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longevity drug: photoactivated brain localized rapamycin

rapamycin makes lab mammals live about 30% longer, but has side effects. concentrating and activating rapamycin at particular areas of the brain could cause greater longevity
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I read that the drug deprenyl concentrates at a part of the brain called the substania nigra, and that it makes 3 species of mammals live 25% longer. I think some researchers think it is from preserving the substania nigra area.

What if you use aptamers (the glomming part of antibodies) to concentrate the deprenyl just at the brain? Might the localization cause greater longevity without alertness (jitteriness) side effects? Another approach is to link the deprenyl molecule to a photoactivatable molecule (like a porphyrin) so that it was only active where lasers illuminate the body?

Either of these strategies could also be used with rapamycin, another longevity drug with crummy side effects. So the technology here is photoactivated, area localized, longevity drugs with fewer side effects.

beanangel, Nov 01 2016

A website of potential anti-ageing compounds http://agefactdb.jenage.de
[MaxwellBuchanan, Nov 02 2016]

phenformin longevity stidies on mammals, at the jenage.de database databse phenformin does about as well as metformin http://lifespandb.s...search?q=Phenformin
[beanangel, Nov 03 2016]


       For those of you who, like me, were confused by the sudden appearance of Deprenyl, it turns out that it's a drug used to treat Parkinson's and which also appears to significantly increase lifespan in rats.   

       Rapamycin is an immune suppressor used to control transplant rejection, and which has also been convincingly shown to increase lifespan in rats.   

       As to using aptamers (which are not, in general, parts of antibody molecules; but which do bind to specific targets) to target either of these drugs to particular regions - I dunno, [beany]. For one thing, just bolting a whopping great aptamer onto a small molecule is likely to mess with its activities. For another, the aptamer would probably stop the drug crossing the blood/brain barrier. And for yet another, I don't think there's any evidence that the longevity actions of these drugs are related particularly to the brain.
MaxwellBuchanan, Nov 01 2016

       I bet the rapamycin mechanism for increasing longevity is the same as the reduced calorie mechanism.
bungston, Nov 01 2016

       Yes, that's the current theory. If you came up with that idea independently, then huge kudos to you, [bung].
MaxwellBuchanan, Nov 01 2016

       //rapamycin mechanism for increasing longevity//   

       Well, yes, the mTOR (mammalian target of rapamycin) pathway is influenced by caloric restriction. There is, of course other things going on.   

       //deprenyl concentrates at a part of the brain called the substania nigra, and it makes 3 species of mammals live 25% longer//   

       bah, now, that's a monoamine oxidase inhibitor, which interestingly is metabolized into methamphetamine... Anyhow, all the life extension stuff is done in animals which don't live very long. That's like making a bus go round a race track faster, it's pretty easy to make dramatic improvements on the baseline, but in the end you will end up needing the strategies that existing racing cars use. Mice, for example, aren't very metabolically adaptable in the same way we are, they get pretty stressed after a few hours without food, we're better at reversibly breaking down and re building tissue over long periods. In addition, we have a whole extra system for redox metabolism, the uric acid system. It's not so well studied (bias toward the systems that exist in model organisms) but it's likely our chief circulating antioxidant.   

       Mice have to be nearly 50 fold better just to get to where we already are.
bs0u0155, Nov 01 2016

       Same thing we do everyday Pinky...   

       [mb] I read at science news there is an antibody drug that gloms onto beta amyloid (unless it is tau) at the brain, so i think apatamers could localize to various brain regions, so getting an antibody drug past the blood brain barrier is a demonstrated technology.   

       I mentioned the substania nigra concentration effects of deprenyl to suggest that longevity effects have been (speculatively, by a scientist) to specific area of the brain.   

       actually though I am fascinated with something you previously wrote, that you have a list of perhaps dozens of longevity chemicals (or possibly factors). If you like describe them at an annotation. even if i did a recombinant effort (titanium resveratrol!) There might be something fresh to think of.
beanangel, Nov 02 2016

       [Bungston]'s comment makes me think that if they could do brain localization of insulin, or a CR mimetic drug perhaps brain aging could be reduced. I once read the brain runs off lactic acid (!) rather than glucose though.
beanangel, Nov 02 2016

       //a list of perhaps dozens of longevity chemicals (or possibly factors)//   

       The list is about 50 items long, and ranges from simple chemicals to things like caloric restriction. However, you can also browse a website devoted to life-extending drugs <link>
MaxwellBuchanan, Nov 02 2016

       // so that it was only active where lasers illuminate the body?   

       We're shooting lasers inside brains now?
Cuit_au_Four, Nov 02 2016

       Yes, but miniature sharks guide them to the correct site.
MaxwellBuchanan, Nov 02 2016

       [mb] thanks for the reference, many of the chemicals were completely new to me, yet there are many published at peer reviewed literature that were missing, so I wrote them a note with some of the missing ones. "Deprenyl (selegiline) 3 mammal species (mice, rats, dogs), about 20-25% greater longevity the peptide epithalon, mammals Reishii fungus, mammals charcoal enterosobent, mammals royal jelly, mammals C60 Buckminster fullerene at olive oil, mammals"
beanangel, Nov 02 2016

       What's the deal with mitochondria or whatever where it loses a chunk every time a cell splits? Isn't that the main time bomb all life forms have at the cellular level?   

       Don't know where I read that. Don't know if it's a theory or fact or even if I'm quoting the concept correctly, but I seem to remember there's more than just getting the chemistry right to get past 150 years.
doctorremulac3, Nov 02 2016

       //What's the deal with mitochondria or whatever where it loses a chunk every time a cell splits?//   

       That's not mitochondria - that's telomeres. Telomeres are short stretches of repetitive DNA at the ends of chromosomes. Every time a chromosome replicates (which happens in cell division), the telomeres get shorter, because the replicating machinery can't copy all the way to the very end of the chromosome. After enough cell divisions, the telomeres are down to zero length, and then further divisions result in loss of important stuff.   

       Mitochondria are little internal structures with their own DNA - they're basically intracellular bacteria, but stripped down. They divide as needed to make more mitochondria. However, their DNA replication/repair machinery isn't perfect, so they tend to accumulate mutations and become dysfunctional with age.
MaxwellBuchanan, Nov 03 2016

       [drremulac] the mouse genetically engineered to live twice as long as controls was engineered to make more telomerase as well as a cancer preventing thing called p53. A human, Elizabeth Parish, has sought out telomere lengthening with gene therapy to improve her longevity. So if you have some extra money, there is a human protocol.   

       Also if you are willing to order deprenyl and phenformin [link] (or metformin) online you might live much longer for less than $365/year.
beanangel, Nov 03 2016


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