, as well as aiming HHPRED sequence and structural profiles against the human and mouse proteomes24 did not reveal any Royalactin orthologs. However, the latter computational tool revealed that Royalactin is distantly related to an existing structure in the PDB database25, a secreted salivary gland protein (SGP) from the sand fly, L. longipalpis (PDB ID: 3Q6K)26. We then used this structure––a six-bladed β-propeller fold with no additional domains—as an accurate template for MODELLER27, yielding a high confidence model for the Royalactin fold (Fig. 3a). The resulting superposition of Royalactin and SGP sequences was then used to seed new and more precise HHPRED scans of the human proteome, in search of a possible structural and functional analog of the Royalactin/SGP β-propeller fold. Fitting the description of a secreted, single domain chain, with a predicted 6-bladed β-propeller architecture, only one protein, the provisionally named NHL Repeat Containing 3 (NHLRC3), arose as a potential candidate, with striking fold similarity to the Royalactin model (Fig. 3a). Although no known function of NHLRC3 has been identified to date, single-cell RNA-seq analyses of early mouse embryos revealed that it is expressed starting in E4.5 embryos, and that its expression increases steadily thereafter (Supplementary Figure 3a). To elucidate whether it served a functional purpose in stemness maintenance in mESCs similar to that observed with Royalactin, recombinant mouse NHLRC3 was added to mESC culture in the presence of serum/–LIF (serum/–LIF + NHLRC3) as well as 0i (0i + NHLRC3). As seen with Royalactin, NHLRC3 maintained mESCs in an undifferentiated state in both culture conditions for multiple passages (Fig. 3b, c, Supplementary Figure 3b, c), with expected changes in gene expression (Fig. 3d, e). Additionally, injection of 0i + NHLRC3 cultured cells into mouse blastocysts generated chimeric animals with germline transmission, highlighting the robust effects of this protein in vivo (Supplementary Figure 4, Supplementary Table 1). Thus, NHLRC3 appears to be a mammalian pluripotency maintenance factor, whose existence demonstrates a remarkable conservation of macromolecular structure and function. We renamed NHLRC3 as Regina due to its conservation of functions with those of Royalactin and the queenmaker Royal Jelly.”
This is kind of: yuck, but do termites and ants queens have any kind of similar longevizing, sole source of nutrients like queen bees? That could be a source of new longevity chemicals.