44 replies to this topic

[treonsverdery]

This recent paper http://www.ncbi.nlm....les/PMC3156754/ has a graph where at week 45 three quarters of control mice had died whereas 4/5 given LKM512 probiotic bacteria were still alive. Viewing the graph this protocol more than doubles mammal lifespan with a probiotic. There is a yogurt with LKM512 prominently displayed on its packaging available now http://jpabc.net/new...view-17399.html . I urge people to start making this immediately at the United States
 lkm512.gif   16.11KB   13 downloads
 imagesearchlkm512.jpg   15.8KB   14 downloads

It would be wonderful if there was a version with a fluorescent protein so the fecal fluorescence of the lab mammals could be compared with the fecal fluorescence of human probiotic supplement users to create a visually verifiable equifunctional dose

The article suggests that polyamines at the GI tract cause the longevity effect

Edited by treonsverdery, 24 February 2012 - 01:07 AM.

[niner]

Something is up with these mice; the controls are only living on the order of 300 days. Those mice are seriously messed up. I'm all in favor of probiotics, but in all likelihood this result will not translate to other healthy mammals.

[brunposta]

Hi niner,

I took a look at the paper, and it seems like the graph above is referred to the duration of the experiment:
"The solution was administered 3 times a week, starting when the mice were aged 10 months.".
Anyway, they also state that the control group had an unusual short life compared to other longevity experiments on this strain of mice: "At less than 36 weeks of treatment, the median survival of the control group was less than 19 months, which was considerably short in comparison to those reported in other longevity studies conducted in mice.". In other experiments they use to live between 850 and 900 days (~ 30 months).
Sso yes, there's might to be something fishy here, starting with the fact that the study was carried in (and probably financed by) the same company who produce the LMK512 yogurt.

[treonsverdery]

its got me thinking if transfecting (gene therapy) the GI tract to make polyamines would be a one time drug that strongly increases human lifespan. The Gi tract has rapid tissue recreation though so I don't know if it would persist long as compared with a probiotic.

This link has a color version of the graph which contains more data than the plos paper with the polyamine spermine having an effect http://www.kyoto-u.a...11/110817_1.htm
microsofttranslator version http://www.microsoft...11/110817_1.htm  01.jpg   27.46KB   4 downloads

Polyamines http://en.wikipedia.org/wiki/Polyamine are chemically amusing looking NH2/\/\NH2 or NH2/\/NH\/\NH2 just a hydrocarbon with amines on it.

A variety of transgenic mice that make more polyamines have been produced http://herkules.oulu...148.html#AEN343
It appears that where there is a surplus of which polyamine makes a difference. Longevity studies on these polyamine superproducing transgenic mice are the thing to do particularly a version that superproduces spermine.

also you can view a video on youtube that links to the LKM512 paper also shows a mouse eating yogurt
http://www.youtube.com/watch?v=2O5ThmgKFBM

Edited by treonsverdery, 24 February 2012 - 03:17 AM.

[treonsverdery]

Spermidine possibly part of LMK512 effectiveness has been published as increasing the longevity of human tissue culture cytes http://www.mendeley....otes-longevity/


 200px-Spermidine-2D-skeletal.png   2.5KB   15 downloads
Also thinking about a version of spermidine that is more effective I thought of the bizarre populist named AmineEagle, or possibly aminedove, yet like naming something after a mean dove sounds iffy.

 longevity chemical.png   8.05KB   18 downloads

spermidine looks kind of like a dove, or an eagle nh2/\/\nh/\/\nh so if you make bigger wings with unsaturated links at the far edges the combiningness of the nh2 group varies, which should vary its physiological effects. nh2=c/\/nh\/\=nh2 of course you can locate the nonsaturated links anywhere to create spermidine variants to see which most promotes mammal longevity. nh2/\/=nh\/\nh2
(?) might also be possible

partial saturation c=c like that is linked to color at molecules, the mild color shifts from grouping c=c links near each other suggest mild changes to the activity of the nh2 amino groups. also creating c=c at the far edges creates greater molecular flexibility right at the phytsiological receptor

as spermidine promotes longevity at human tissue culture finding the saturation variant that most promotes tissue culture longevity could be a way to preimprove the human applicability of the mouse study.

another approach to to turning this doubles mammal longevity effect into a supplement is to create a fungal or mushroom extract. At week 40 spermidine alone 3 mg per kg, 3D per W, actually doubled mouse lifespan, spermidine causes the "spermatic" odor of some mushrooms, creating a superconcentrated extract could mimic the effects of LMK512 or the green spermidine data. the MSDS on spermidine says its wildly dangerous as a fluid, if a person casually thinks about it as like triamine octane (its actually more like a heptane or decane)it sounds explosive n smelly so 200 mg of spermadine directly at a pill is kind of amazing.

[Googoltarian]

Where did you get this yellow picture? Those structures are very unlikely to exist in a living organism, especially this enamine part - it hurts to look at it

First article I found on this said that cis isomers are more active, not trans as you drew them all.

[Mind]

Any chump who takes reasonable care of mice can get them to live to a median of 900 days, with 10% living to 1100 days. This result is mildly interesting and could lead to some new insight, but it is no breakthrough for lifespan extension. (others would say much worse about a study like this)

[MrHappy]

There is something suspect about the control group lifespan. This study needs to be repeated independently before I'd get excited. :(

Edited by MrHappy, 25 February 2012 - 08:40 AM.

[treonsverdery]

Well a few thoughts on longevity yogurt

you can make as much as you like just with moving a starter culture thus this supplement only requires getting once. It would be nice to visiblize it though, I wonder if bacteria are light polarizable genetically, that way you could verify the concentration at feces without going fluorescent. I wonder if yogurt people sometimes add more sugar to their probiotic yogurt to grow an even higher number of beneficial bacteria. If this LKM512 had GFP then you could see if adding sugar upped the color thus the activity level.

When I wrote about possible variants of spermidine I did not describe halogenated spermidine. Halogenation frequently makes pharmaceutical molecules 10 to 100 or even 700 times stronger possible (compare cortisol to fluorocort) changing the dose to just 2 or 3 milligrams. Also the length of the alkane could be varied, or the molecule attached to another molecule that makes it particularly good at passing ion channels or concentrating at particular tissues. These are public domain ideas. An actual drug researcher could still get a patent based on precisely which atom location is halogenated or the specific length of the variant alkane.

Further, that superexpression of spermidine at transgenic mice actually goes back to 1991-1993 makes me think a particular longevity grant could occur
To benefit humanity a fund could be created where any lab experiment where the treated mammals lived 20 pct longer than the untreated group automatically received funding to continue the experiment until the natural death of all the organisms as well as provide supplemental funds to keep an image like video record of the physiological variation amongst the groups. That genetically modified superproducers of spermidine were first created at 1991-93 yet the longevity effect only noticed during 2011 suggests value to gathering full data.

Noting the LKM512 fed mice lived more than twice as long It is possible a continuous video record would show different age at hair whitening as well as rate of hair whitening, measuring the similarity of these curves between spermidine n LKM512 would provide greater numeric support for similar mechanism of chemical action between spermidine n LKM512

Also camera placement provides different data that differing researchers may value. a highly placed camera could record longer retention of original hair color as well as rapidity or gradualness of motion yet a mouse level camera could better detect reduction of cancer as well as mammary cancer thus providing different groups with very valuable data

As the FDA has approved latisse It is possible the demonstrating sperimidine or a variant that changes the start or rate of the whitening of hair could be approved particularly as it also reduces cancer as well as longevizes lab mammals. The observations of actual rate of change of human hair remaining its natural color longer could be fairly rapid.

I have this idea that if the LKM512 researchers reviewed their data with a different mathematical technique they could find a p ratio as to the amount of longevity from spermidine at the 512LKM512 yogurt group. Possibly they would measure the mg/kg of spermidine present at the yogurt, then attribute the multiplied amplitude of the longevity of the actual spermidine only curve to just spermidine. This could be used to provide two new P values from the data the P number from nonspermidine yogurt ingeredients as well as a kind of metaanalysis P number for all spermidine content from both groups. If using a well described math technique that P value on two treatments, each with spermidine may have a more accurate P number than the spermidine alone group.

Kind of like if we gave two groups of mice Honeydew melon with deprenyl, as well as another group of mice just deprenyl.
The deprenyl alone group lived 27 pct longer. They honeydew melon with depreneyl group lived 33 pct longer. Each mouse received .05 mg/kg at the deprenyl only group, they honeydew melon with deprenyl group received .07 mg/kg deprenyl along with the honeydew melon.

calculate the P value of the effect of .05 .06 as well as .07 on the population. I have seen a similar mathematical effect used on the effect of DHA at breastmilk possibly at the actual text of this study http://www.ncbi.nlm....pubmed/15499945

Edited by treonsverdery, 28 February 2012 - 02:06 AM.

[smithx]

I'm going to pick some up when I'm in Japan next month and culture it to make more yogurt but I'm a bit concerned that over time some other bacteria may take over the culture.

Is anyone here familiar with this type of bacteria? Can one dry or freeze the yogurt and use it years later as a starter culture?

I know other bacterial survive freezing, and drying but I'm not sure about these.

Edited by smithx, 28 February 2012 - 08:29 AM.

[sdxl]

I'm going to pick some up when I'm in Japan next month and culture it to make more yogurt but I'm a bit concerned that over time some other bacteria may take over the culture.

Is anyone here familiar with this type of bacteria? Can one dry or freeze the yogurt and use it years later as a starter culture?

I know other bacterial survive freezing, and drying but I'm not sure about these.

Since the yogurt contains 3 bacteria, the ratios of these bacteria may shift when growing them yourself. The bacteria can be infected by bacteriophages, the culture might get contaminated with unwanted micro-organisms especially in a home setting and extensive re-culturing.

Freezing might work. Drying most definitely not.

[treonsverdery]

you can get a GFP transformation kit online http://www.carolina....tby=bestMatches just $21 to $67 I think there are instructions at an MIT amateur bioengineering site on how to bring GFP to other organisms than e coli or lactobacillus. With GFP longevity yogurt you could verify a constant dose

I suppose the daring wealthy could do HPLC to verify that the spermidine content was similar between batches as well

Edited by treonsverdery, 28 February 2012 - 08:37 PM.

[treonsverdery]

[Methos000]

I'm all for probiotics, and while I do take them...I'm not really expecting much if any extra lifespan as a result.

[treonsverdery]

They could make a variation of LKM512 that cures or reduces diaper rash that way people could start their being on earth with the longevity bacteria

I read an article that refered to peer reviewed research that says you can actually trace who people are descended from based on their bacterial DNA as it has been transmitted from parent to child for a while. Thus giving babies LKM512 could actually persist as a longevity benefit throughout their lives.

I think something like pH or poo composition could affect diaper rash thus creating a variation on LKM512 that created much greater longevity as well as cured diaper rash is possible. Absence of diaper rash is a less fussy happier baby which benefits parents directly regardless of how the feel about doubling human longevity.
Note LKM512 is published as more than doubling mouse longevity

[xEva]

Google says it's Bifidobacterium animalis subsp. lactis. The same bacterium (diff. strain) as "Bifidus regularis" in Dannon yogurt.

Everything new is well forgotten old. Over 100 years ago Nobel laureate (1908 for his work on phagocytes) Élie Metchnikoff claimed that supplementation with lactic acid bacteria should prolong life by mediating chronic inflammation caused by metabolites of Gram-negative anaerobes that tend to dominate in adult gut with age. He believed the toxins they release into the circulation were the driving force in chronic diseases of aging. At some point he even advocated colectomy (removal of colon) but later on settled for supplementation with specially collected strains of Lactobacillus bifidus (== Bifidobacterium species after the 1960s).

He personally followed his own advice (starting in his midlife or later) and lived about 20 years longer than was average for his close relatives, who were not known for their longevity -- something Metchnikoff was well aware of and, far from expecting to break the human longevity records, hoped to preserve his health and working capacity as much as his genetic heritage permitted.

[treonsverdery]

From what i have read online different bifidobacterium (Bifidobacterium animalis subsp. lactis) versions do different things.
http://www.ncbi.nlm....pubmed/22384059 notes that of 88 bifidobacterium , 4 had particular ability to hydrolize sennosides (make natural laxatives from prechemicals). Similarly at a different article a new version of bifidobacterium that has ultra high GI tract survival is described http://www.ncbi.nlm....pubmed/20474053 . So there is a difference between the varieties. Wikipedia says Dannon uses DN 173 010 which is different sounding that LKM512.

New to this area is that fructooligosaccharides apparently double the amount of spermidine at the GI tract. spermidine is the chemical that had similar beneficial longevity effects as LKM512. Thus supplementing with fructooligosaccharides could also have a longevity benefit http://www.ncbi.nlm....2079/figure/F1/

From what I read The dannon yogurt appears to kind of like an anti-gas variety, LKM512 appears to be a chemocreator of GI tract motility that also makes a bunch of polyamines variety.

Edited by treonsverdery, 15 March 2012 - 05:47 PM.

[smithx]

I found a place selling LKM512 online as powder which is supposed to be added to milk to make your own yogurt.

http://item.rakuten....km512-teiki-fst

It's in Japanese, but there are services which will ship Rakuten orders anywhere in the world.

Then add some of this to the milk to get more benefit as noted above:

http://www.iherb.com...-113-g/696?at=0

Edited by smithx, 16 March 2012 - 06:24 AM.

[treonsverdery]

One of the effects noted at the paper as well as google images is that LKM512 causes mice to have skinnier less swollen or nflamed GI tract, so that brings up the longevity theories that have to do with is reduced nflammation is longevity beneficial. There is also a genetics of longevity study opportunity, do people or mice that reach much greater than usual ages have genetically skinny (narrow), less swollen GI tracts, if they do, then that effect may contribute to the genetics of longevity thus describing a new longevity gene people can have.

regarding the LKM512 source I would be sure to test to see if it actually makes the chemical spermidine, one HPLC on dried bacteria could verify the stuff is as it says it is.

[treonsverdery]

Finding New longevity genes with spermidine receptors

Noting that spermidine as a polyamine apparently creates 4/5 of the effect of the yogurt, does spermidine function directly as a chemical or does it activate cytoreceptors. If it activates cytoreceptors then the genetics of those receptors are longevity genes. like if a mammal has twice as many spm receptors maybe it lives lots longer. My perception is that the yogurt scientists think the reduction of swelling as well as nflammation contribute to mouse longevity. Another paper http://www.ncbi.nlm....pubmed/19593412 says

Spermine (note highly similar polyamine to spermidine) effectively inhibited HMGB1-induced release of the above surrogate markers in peritoneal macrophages. Thus, spermine confers protection against lethal sepsis partly by attenuating sepsis- and HMGB1-induced inflammatory responses.

Apparently spermine, which as a molecule is like a twice as lengthy spermidine, affects HMGB-1 receptors, so variation at the genetics of that receptor could be longevity genes to verify with mice or studies of very long lived humans.

[MarcD]

Commercially available food more than doubles mouse lifespan ... the controls die in very short time

[treonsverdery]

"shrug at marcd" the thing is to to create more studies on this valuable longevity effect.

actually if the spermidine longevity well being is well supported it goes with a nifty idea I have to make all the commonest materials verifiably beneficial. Right now when people produce something it is permitted unless shown to be harmful. That is fine, the thing is that many of the bulk chemicals that people use could be sourced around the idea of active benefit, so something like CeSpermidine Ce\/\/\/NH/\/\/NH2 with its similarity to octane, nonane, decane, could be a gasoline additive that actually causes mamma;ls to live longer with greater neurological resilience as it casually opposite of polluted the natural environment. The element Ce as well as some other lanthanides has been shown to improve mouse or rat cognition as well as stress resistance. compare something like ferrocene, a known additive to Ce ferrocene, or polyamine "waxes" that have spermidine like beneficial effects while improving gasoline.

as a molecule so similar to an alkane that is highly beneficial it is possible aminated hyrocarbons like spermidine could be things like paint solvents or consumer plastics additives. These would be additives that actually caused benefit on ingestion or exposure. Creating an ethos of build new consumer chemicalsd that cause active benefit as compared with merely being thought harmless could improve peoples well being

thus far gas additives (polyamines), plastic additives(polyamines, polymer dha) , wheat(aedg, ndga peptides), rice(aedg, ndga peptides), lubricants(dmso, dha), preservatives(many published as giving mammal longevity) all have an identifiable chemosimilar that actively improves longevity, well being or neurological capability. as bizarre as it sounds im trying to figure out a plywood adhesive as well as a concrete material that also increase human well being. It is possible thay plywood or concrete that have beneficial microorganism spores gradually weather to create LKM512 like effects at their surroundings. so basically musty damp buildings would happen to make people well rather than ill.


also here is a spemidine patent
Application number: 10/566,411
Publication number: US 2006/0252838 A1
Filing date: Jul 30, 2004
http://www.google.co...rmidine&f=false spermidine is patented as regenerating as well as youthifying dermis
The nifty thing is that the patent from 2004 is on a pill that makes people more beautiful Thus there is a published oral spermidine supplement with researched efficacy on human tissue


 spermidine regeneratwes dermis gives youthful appearance.PNG   131.01KB   8 downloads

Edited by treonsverdery, 26 March 2012 - 06:49 PM.

[treonsverdery]

It is possible spermidine may have different effects at different chronological ages.

[treonsverdery]

Notably spermidine is a NH2ized alkane. It is possible putting NH2 groups on the surface of longevity doubling buckminsterfullerene creates another longevity compund with two active functionalities that double lifespan

[Benedictus]

Ignore the yoghurt part, it's all about the probiotics in it.
Lactobacillus reuteri DSM 17938 is much stronger than LKM512 in regards to lifespan, but either way, go to a Mediterranean country, eat some of the dirt in the mountains, chew some fresh Thyme, take some fresh cheeses from (local, organic) cows and goats, swim in mountain streams there and you'll be carrying numerous beneficial bacteria in no time.

[sdxl]

Ignore the yoghurt part, it's all about the probiotics in it.
Lactobacillus reuteri DSM 17938 is much stronger than LKM512 in regards to lifespan, but either way, go to a Mediterranean country, eat some of the dirt in the mountains, chew some fresh Thyme, take some fresh cheeses from (local, organic) cows and goats, swim in mountain streams there and you'll be carrying numerous beneficial bacteria in no time.

Where is your proof that BioGaia strain does anything with lifespan?

[Benedictus]

Where is your proof that BioGaia strain does anything with lifespan?

BioGaia strain? BioGaia is a brand, does not have 'strains'.
Either way, you're new to the internet, I take it? I mean, you've never heard of google, wikipedia, PubMed etc. ?

I'll help: http://en.wikipedia....sults_in_humans

Edited by Benedictus, 04 May 2012 - 09:44 PM.

[sdxl]

BioGaia strain? BioGaia is a brand, does not have 'strains'.
Either way, you're new to the internet, I take it? I mean, you've never heard of google, wikipedia, PubMed etc. ?

I'll help: http://en.wikipedia....sults_in_humans

BioGaia is a company which owns the rights to DSM 17938, a strain commercially known as Lactobacillus reuteri Protectis. Claiming DSM 17938 is superior for lifespan to LKM512 is a bold statement, since you can't even post an abstract proving DSM 17938 increases it.

[ta5]

Another yogurt mouse study posted recently to the CR list.

http://www.scientifi...ales-eat-yogurt

Mice That Eat Yogurt Have Larger Testicles
Probiotics may endow rodents with a "mouse swagger"
By Elie Dolgin, May 4, 2012

[TRUGAN]

Still no where to buy  LKM-512 ?