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longevity thrill drug (nicotine linked to metformin)

metformin causes some mammals to live longer, they are testing this now on humans. Linking metformin to nicotine creates a chemical that could replace the worlds second most popular recreation drug with a new one that makes people live longer
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metformin causes some mammals to live longer, they are testing this now on humans. Linking metformin to nicotine creates a chemical that could replace the worlds second most popular recreation drug with a new one that makes people live longer.

so, about the molecule, there are a variety of places the two molecules could attach to each other. To find the ones that have active longevity effects as well as neurological effects a library of molecules (as it is called) with about 1000 variations of how the two molecules connect is screened at 96 well plates.

Each each well at the plate has a c. elegans worm at it. Thus video screening only about 11 plates can process all 1000 molecule variations. The c elegans will live longer at the most effective longevity versions of the molecule and the wiggle rate might be highest at the most active nicotine effect versions of the molecule.

Those versions of the molecule with heightened longevity and lots of wiggling could be tested on mice.

Now, screening a library is the way to go, yet it is also possible to seee if obvious works. One of the methyls on metformin could connect directly to the methyl on nicotine. Also nicotine phenformin might be much better as the dose of phenformin is a few milligrams. phenformin is iffies to attach to nicotine, yet it is possible that the nicotine could be attached at the ethyl area in the middle of phenformin.

Mice and or rats (do not remember) lve about 20-25% longer on phenformin.

beanangel, Apr 17 2017

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging http://www.cell.com...092-8674(17)30246-5
[xaviergisz, Apr 17 2017]

longevity studies of c elegans using 96 well plates https://www.ncbi.nl...gov/pubmed/21445049
[beanangel, Apr 19 2017]

[link]






       I missed the part where you explained why linking together two active and beneficial molecules into a probably inactive conjugate was a good idea.
MaxwellBuchanan, Apr 17 2017
  

       My 72 year old diabetic friend consistently gets top marks on her medical check ups; her doctor says her levels are all better than folks 25 years younger. In fact, she's the poster person for 'how to control diabetes with diet and exercise and sheer bloody-mindedness'.   

       She usually takes a very low dose of metformin and always chews nicotine gum. Coincidence?!
Sgt Teacup, Apr 17 2017
  

       While we're on the topic of longevity, what's your opinion of the linked article [MB]?
xaviergisz, Apr 17 2017
  

       Well, I don't have access to the journal (and hence the article), so I can only see the abstract. But Cell is a good journal, so it's probably not a whacko article.   

       One thing I note: they claim (in the "highlights") that their peptide induces apoptosis (death) of senescent cells; and that death of sensescent cells has fitness benefits. But they don't say that their peptide has fitness benefits, which is odd: it's a statement they would have made if they'd been able to.   

       Edit: they do make that statement in the abstract; not sure why they chose that wording for the "highlights".   

       If anyone has access to the journal and can send me a PDF, I'd be interested in reading the article.
MaxwellBuchanan, Apr 18 2017
  

       Having a nicotine molecule tacked onto a metformin molecule doesn't seem to be particularly worthwhile as such. There are other nicotinic substances though. What this makes me think of is the mental health issues which people self-medicate using nicotine, which could get them somewhere. However, nicotine and to some extent other nicotinic substances do nastinesses to you which would, I think, wipe out any benefit from the metformin.
nineteenthly, Apr 18 2017
  

       //nicotine and to some extent other nicotinic substances do nastinesses to you// Not really. They're addictive, but not harmful as far as has been shown, I believe.
MaxwellBuchanan, Apr 18 2017
  

       The antiandrogen effect of metformin does not get too much press. I suspect many of its nonglucose-related beneficial effects have to do with that. Androgens are not good for the long term. Males are the shock troops of the species.
bungston, Apr 18 2017
  

       Pretty sure the metformin assertions in this idea are true from what I've seen.   

       Problem is, don't know how it's tolerated in "overdose" amounts. If you make it addictive...   

       hey! Screw the nicotine, put it in ice cream!
doctorremulac3, Apr 18 2017
  

       //Pretty sure the metformin assertions in this idea are true from what I've seen. // Yes, metformin and its relatives, as well as a host of other chemicals, show life-extension (and health-extension) results in animals, often up to and including mice/rats. The big problem is to validate them in humans; not only are the studies difficult (because of the timescale over which they have to run), but you need to be especially sure that there are no adverse effects, if you foresee millions of people all taking these compounds for decades.   

       [bsu] was kind enough to send me a PDF of the paper cited by [xavier]. It does look quite good, and it's not written by either whackos or by people from a nation known to not be above a little complete fabrication. I think they could have done more work on naturally aged mice, but these things take time. (Most of their mousework is on a fast-ageing strain of mice, and studies like that are always a bit dodgy.)   

       All in all, we should expect it to be quite easy to extend healthy human lifespan by a large factor - certainly easier than curing cancer, for instance. With cancer, we're trying to add defences to a system that has been evolved and refined over hundreds of millions of years; with ageing, we're just trying to do something that evolution hasn't really even considered - so there's scope for very fast improvements.
MaxwellBuchanan, Apr 18 2017
  

       // Not really. They're addictive, but not harmful as far as has been shown, I believe.//   

       I hope you are not being influenced by my recent postings which although a true personal account are not part of any statistically significant survey.   

       Today I was surfing for any symbiotic relationship with nicotine and survival. Of course I got nowhere besides some studies linking neurochemical 'deficits' to a genetic cause for additions.   

       Did it ever occur to these people that when you talk about a breeding population that the environment of the breeding organisms is also important ? Simple fictitious example "Take the human out of the 2000 year old herb garden and its less likely to survive". Or a concrete example from history - "Learn to make beer or boil water or die".   

       That might be a bit simplistic, but hundreds of years ago knowledge was part of the longevity of an organism. So now I'm wondering whether nicotine, the new wanted poster enemy of the prohibition lobby actually also has some symbiotic value with humans on a biological level rather than just adding that Bohemian Rhapsody touch to everyday life.   

       Based on the current level of medical understanding I'll probably never know the results of an accurate study, in the same way as not being around for the results of surgically attaching kittens to people.
bigsleep, Apr 19 2017
  

       There are certain substances which there's too much going on around to come to any sensible conclusions about their benefits or deficits. Cannabis is a definite example there because there's a lot of pressure from either side to praise or condemn it. I suspect nicotine is similar. But the thing is, in that situation, in the absence of information you can trust, it's probably best to avoid acting on any evidence.
nineteenthly, Apr 19 2017
  

       I think (and no, I haven't researched it in depth) that a great deal of research has been done on nicotine, especially by the anti-smoking lobby (which is just about everybody). Yet despite this, there is probably about as much evidence for harm from nicotine in "normal" doses as there is for caffeine; and there are plenty of studies indicating the neuroprotective effects of nicotine. For instance, proof that it delays the onset of Parkinsons disease has been around for decades; and I believe that there are plenty of studies showing benefits in slowing dementia and in improving the memory and general cognitive function of the non-demential elderly.   

       Basically, nicotine is not necessary for a healthy life, but does seem to be widely beneficial; it's just that those benefits are usually more than offset by the delivery system.   

       This should not come as a surprise. There are all kinds of drugs that are generally beneficial (aspirin, on balance; supplementary vitamin D in most cases; statins probably; metformin and a host of other anti-ageing drugs potentially). The fact that one of them is a plant alkaloid is not very surprising, and the fact that it's enjoyable is a happy coincidence. We should make the most of it.
MaxwellBuchanan, Apr 19 2017
  

       //not being around for the results of surgically attaching kittens to people//   

       However, there is a benefit of surgically attaching young mice to old mice, at least for the old mouse. Blood from young mice reverses many of the effects of ageing in the older mouse. They have gone on to show that serum from young humans can have a similar effect on old mice. There is a reasonable chance that serum from young humans would also benefit old humans.   

       This does raise the prospect of vampirism reappearing, but it's unlikely that the active compound(s) would survive the digestive tract. It's much likelier that they'll track down the specific compounds involved, and make them available synthetically.
MaxwellBuchanan, Apr 19 2017
  

       //This does raise the prospect of vampirism reappearing,//   

       There goes the pro-smoking lobby.
bigsleep, Apr 19 2017
  

       //There must be a whole lot of other plants that can be smoken// I believe that cannibis is quite popular amongst young folk, and poppy extracts have always been a winner. And others too numerous to remember.
MaxwellBuchanan, Apr 19 2017
  

       I improved the idea to be more plausible about finding the right molecule.   

       new text   

       so, about the molecule, there are a variety of places the two molecules could attach to each other. To find the ones that have active longevity effects as well as neurological effects a library of molecules (as it is called) with about 1000 variations of how the two molecules connect is screened at 96 well plates [link].   

       Each each well at the plate has a c. elegans worm at it. Thus video screening only about 11 plates can process all 1000 molecule variations. The c elegans will live longer at the most effective longevity versions of the molecule and the wiggle rate might be highest at the most active nicotine effect versions of the molecule.   

       Those versions of the molecule with heightened longevity and lots of wiggling could be tested on mice.
beanangel, Apr 19 2017
  

       Does x-formins cross the placental membrane ?
wjt, Apr 20 2017
  

       search engine says "At present, metformin is classified as Class B in pregnancy, with no evidence of animal or fetal toxicity or teratogenicity. Reproduction studies in rats and rabbits show no teratogenicity with dosages up to 600 mg/kg per day, approximately twice the recommended human dosage"   

       pregnancy plausible!
beanangel, Apr 20 2017
  

       And the social implications on future fetuses? without a warp drive. Death does give someone else a go.
wjt, Apr 22 2017
  

       //Basically, nicotine is not necessary for a healthy life, but does seem to be widely beneficial//   

       Specifically what I have been wondering is if nicotine can be beneficial, have some humans adapted to it genetically ? Much in the way the western world genetically adapted to the consumption of alcohol. Alcohol isn't necessary to live, but there is no doubt various gene pools have adapted to have a vastly increased tolerance to alcohol.   

       Ok, weird examples - my blood pressure is still +20 to +40 over what it was when I was smoking (12 weeks ago now). In my early teens I used to think my tongue was too big for my mouth, and now after quitting, skin, gums and tongue swollen. I have to be careful chewing as my tongue is again too big for my mouth. This implies to me genetic coding for a smoking preference, either that or a bad aubergine habit as they also contain significant quantities of nicotine.
bigsleep, Apr 22 2017
  

       People do differ a lot in how quickly they metabolize nicotine - I can't be arsed to go and look up the relevant gene, but it's known. People with a fast nicotine metabolism are more likely to smoke more than people with a slow nicotine metabolism (to maintain adequate levels of nicotine), though I don't offhand know how the gene relates to the tendency to smoke or not.   

       It's likely that the relevant proteins are also responsible for breaking down other plant alkaloids, many of which are harmful.
MaxwellBuchanan, Apr 23 2017
  

       //the relevant proteins are also responsible for breaking down other plant alkaloids//   

       Now we're getting somewhere. Plant alkaloids are a defence mechanism which get expressed more the younger a plant is. Unripe tomatoes or sprouting potatoes - all pretty dangerous.   

       So basically I come from a long line of idiots who didn't know how to store vegetables and as a consequence I have hypertension if I don't smoke.
bigsleep, Apr 24 2017
  

       Well, only part of that statement has been verified.
MaxwellBuchanan, Apr 24 2017
  
      
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