Banishing lonliness with a 1000 year functional depot injection or possibly as a combined effect with another drug could cause 26% less mortality, ““Imagine a condition that makes a person irritable, depressed and self-centred, and is associated with a 26 per cent increase in the risk of premature mortality,” Cacioppo and her late husband, John Cacioppo, wrote in The Lancet last year. Around a third of people in industrialized countries report feeling lonely, one in 12 severely so” https://nationalpost.com/health/all-the-lonely-people Notably the steriodal hormone pregnenolone has been researched as an anti-loneliness drug, and as a sex steroid like molecule could have ethynylization as well as halogenation as effective dose multipliers; the first page of a search engine suggests 10 times greater effect per dose, if ethynylization is 8 times greater dose efficacy then 80 times fewer micrograms per dose could be possible; at .625 mg as a daily estrogen dose, and 300-800 nanogram/24 hours at ethynylized estrogens or possibly progesterones (progestins), the fluorinated version could be active at 30-80 nanograms/24 hours, or a .333 gram depot injection providing 365,000 to one million gradually diffused 1microgram to 100 nanogram doses at a one office visit dose treatment for loneliness, a 1000 to 10,000 year duration of loneliness reduction if pregnenolone has a ethynyl and fluoro dose amplified form. If a lymphatic system applied depot form of ethynylated halogenated progesterone is possible that approximately quadruples physiological availability from omitting first pass metabolism; if a blood brain barrier passing moeity is a possible modification as well a two to ten times greater availability at the CNS, a possible location of feelings of loneliness could be possible, so 80 nanograms /4 /2 is 10 nanograms per 24 hour dose, permitting an approximately 40 milligram 1000 year duration depot injection dose. Notably, if it is possible to make an oral depot version of a drug, possibly from antibodies linked to palmitates, with the antibodies specific to lymphatic epithelia, then at 10% efficiency compared with an injected depot a 400 mg depot producing oral dose with 1000 year depot functionality of a ethynyl fluoropregnenlolone could be possible; gene therapy or also germline gene therapy to produce more pregnenolone, or shift to personality genetics that is absent feelings of lonliness; also noting that the big five personality test trait areas are about 50% heritable, and that a new personality test where, like the minnesota multiphasic personality inventory the questions were correlated, winnowed, and enhanced to be predictive, it is possible a 97-99% genetically predictable paper question or also software psychology test with completely fresh new traits that could also be called themes could be constructed. If some percentage of these traits or themes that are 97-99% genetically predictable are the kinds of things people would change to improve their well being, efficacy, ability, and prosociality, reduce or prevent loneliness, while maintaining or expanding creativity and initiative then those are rapidly eugenics addressable traits and themes that could also be gene therapy opportunities.

Addressing loneliness with depot drugs or causing greater plasma levels from less pregnenolone metabolism, whichever is more physiologically beneficial could reduce mortality 26%. It is unknown if numerous species of mammals along with humans experience loneliness, gene drive could banish loneliness at perhaps all mammals; the effect on frequency of mating and the number of progeny is unknown, but imaginably increases among all mammals that experience an absence of loneliness.

Moieties that cause higher physiological availability and physiological activity at a particular mg (or mcg or ng) dose; I read that halogenated drugs are less metabolized at the liver with things like CYP enzymes, that gives longer plasma duration, as well as possibly omits first pass metabolism, causing, imaginably, 90% or higher amounts of the drug to remain fucntional at the circulatory system; It could be that there is a kind of drug visiting and detaching from receptors many times, as well as what I previously thought that halogenated drugs glom on to receptors and have long residence intervals from their high electronegativity glomming and staying on a receptor; also it is possible that halogenated drugs, as well as other drugs, which get some of their durability from plasma from glomming to albumins, globulins, or other plasma proteins could have versions that glom to plasma proteins twice as avidly, or perhaps are absent any plasma protein glomming; a fluorodrug without plams protein glomming might go almost completely unmetabolized at the liver, yet have a tissue available dose 7-9 times higher from an oral or other dosing; alternately, double duration plasma protein glomming

screen a library: radiolabelled or fluorophore labelled halogenated drugs, a few thousand, million, billion, or at a 300mm integrated circuit wafer with 1 trillion wells

Rapamycin, with like a trifluoro (methyl group like with three fluorines) that has 16 day or longer plasma half life, different plasma protein glomming could be an even more effective enhanced human longevity drug, from persisting at the circulatory system longer; noting the mice that lived 60% longer from 126 ppm rapamycin had frequent meals but, I perceive I may have read, 9 minute rapamycin plasma half life, and I might have read human plasma half life of rapamycin might be .9 hours while wikipedia says 57-63 hours; higher plasma protein glomming of a rapamycin; wikipedia says rapamycin is 92% protein glommed, there is some possible greater sustained rapamycin longevity effect there that could be produced and be beneficial; wikipedia says, “ Since albumin is alkalotic, acidic and neutral drugs will primarily bind to albumin.”; Although a trained professional would know much more, the longest plasma half life of a drug I am aware of is norfluoxetine, 16 days, 384 hours; perhaps the chemistry of such drugs (trifluoride like a methyl) could be used to produce even more beneficial, possibly even more longevizing variations of rapamycin, noting the mice were likely eating food perhaps every few minutes at the 126 ppm enteric coated rapamycin dose; At the rapamycin molecule I read that a /\/\/\/\ with numerous \=/=\=/=\=/ is thought to be the mTOR active part of rapamycin, and it has a methyl on it that if replaced with a trifluoro methyl like moeity could cause the ten times greater plasma half life. It is different than other things I have read, but wikipedia says ascorbic acid has a circulatory system half life of 83 days, with an eleimination constant of 4 months, that suggests something as simple as screening a variety of locations of an ascorbic acid moeity could make a 3 month dose of a longevity producing rapamycin varaint; also I perceive I read that rapamycin’s oral absorption has to do with rapamycin’s nonsensitivity to pH, a rapamycin ascorbic acid version could have higher effective drug absorption at a particular mg or ppm at food dose;

Longevity drug: 126 ppm rapamycin is published as making mice live 60% longer, it is my perception that I read this has to do with reducing mTOR activity, notably though mice with mTOR -/- genes, which I pereceive as meaning they have zero mTOR receptors live 20% longer; It seems possible that at mammals with mTOR receptors the mammals might also be making previously unstudied slightly hormesis-like chemicals that cause other changes at the body to compensate or emeliorate for having mTOR receptors, and possibly reducing the activity of things (networks) connected to mTOR receptor activation; those slightly hormetic like ameliorators persist at the mammals when rapamycin causes the 60% greater mouse lifespan yet at the -/- mtor mice are minimally there ( genes that produce the ameliorating chemicals) as they do not need to be. Finding those physiochemicals, likely proteins, receptor proteins or material at the cytoplasm then adminstering them to mammals as separate longevity chemicals as drugs could have the 40% longevity increase that could be linked to 60% increased longevity mice (minus) 20% at mice with no mTOR receptors; At humans, production of these chemicals, proteins, or peptides could be endogenous with germline gene modification or also gene therapy; The possibly attainable 40% greater longevity from other mTOR receptor presence ameliators might even have different tissue or cyte localizations, potentially concentrating longevising effects, or finding areas to bring up to the body tissue longevity increasing median, which would cause greater youthfulness of phenotype as well as greater longevity; looking at all the mRNA that rapamycin causes the production of, and comparing it to the mRNA that the mTOR -/- mice when adminstered rapamycin make could find the ameliator 40% greater longevity genes and chemicals, just administering rapamycin to the mTOR -/- mice could find the 40% longevity mTOR ameliorating chemicals, genes, and proteins or peptides from mass characterizations at all the proteins and peptides produced at the mammals.

Moving a math distribution of longevizing drug effects with bulk-effect different longevity drugs, and comparing that to a conctenated tissue and cyte approach; is there published research on the distribution of phenotypic and genotypic youthification of form (variously somatic form or things like telomeres or mRNA expression profiles) at different cytes and tissues, It is possible an equation, computer model, or predictive AI would be much better, although one way to think of this is like a histogram; if the histogram has a normal distribution then 32% of tissues and cytes are high longevity responders, 68% are at the first standard deviation; broad-group differences in distribution shape, and addressing which cytes and tissues are at what standard deviation could be a programmatic way to find composite longevity drug combinations that cause a chemical that causes the phenotypic or also genotypic central standard deviation of one drug to be at the 2nd standard deviation of longevization with another drug; this bulk mathematical effect complements the other idea of finding things like: one thing functions at adipose tissue, one thing works at neurons, another thing works at the cardiovascular system, another works on preventing cancer then assembling a multitissue multicyte addressing multidrug blend; both have value, it is just that addressing entire distributions to move up an entire standard deviation of longevity increase could be accomplished with particularly larger affordability, and simplicity.