229 replies to this topic

[John Schloendorn]

if it can be done in stealth

No LysoSENS worker will process any samples that have no verifiable origin of the highest ethical standard. We have obtained graveyard soil in the past, with permission and cooperation of the graveyard operators. Based on these data, there is no striking reason to believe that graveyards enrich for the type of organisms we want, but the question is not conclusively answered at this time.

[Karomesis]

No LysoSENS worker will process any samples that have no verifiable origin of the highest ethical standard.

John, is it possible to approach the FBI or another forensic anthropology lab and ask for samples from the "body farm"?

http://en.wikipedia.org/wiki/Body_Farm

thus circumventing any moral quandaries.

[John Schloendorn]

Possible, but I have in the past considered other activities a better use of my time. Again: There is no reason to think that pillaging rotting corpses will do us any good, and some theoretical reasons (discussed amply above) to expect otherwise.

[soren]

Righto.
In that case, I shall ask the trustees of the cemetery behind my house, Abney Cemetery, - an old haunt of Edgar Allen Poe's no less.
It is a very old one, with burials dating from the early 19 century, and a very high density of burrials, due to the massive shortage of space back in Victorian London.
I have done conservation work for them, they owe me this much at least!
May I just ask, did you take deep soil samples from the cemeteries you spoke of (By which I mean three or four feet down or more)?
(Please rest assured, I would not use a shovel! I would use a sample collecting push stick) with the Trustees permission only.

[John Schloendorn]

All: We're having a bit of a carboxymethyllysine culturing project going on right now, and could use an infusion of fresh samples anytime from now till November. Those of you who are near any biodiverse or exotic habitats, please send us something over.

Raiding graveyards may make for a good story to tell, but is still discouraged for the above reasons.

By regular mail:

John Schloendorn
The Biodesign Institute
PO Box 875701
Tempe, AZ 85287-5701
USA

(The above address cannot receive FedEx / UPS shipments)

By FedEx / UPS:

John Schloendorn
The Biodesign Institute
1001 South McAllister Ave
Tempe, AZ 85287-5701
USA

(The above address cannot receive regular mail -- sorry about the trouble)

[maestro949]

I've seen mentions of engineered mouse strains for things like Alzheimer's. How difficult would it be to develop a mouse strain for LysoSENs and other aging-related amyloid targets? Do mice even die of or accumulate aggregates or does cancer usually kill them first?

More generally, is there a potential "set" of mice that could be engineered that serves as a basis for the SENS 7 that could serve as better models for the MMP?

[John Schloendorn]

I've seen mentions of engineered mouse strains for things like Alzheimer's.

"Wild-type" lab mice do not usually develop age-related storage diseases. To make suitable models it takes indeed gene targeting.

How difficult would it be to develop a mouse strain for LysoSENs and other aging-related amyloid targets?

It is probably not necessary for LysoSENS workers to develop our own models, because others have already done so and they are usually in the public domain. For Alzheimer's, it was quite difficult, e.g. it took three separate genetic interventions to make them recapitulate the human pathology reasonably close.

More generally, is there a potential "set" of mice that could be engineered that serves as a basis for the SENS 7 that could serve as better models for the MMP?

No. The longevity prize requires a long-lived strain that is not messed with as the control group. The rejuvenation prize requires that any intervention be begun at half the mean age. Gene-targeting can only be done in the germ-line, and therefore any such model is disqualified. Using gene-targeted mice in general for the Mprize would not make sense, because you could extend their life simply by putting the missing genes back in, or compensate for their absence in other superficial ways not related to human aging, and it is not clear just what would count as such, because we understand so little of metabolism. Therefore, life-extension of long-lived wild-type mice should send the more powerful message for now.

Do you have a suggestion of a particular genotype that should be permitted?

[Karomesis]

Those of you who are near any biodiverse or exotic habitats, please send us something over.

John, forgive my ignorance, but by "biodiverse' do you mean that rainforest soil would be a great sample?

it would seem it's both biodiverse as well as exotic.

[maestro949]

"Wild-type" lab mice do not usually develop age-related storage diseases. To make suitable models it takes indeed gene targeting.

It is probably not necessary for LysoSENS workers to develop our own models, because others have already done so and they are usually in the public domain. For Alzheimer's, it was quite difficult, e.g. it took three separate genetic interventions to make them recapitulate the human pathology reasonably close.

No. The longevity prize requires a long-lived strain that is not messed with as the control group. The rejuvenation prize requires that any intervention be begun at half the mean age. Gene-targeting can only be done in the germ-line, and therefore any such model is disqualified. Using gene-targeted mice in general for the Mprize would not make sense, because you could extend their life simply by putting the missing genes back in, or compensate for their absence in other superficial ways not related to human aging, and it is not clear just what would count as such, because we understand so little of metabolism. Therefore, life-extension of long-lived wild-type mice should send the more powerful message for now.

Do you have a suggestion of a particular genotype that should be permitted?

The only ones that came to mind were variants that had different amyloid buildups as they seem like they'd be reasonable to develop if strains can be developed for Alzheimer's. If there are already mice for LysoSENS then you answered my first question.

As far as more suitable strains, I was thinking that perhaps that there might be variants for the other SENS damage types. Variants that reduce mouse lifespans such that the damage kills them before cancer. This would provide strains that would allow us to test therapies for any one of the SENS 7 independently.

Edit: Fixed horribly written sentence

Edited by maestro949, 25 October 2007 - 11:40 AM.

[John Schloendorn]

biodiverse' do you mean that rainforest soil would be a great sample?

Yes, rainforests are a classical "high biodiversity" habitat.

As far as more suitable strains, I was thinking that perhaps that there might be variants for the other SENS damage types.

Some such mice exist, e.g. with increased rates of mitochondrial mutations, or diabetic mice for increased crosslinking. Actually I think there's a mouse with accelerated accumulation of at least one example of damage for pretty much each of the 7 categories.

[kclo4x]

So i don't know if this thread is still useful, or if they still want dirt since i have read very little about this subject, but anyways!
I have a tank full of soil, that has "thousands" of pill bugs in it, a lot have died, more have had offspring. i have added a lot of things to it for food, since pill bugs eat everything pretty much.
it has had pretty much everything in it:eggs, meat, various vegetables, some multivitamins, protein powder, sugar, other types of dead bugs, bird seed, etc.
Since there is such a diversity of material this soil, i bet there would be a lot of different types of bacteria that normally wouldn't be found outside.
Would this be a good source for any type of useful bacteria?
I could try to do some other things with it such as make one jar of dirt acidic, the other basic and then incubate them in my little junky homemade incubator?

If this soil seems like it could be useful, maybe i could add other things as well to increase the possible useful bacteria?

Have any comments on this?

[thestuffjunky]

you still want samples? i am new and will love to help in any project i can. so, i live in kent ohio. regional composition is marsh/bog. there are a few spots i can go to that are ideal of mentions you mentioned. let me know and you can donate the postage...

thank you derek

[Mind]

Results!

DETAILS IN A NEW FRONT PAGE ARTICLE

Published in Rejuvenation Research: http://www.lieberton...9/rej.2009.0917

Abstract:

A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age—atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechnism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.

[John Schloendorn]

Great, thanks for everything, ImmInst members! Feel free to hit me up if you need a reprint of the paper.
My dissertation containing all the details will be published some time in spring. It will be online and free open access.

Both SENS Foundation and my former professor and collaborators are now working to develop these discoveries into therapies. The professors at Arizona Biodesign and Columbia University won a grant from a mainstream foundation to continue this work. It is enough money to keep them in the game for the next three years, towards pre-clinical testing in cell and maybe animal models. So this work has been able to graduate from the immortalist family -- It seems fair to say LysoSENS has become mainstream.

SENS Foundation is rumored to be well situated in the coming year too, and may still collaborate with the professors if necessary. So, looks like everything is very much on track to continue. Thanks to everyone for helping to make this happen.

[Ghostrider]

Great, thanks for everything, ImmInst members! Feel free to hit me up if you need a reprint of the paper.
My dissertation containing all the details will be published some time in spring. It will be online and free open access.

Both SENS Foundation and my former professor and collaborators are now working to develop these discoveries into therapies. The professors at Arizona Biodesign and Columbia University won a grant from a mainstream foundation to continue this work. It is enough money to keep them in the game for the next three years, towards pre-clinical testing in cell and maybe animal models. So this work has been able to graduate from the immortalist family -- It seems fair to say LysoSENS has become mainstream.

SENS Foundation is rumored to be well situated in the coming year too, and may still collaborate with the professors if necessary. So, looks like everything is very much on track to continue. Thanks to everyone for helping to make this happen.

John, I am very glad to hear about your success. I have been following LysoSENS over the past 4 years and it's very satisfying to hear about my donations to SENS bringing some great results to the development, pre-clinical, and hopefully clinical stage. I feel confident that the successes from LysoSENS, once they are finally translated into therapies, will generate some serious attention / show accomplishment -> raise credibility and consequently accelerate the rate of funding for SENS and its resulting therapies. So congrats! Do you plan to continue working on LysoSENS or shift your focus to another branch of SENS?

[JLL]

Fantastic. I remember Aubrey briefly mentioned this in his speech, but I didn't realize we were so close to seeing results.

[Mind]

As mentioned previously, the Immortality Institute and its members played a key role in the successful launch of LysoSENS. It is this type of collaboration that typifies the more open source can-do research attitude of recent years and hopefully will lead to more valuable discoveries in the future. Many thanks to all those who sent in soil samples and the members who conducted the research.

It took a while to get to this point and now the tough part begins - testing the enzymes for human use - which will probably take a few more years, but it is great to see progress in engineering an end to aging. This is just the beginning! I am hopeful that the Institute will be able to continue to participate in AND fund similar collaborative research in the future. In fact, I would personally give preference for grants to researchers who have a plan to involve the community in the research (such as with LysoSENS).

Thanks to everyone who sent in the soil samples! Thanks to all the Imminst members who were in the lab testing the samples and isolating the enzymes!

P.S. I highlighted 4 Imminst members who were authors of the paper (Justin, Kent, Mark, & John). There might be a couple more who are registered here at Imminst that I am not familiar with - at least not their Imminst name. If anyone knows of more people in the list of authors that could also be recognized as part of our community let me know.

[tlm884]

Is this still an active project?

[John Schloendorn]

My dissertation detailing the research methods and results of this work went online http://gradworks.umi...92/3392127.html

[GabrielPaparella]

John, thank you for choosing this specialty!

So you've discovered that human lysosomes can break 7-ketocholesterol down into 7KC esters palmiatate and linoleate but can't break down the esters, unlike bacteria which can. And you've identified a cholesterol oxidase from Brevibacterium sterolicum that converts 7KC to a less toxic 3,7 diketone compound. You lay out the possibility of testing the cholesterol oxidase enzyme from Pseudomonas florescens, which can degrade the 7KC esters, in a foam cell culture model.

Wow! This looks like it could really work! I hope that such a model will be done soon, and we can move into animal studies that address atherosclerosis as a Lysosomal Storage Disorder delivering the enzymes you identified. 28% of people die of heart disease. That is not a small number.