229 replies to this topic

[eternaltraveler]

Also, keep in mind that we need to find a nutrient permitting simultaneous degradation of 7kc anyway, to make it accumulate metabolites later.

Of course, but a constitutive mutant would do that with almost any nutrient.

As far as making one, it was just a thought I had. It might be wise to keep an eye out for one that we create along the way with all the other mutants we're making.

[John Schloendorn]

Ah, I see that first point was moot.

Second point, ok but if we keep doing what we do, then we'd almost certainly not recognize such a mutant when we had one. Also I'm not making new mutants anytime soon, but rather getting the accumulation and transformation to work with what we've got. I'll keep it in mind though.

We should skype some time and coordinate better.

[John Schloendorn]

Ah, I get you. Changing the substrate specificity of existing, previously discovered enzymes is something that is discussed in the bioremediation review, as a way of making the microbial enzymes therapeutically relevant (after they have been discovered) and also fine-tuning them to the conditions they are to encounter in the body. There were more concrete plans to change the substrate specificity of existing cholesterol oxidase to exclusively accept oxysterols, using techniques similar to the one you cite, but I have nothing to do with this branch of the project (yet?), and I am not sure if that is taking off.

What I was talking about above was the de-novo evolution of enzymes from random, or only slightly biases sequence libraries. Unlike the 10 to the 5 sequences achievable with current microbe surface display assays, mRNA display has access to some 10 to the 14, enough to evolve active enzymes from random sequences, which look like nothing seen in biology. I believe this is the way to go if one is looking for things like a highly specific beta-amyloid peptidase (which is not directly covered by "microbial infallibility").

[MichaelAnissimov]

So, this effort is called lyso-SENS, even though it addresses many other types of cellular junk aside from lysosomal junk? This was confusing to me at first. In his blog post on the topic, Reason seems to miss this distinction.

[John Schloendorn]

I guess "Lyso" is just chemistry language for ripping stuff apart in all sorts of ways, as in hydrolysis, pyrolysis, lysophosphatide, and whatnot. You are correct that the lysosome is just one of the places where we would like to do this.

[maestro949]

Congratulations John!

The Biodesign Institute at Arizona State University has awarded biochemist John Schloendorn a $30,000 scholarship that will enable him to pursue anti-aging research as a Ph.D. student in the School of Life Sciences. ...

Link...

[penrose]

I just found this project and sent in a few samples. The post office said it could take 8 days to arrive.

A few samples were from my back yard and a nearby part of Philly's large Fairmount Park. Another was some water from the dirty filter of my fish tank(hope that's not too common). Of course, I included the chocolate fee required to have the samples accepted.

Also, earlier you mentioned having tried cat feces. Would it be useful for me to send a sample of droppings from the riding horses or many geese in the park? And what else useful can you think of from a large city as old as Philadelphia?

[John Schloendorn]

Ah I had missed this earlier, thanks guys!

Penrose, they arrived, and we took DNA, many thanks! Sure, your other ideas sound great. I remember one of the early cholesterol eaters has been isolated from horse excrement. 7-ketocholesterol and the other stuff has not been attempted.

[Neurosail]

Want some white sand? I got some from Fort Walton Beach, near Pensacola, Florida from my last vaction. I could place it in whirl-pak bags. How much do you need? Would 4 or 5 24 ounce whirl-pak bags be enough? There is some plant life mixed in the sand.

Edited by Neurosail, 07 December 2006 - 07:09 PM.

[John Schloendorn]

Sounds good, but if you have one without plant parts that would be even better. If not, I can remove them, that's ok. It is important to get rid of all the plant parts, because even a little root will contain much more DNA than all the microbes in the soil. So most of the DNA would come from a single species, which would reduce the diversity of the DNA library.

[Neurosail]

Ok. I will mail it Monday. I'm off this weekend so I will have time to remove as much plant parts as I can.

Good Hunting!

[icyT]

This is definately pretty cool, the news about the guy who found a sample in an old graveyard was really cool. Going for human remains is definately more likely to contain compounds for breaking us down, although looking in animal is good too because ideally we want to extend the lives of animals as well as humans, both as pets and mine canaries It's too bad this practise, much like stem cell treatment, would probably have a lot of objectors and seem creepy.

I may be wrong, but is one of the reasons humans have high atherosclerosis our long lifespan that gives it longer to accumulate? Could it also be our consumption of cholesterols/fats in high quantity on a consistent basis with not enough antioxidants able to keep them stable, compared to animals who eat meat raw so it has more vitamins to keep it stable? Still probably better off avoiding all that bacteria but it could explain why we die of arterial disease at an older age compared to animals dying of infections and sicknesses at earlier ages.

Since our lifespan has grown so much recently, really old corpses probably won't have the level of arterial plaque our elderly do nowadays. Differences in diet may have made it less common too, are there stats on it? The corpses that exist with arterial plaque adequate to host such bacteria may not have been around long enough to develope such bacteria yet?

One idea I had sorta... why don't we breed mammals (mice probably) who will have high levels of this plaque, trying to accumulate the highest level of possible (you'd need to prolong death) and then dump their remains into a very warm place (as opposed to the cold earth as normal) to be the ideal environment for the remains to be processed quickly so we can get samples.

Or possibly... can live people contrbute? Sometimes people have surgery to remove clots, why not give the option of donating these clots to science so we can monitor what would break them down. Nothing better for getting a focused sample than mainly clots.

[John Schloendorn]

one of the reasons humans have high atherosclerosis our long lifespan that gives it longer to accumulate?

Yes, that's a way of looking at it. Humans, pets and lab animals seem to get aging in general, because they eliminated most other causes of death, and extended their lives for longer than evolution designed any maintenance process to run. Which processes fail first could be determined as a side-effect of the sum of traits that are beneficial while young (antagonistic pleiotropy). In humans that happens to be mostly the maintenance of the arteries (-> heart attacks), while in mice it happens to be mostly control of cell proliferation (-> cancer). Not sure if this is directly due to the absolute difference in life-span, as controlling cell proliferation may be just as difficult over long times as maintaining arteries, or even more difficult. Yet humans are relatively better at it than mice.

The corpses that exist with arterial plaque adequate to host such bacteria may not have been around long enough to develope such bacteria yet?

I don't have enough data to answer this question yet.

One idea I had sorta... why don't we breed mammals (mice probably) who will have high levels of this plaque, trying to accumulate the highest level of possible (you'd need to prolong death) and then dump their remains into a very warm place

One would rather chemically synthesize the pure compound, because the major portion of tissue samples is very nutricious and would divert the selective pressure. This strategy has not made it onto my personal agenda just yet, but others have experimented with it with quite some success.

Sometimes people have surgery to remove clots, why not give the option of donating these clots to science so we can monitor what would break them down.

This is mainly interesting if one wants to look at many compounds at once, rather than one pure chemical. Something along these lines is on the agenda, but not a priority now.

[eternaltraveler]

QUOTE
The corpses that exist with arterial plaque adequate to host such bacteria may not have been around long enough to develope such bacteria yet?

I don't have enough data to answer this question yet.

I have anecdotal reports from anatomists and coroners that atherosclerotic plaque is one of the first things to decompose. Now whether that is just all the other stuff in it besides oxysterols breaking down, I don't know. I wouldn't be surprised if it was the sterols as there seems to be plenty of diversity on what can eat the stuff.

[eternaltraveler]

One idea I had sorta... why don't we breed mammals (mice probably) who will have high levels of this plaque, trying to accumulate the highest level of possible (you'd need to prolong death) and then dump their remains into a very warm place (as opposed to the cold earth as normal) to be the ideal environment for the remains to be processed quickly so we can get samples.

I had a forensic examiner who was going to help me get samples from the coronary arteries of fairly decomposed human remains. That fell through as they moved to a different location. I do have some connections that *might* be able to make such a thing happen in the future if we think it's worthwhile.

[austinwiltshire]

Has anyone had a chance to petition one of the 'body farms' around the country? They are run by forensics people to study how bodies decompose, they might be interested in the results of donating a few grams of soil.

[Live Forever]

Has anyone had a chance to petition one of the 'body farms' around the country?  They are run by forensics people to study how bodies decompose, they might be interested in the results of donating a few grams of soil.

Hmm, not sure. (maybe John will see this and would know) I saw a recent video lecture by Aubrey de Grey where he mentioned about how they were using microbes found in soil from near decaying bodies, but I don't know what soil source he was referring to. He could have meant graveyards. (actually, he may have said and I just may be forgetting what he said)

[Aegist]

Has anyone had a chance to petition one of the 'body farms' around the country?  They are run by forensics people to study how bodies decompose, they might be interested in the results of donating a few grams of soil.

That is a very very good idea. I was wondering about getting soil samples from a cemetary and it seemed like taking the topsoil wouldn't be good enough (since the bodies are 6 feet deeper), and that digging down to get closer to the body would be 1. Not allowed, 2. very weird.

So if you could just contact one of those body farms and see if you could get soil samples from some of the older bodies, or even better, from sites where there used to be bodies many years ago.....

[Liquidus]

So if you could just contact one of those body farms and see if you could get soil samples from some of the older bodies, or even better, from sites where there used to be bodies many years ago.....

I think in the name of science, they probably would let you do this provided the right circumstances. If there's legitimacy in a scientific study, they would probably understand the significance. I know it might be not true in a super conservative state, but who knows, it's worth a try at least.

[John Schloendorn]

Again, we are probably not interested in the microbes present while a body is of forensic interest, because during this time there are the fast-growing degraders of common chemicals present. We on the other hand are looking for slower degraders of comparatively rare, and bizarre chemicals. So active decay would for all that we know enrich against the microbes we want.

I wonder if there could be an increased chance of finding degraders of the rare, weird chemicals we are interested in, in the general area of sites of regular deposition. We did obtain some samples from such areas, but do not have enough data to answer the question at this time.

[Live Forever]

I know it is probably something that you have no way of knowing at this point, but, John; Do you think that a place where lots of animals die (where either there might be a lot of animals that naturally die, or there might be a lot of animals that are hunted and killed by predators) would have similar microbes to those around a human graveyard?

I know it is pure speculation and you have no data to back it up and all that, but could it be that there would be similar microbes that know how to break down the same enzymes? Feel free to totally disregard my question. ), but I just thought of it after passing a kind of "animal graveyard" type of a place when hiking a couple weeks ago.

[eternaltraveler]

I know it is probably something that you have no way of knowing at this point, but, John; Do you think that a place where lots of animals die (where either there might be a lot of animals that naturally die, or there might be a lot of animals that are hunted and killed by predators) would have similar microbes to those around a human graveyard?

I know it is pure speculation and you have no data to back it up and all that, but could it be that there would be similar microbes that know how to break down the same enzymes? Feel free to totally disregard my question. ), but I just thought of it after passing a kind of "animal graveyard" type of a place when hiking a couple weeks ago.

There is a reasonable chance it would be the case. After all we did find some of our degraders at locations of high general biodiversity, rather than strictly from graveyards afterall.

However the thing about most animals is that they don't live that long, and they don't accumulate many of these very slowly accumulating substances to anywhere near the degree we do.

[caston]

Do you guys use any online enzyme databases to help with this project?

For example:
http://www.brenda-enzymes.info/
http://metacyc.org/
http://us.expasy.org/enzyme/

[eternaltraveler]

yes

[caston]

Can you use enzymes against skin cancers?

Sorry if that's getting offtopic but I'm only just starting to understand how cool enzymes are.

[Luna]

Wouldn't it be really complicated?
The enzymes need to detect specific cells.

[caston]

do most cancer treatments *actually* do that?

Of course Lyso-SENS doesn't address nuclear mutation does it?... so we should try to get back on topic

[soren]

Gads! Im speeding up my studies as fast as I can!
Fueled by HGH and the terrors of a misspent youth, I sincerely hope some day to partake of these studies...
Yes, and indeed, grave-soil robbing would be not the best PR for SENS...
However, if it can be done in stealth, from the deep soil by means of a push rod, is this of any use?