• Royal Jelly, Longevity, and Novel Longevity Technologies

    From Julia Amara@21:1/5 to All on Sun Jul 23 07:36:20 2023
    Longevity technology

    Royal jelly is published as making mice live 25 (27%) longer, and queen bees live about 36 months, 12 to 24 times longer than other bees; noting that insect chemicals can cause mammals to live longer, it is possible other long lived insects could have
    chemicals that cause greater longevity. The mice that were longevized with royal jelly were fed it orally, bringing up the possibility of change to the proteins in it; some insects, queen termites, live 50 years, with some possibility of 100 years,
    feeding ground up insects to mice, both orally and as enteric capsule or coated material could find out if the ground up material of long lived insects cause greater longevity; another approach is to extract circulatory fluid (hemolymph) from these
    insects and find out if it makes yeast or c elegans or fish live longer, notably, fish as vertebrates could be notably suggestive of mammalian activity; another insect to screen for longevity chemicals are cicada nymphs (17 years), beetles of the genus
    Eleodes (up to 17 years)

    longevity technology: I perceive I read playing back EEGs causes the brain to be better at learning and can reactivate emotions; it is possible that rather than EEG, electrical recordings from the surfaces of children and 16 year olds could be played
    back at the body surface to find out if it has any longevizing, wellness, or healthspan effects; this could be tested on nude mice, and might go well with the body and tissue thickness of mice as proof of concept; at humans something like a wireless
    recharging near body surface implant (kind of like a pacemaker) could provide the youthful EEG-like stimulus, notably it is possible that wave and frequency variants like nodal, antinodal or possibly depth-reaching electrical solitons https://phys.org/
    news/2006-05-solitons-electronics.html (dissipative solitons, 100 times farther travel than regular solitons) could be used; notably, some current levels and alternate voltages for the EEG-like frequencies could be used to possibly reach tissues at
    greater depth, as could wrist-to-wrist or leg to wrist, or even head to calf electrode placement

    EEG playback technology: playing back EEGs to cause beneficial cognitive effects using different voltages or currents to reach deeper into tissue, notably though some currents and voltages might verge into tDCS (although AC-like) which is a different
    thing; the previously described gelatin capsule sized piezoelectric frond hair adhering and head skin seeking technology could also do some tDCS as well as EEG recording, playback and software based synthesis; children’s EEGs could also be played back
    at adults to find out if there were child-mind effects as well as, just possibly, longevising, wellness, or healthspan effects (seems unlikely, but is possible), notably children have more delta waves, and these occur during sleep, although less so at
    older people, these child EEG frequencies could be played back while adults sleep; this could be tested on rats, or some larger animal like cows, sheep, or horses

    Longevity technology: Some biologically occuring tings do rapamycin like things https://www.ncbi.nlm.nih.gov/pubmed/29165314 It is possible that mutating these plants, then screening their chemicals on yeast and things like c elegans with 96 well plate
    technology could create much larger rapamycin like longevity chemicals at plants, these could then be genetically engineered into delicious as well as ubiquitous plant foods to create longevity producing fruits, grains, and food products like pasta,
    pizza, potato products, breading, there is also the possibility that moving these gnes and gene products from plants to eggs and milk could be beneficial

    a molecular variant or rapamycin, rapamycin preassociated (attached) to a protein makes it 2000 times more active, “To probe the affinities involved in the formation of the FKBP.rapamycin.FRB complex, we used fluorescence polarization, surface plasmon
    resonance, and NMR spectroscopy. Analysis of the data shows that rapamycin binds to FRB with moderate affinity (K(d) = 26 +/- 0.8 microM). The FKBP12.rapamycin complex, however, binds to FRB 2000-fold more tightly (K(d) = 12 +/- 0.8 nM) than rapamycin
    alone. No interaction between FKBP and FRB was detected in the absence of rapamycin. These studies suggest that rapamycin's ability to bind to FRB, and by extension to mTOR, in the absence of FKBP is of little consequence under physiological conditions.
    It is possible some molecular version of rapamycin (a rapalog) could cause mTOR activity without FKBP protein, FKBP has immunoeffects so that molecule could have less immunoeffects than rapamycin

    Rapamycin that is more water soluble, “clinical development of its formulations was hampered due to its poor solubility and undesirable distribution in vivo. Chemical modification of rapamycin presents an opportunity for overcoming the obstacles and
    improving its therapeutic index. The objective of this study is to develop a drug-polymer conjugate to increase the solubility and cellular uptake of rapamycin.
    METHODS:
    We developed the rapamycin-polymer conjugate using a novel, linear, poly(ethylene glycol) (PEG) based multiblock copolymer. Cytotoxicity and cellular uptake of the rapamycin-polymer conjugate were evaluated in various cancer cells.
    RESULTS:
    The rapamycin-polymer conjugate provides enhanced solubility in water compared with free rapamycin and shows profound activity against a panel of human cancer cell lines. The rapamycin-polymer conjugate also presents high drug loading capacity (wt% ~ 26%)
    when GlyGlyGly is used as a linker. Cellular uptake of the conjugate was confirmed by confocal microscopic examination of PC-3 cells that were cultured in the presence of FITC-labled polymer (FITC-polymer).
    CONCLUSION:
    This study suggests that the rapamycin-polymer conjugate is a novel anti-cancer agent that may provide an attractive strategy for treatment of a wide variety of tumors.” hydrophilic rapamycin combined with regular rapamycin could reach a wider variety
    of tissue types, combined they could cause greater than the 60% longevity increase published at mice
    Optically activated rapamycin, “We developed an optically activated rapamycin dimer” perhaps a topical benefit
    focusing rapamycin effect on just one tissue (kidney), “Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most
    prominent in close vicinity to the implanted microspheres.”
    longevity technology: Liver function genes, like SNPs, could be a source of new longevity drugs, gene therapy or also germline gene modification, “To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the
    transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed
    significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a
    change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial
    function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.” They could do this analysis at a variety of tissues,
    including the gut, which I perceive I read secretes and might process a lot of physiochemicals
    liposomes http://www.ijper.org/sites/default/files/IJPER_45_4_13.pdf
    liposomes might or might not benefit rapamycin, a way to tell is if rapamycin has nootropic characteristics, possibly at a higher sample dose, and then see if a liposomal version causes more nootropic effect, notably though liposomes might cause longer
    plasma half life and could possibly have different peak plasma concentrations so that might effect a nootropic effect
    about 76% of some actual rapamycin liposomes get turned into liposomes, with the rest at the remaining fluid, that suggests drinking the extra fluid, or eating the trehalose it might be dried out on could provide another simultaneous, possibly different
    tissue specific activity of rapamycin
    depending on if phosphatidylcholine or phosphatidyl serine turns into, or is highly similar to phosphatidic acid liposomes made of these might be nonpreferred, suggesting a different liposomal production method “the efficacy of rapamycin is dependent
    on the level of phosphatidic acid (PA), which is required for the assembly of both mTORC1 and mTORC2 complexes. Rapamycin interacts with mTOR in a manner that is competitive with PA. Therefore, elevated levels of PA, which is common in cancer cells,
    increases the level of rapamycin needed to suppress both mTORC1 and mTORC2.” liposome preservatives and how long liposomes last with refrigeration, “The use of cryoprotectants such as dextrose, sucrose, and trehalose may increase stability from hydrolysis. Also, samples may experience oxidation upon storage. The addition of
    small amounts of antioxidants during processing may stabilize the suspension and limit oxidation of the product. SUV should be stored above their transition temperature for no longer than ~24 hours. LUV may be store for a longer period of time if stored
    at 4-8°C when not in use. Hydrolysis of the lipid begins to occur immediately resulting in monoacyl derivatives (Lyso lipids) which act as detergents and disrupt the membrane, thus permeabilizing the membrane. After ~5-7 days at 4-8°C the internal
    contents will begin to leak indicating hydrolytic degradation of the lipid. If membrane structure is not a critical parameter in your experiments, vesicles may be stored for 1-2 months with minimal (<10%) hydrolytic degradation.”
    distilled water is likely a way to make liposomes be longer lasting, “or by binding metal ions that initially induced aggregation. However, the presence of aggregation can accelerate the process of coalescence of liposomes”
    ions at a solution could cause liposomes to last less long, that suggests when making liposomes drug and lecithin, or purified phosphatidylcholine, amounts at something like ultrasonication to make the most liposomes per volume, it is also possible
    filtering or centrifuging (?) liposomes could divide it from a fluid which might have uncombined, particularly oxidizable drug or phosphatidyl choline molecules
    If there are longer versions of phosphatidylcholine they might make more durable liposomes, “Permeability and stability of liposomes are influenced by the rigidity/stiffness of the lipid bilayer.”
    liposome size depends on how they are made, ultrasonication produced liposomes make “small unilamellar vesicles (SUV), 25 to 100 nm in size that consists of a single lipid bilayer.” shaking a liposome making solution with your arms makes “Large
    unilamellar vesicles (LUV), 100 to 400 nm in size that consists of a single lipid bilayer. Multilamellar vesicles (MLV), 200 nm to several microns that consist of two or more concentric bilayers.” it is possible a combination of all three types reaches
    a wider variety of tissues and likely has greater physiological activity and physiological availability than rapamycin at an enteric capsule
    “liposomes prepared by using combinations of some lipids follows the order of physical stability form the correlation of the mean volume diameter, zeta potential and pH , egg lecithin (PC)/cholesterol (CH)/stearylamine (SA) < PC/CH/phosphatidylserine (
    PS) < bovine brain ceramides (CM)/CH/palmitic acid (PA)/CS < PC/CH/cholesteryl sulphate (CS) at 4°C, as well as at 25°C, 2122after a 6-month storage period” also, “Vesicles composed of saturated phospholipids were found more stable compared to
    phosphatidyl-choline(PC) liposomes”
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    All technologies, ideas, and inventions of Treon Sebastian Verdery are public domain at JUly 8,2023AD and previously, as well as after that date

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