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Laser Ablation of Lipofuscin

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#151 AgeVivo

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Posted 10 March 2010 - 10:12 PM

explanation about why the research paused (change of activities by Nason, technical troubles with the method, other) would be nice, to know whether the idea should be pursued (e.g. by someone else in another lab) and if imminst should try promoting other research or not.

#152 Florin

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Posted 11 March 2010 - 01:24 AM

Sorry for not mentioning this earlier. The pages are not active right now because, due to unforeseen events the research had to be temporarily paused. I'll post more soon.


It has been over a week since I asked about this issue and more than two months have passed since Nason posted to his blog, but no answers have been posted in this thread. So, how soon is "soon?"

#153 AgeVivo

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Posted 11 March 2010 - 09:26 PM

It has been over a week since I asked about this issue and more than two months have passed since Nason posted to his blog, but no answers have been posted in this thread. So, how soon is "soon?"


on Nason's blog, **January 5th**:

Experiment 1 - Results
Sorry its taken me this long - lots of issues going on at once on my end. I can run the statistics if need be to try and determine significance - I'm looking up how to do it, since there are many complex factors, such as lost worms, environmental factors, etc. However, I think the trend is clear - there's some benefit with the most heavily-treated group, at least early on. Later, the effects of contamination make definitive determinations impossible. Replication with more redundancy and better control over environmental conditions is in order:

http://www.nasonschooler.com/research/docs/exp1.pdf


interesting; it is still ongoing???

Edited by AgeVivo, 11 March 2010 - 09:28 PM.


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#154 Anthony

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Posted 12 March 2010 - 01:17 AM

explanation about why the research paused (change of activities by Nason, technical troubles with the method, other) would be nice, to know whether the idea should be pursued (e.g. by someone else in another lab) and if imminst should try promoting other research or not.





I think that my donation to the fund was worthwhile even if we never hear anything else from Nathan because I believe that the experiment demonstrated the potential for further, more detailed assays on this topic. I think that is all one can really hope for with an initial, experiment--to show some correlation between lipofuscin and health. Granted, it would be nice to obtain some additional data from the lipofuscin research...

#155 Florin

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Posted 12 March 2010 - 03:05 AM

explanation about why the research paused (change of activities by Nason, technical troubles with the method, other) would be nice, to know whether the idea should be pursued (e.g. by someone else in another lab) and if imminst should try promoting other research or not.

I think that my donation to the fund was worthwhile even if we never hear anything else from Nathan because I believe that the experiment demonstrated the potential for further, more detailed assays on this topic. I think that is all one can really hope for with an initial, experiment--to show some correlation between lipofuscin and health. Granted, it would be nice to obtain some additional data from the lipofuscin research...

For $27k we should expect more than just a single contaminated experiment that has produced a somewhat questionable result. We should also expect a timely explanation of when more experiments will be performed. That explanation hasn't been forthcoming from anyone.

Also, I'm still not sure what purpose disabling access to the laser grant and research pages serves—even if it's only temporary. Anyone know and willing to share?

#156 Mind

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Posted 12 March 2010 - 11:20 PM

Sorry about the delay Florin and Agevivo. I was away for a couple days this week and just getting caught up. Here is a statement from the SENS Foundation:

The Immortality Institute and SENS Foundation would like to update the community about the status of research into the laser ablation of lipofuscin.

Research in this area, funded in large part by a grant from Immortality Institute, has been taking place at the SENS Foundation Research Center, in Sunnyvale, California, with Nason Schooler as principal investigator. Nason’s project was developed to determine the effect of laser ablation on the lifespan of a simple model organism (C. elegans), and to characterize the treatment within human cells.

Through the generous support of the Immortality Institute, and additional funding from SENS Foundation itself, definite progress has been made. SENS Foundation worked with the principal investigator to address many of the challenges which limited this progress over the life of the project – purchasing an optical table to remedy alignment instabilities, for example.

When work on the project at the Research Center came to an end, the Foundation conducted a scientific review. This covered both the project itself, and a proposal to continue with further (Foundation-funded) work. At this time the Foundation feels that the continuation of this project is not closely enough aligned with its SENS strategy to be a viable option for additional support.

Although the project is no longer a component of SENS Foundation’s research portfolio, the Immortality Institute proposes to continue, working directly with Nason, to re-start this research as soon as possible and reach a successful conclusion. SENS Foundation fully supports this initiative.

SENS Foundation has offered to allocate a larger sum from its own core funding to cover the amounts spent to date on the project, effectively reducing the amount of Immortality Institute grant funding used. This will allow the Immortality Institute to reallocate some of this grant funding either directly, to Institute expenditure on the continuation of the project, or to a related project. SENS Foundation will also make the laser, optics, optical table, and other equipment available on loan for any continuation of the project.

The Board of Immortality Institute is working closely with the executive of SENS Foundation to finalize these operational details.



#157 Mind

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Posted 12 March 2010 - 11:33 PM

So here is what I would like to see happen:

1. Get Nason going again in a new lab. I have contacted Nason, he wants to get going, and will provide a detailed list of what he will need, as far as equipment goes.

2. SENSF will send any equipment that was used on Laser Ablation (previously) to anywhere we can get Nason set-up. Right now he is in Iowa. We will also determine how much additional funding will be needed from SENSF.

3. As far as experimental results go, we need a more statistically relevant worm result (maybe couple more trials), and then we need to see how human cells respond to the treatment. This is a minimum. Florin and others are correct that the results thus far are simply unacceptable.

I personally donated a few hundred dollars and a ton of time to this effort. I am determined to make sure we get some relevant data. I really want to find out if clearing out lipofuscin has a positive effect on the lifespan in a model organism. I want to know if lipofuscin can be safely removed from human cells with the laser treatment. Nason feels an obligation to the community. SENSF will help get things set-up again. This is only a minor setback. I urge everyone to focus on the future and work together.

#158 Ghostrider

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Posted 13 March 2010 - 02:53 AM

So here is what I would like to see happen:

1. Get Nason going again in a new lab. I have contacted Nason, he wants to get going, and will provide a detailed list of what he will need, as far as equipment goes.

2. SENSF will send any equipment that was used on Laser Ablation (previously) to anywhere we can get Nason set-up. Right now he is in Iowa. We will also determine how much additional funding will be needed from SENSF.

3. As far as experimental results go, we need a more statistically relevant worm result (maybe couple more trials), and then we need to see how human cells respond to the treatment. This is a minimum. Florin and others are correct that the results thus far are simply unacceptable.

I personally donated a few hundred dollars and a ton of time to this effort. I am determined to make sure we get some relevant data. I really want to find out if clearing out lipofuscin has a positive effect on the lifespan in a model organism. I want to know if lipofuscin can be safely removed from human cells with the laser treatment. Nason feels an obligation to the community. SENSF will help get things set-up again. This is only a minor setback. I urge everyone to focus on the future and work together.


Good to hear that there will be a second attempt. This comment raises some questions:

"At this time the Foundation feels that the continuation of this project is not closely enough aligned with its SENS strategy to be a viable option for additional support."

What do they mean by that comment? Do they feel that laser ablation of lipo is unlikely to succeed / produce results in humans? Or are they focusing all their financial support behind the one or two SENS strands most likely to reach market / produce results the soonest? I hope it's the second option and if so, I agree with their strategy. Given their amount of funding, I hope they focus their efforts on the SENS threads most likely to produce results the soonest. Once they have results, they will gain more credibility in the scientific community (not to say that they don't have credibility currently)...the investment community likes to see promising results first regardless of how noble or good the idea sounds.

#159 Florin

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Posted 13 March 2010 - 04:51 AM

Thanks for the update Mind!

If the research will continue (which at the moment seems that it will) with better quality control and timely news updates, I have no further concerns.

The reason why the SENSF isn't supporting the project anymore is probably due to the their desire to focus on a just few core projects but confirmation would be nice.

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#160 Shannon Vyff

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Posted 13 March 2010 - 08:58 AM

I had the idea SENSF was trying to be more effective in what they support by focusing on a few core projects (my idea is that they are choosing projects that can end the aging mechanism versus treat it-as much as possible). I think our supporting laser ablation of lipofuscin with Nason's ongoing work is the best use of the money we've already put into it, and that although there is not enough evidence nor has it been compiled properly-there is still some indication that this project can be of use--if even as radical treatment. Regardless, more data should be collected to give a better idea as to laser ablations' effectiveness.

#161 Mind

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Posted 13 March 2010 - 01:18 PM

To answer Ghostrider: From what I gather, right now SENSF needs to spend their limited funds on other "core" projects that have been going on longer and are at a critical stage in development.

#162 Florin

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Posted 16 March 2010 - 08:06 PM

To answer Ghostrider: From what I gather, right now SENSF needs to spend their limited funds on other "core" projects that have been going on longer and are at a critical stage in development.

This seems to imply that the Laser Ablation of Lipofuscin project wasn't fully funded to begin with or am I missing something?

#163 Mind

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Posted 16 March 2010 - 09:07 PM

I can't speak with authority on the matter, but from my limited knowledge, in the beginning, SENSF was dedicated to seeing it through to completion. Poor macro economic circumstances and tight funding forced them to make some tough decisions about what core projects to continue at the Research Center. Again, this is just my "outsider" assessment, after talking with SENS and Nason.

#164 AgeVivo

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Posted 16 March 2010 - 09:47 PM

Hmm... how long will it take to set up everything again? I don't know the details, but if Nason can continue from where we stopped the experiment, it seems it would be easier. Unless he couldn't continue there for some technical troubles, i don't know

#165 Inkstersco

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Posted 19 March 2010 - 11:28 AM

Many thanks to Imminst for keeping this going. 

I always had a good feeling about the laser project, and was sad when priorities knocked it off the agenda. It's such a novel approach; It's like a SENS within a SENS. I'm heartened that Nason is determined to continue also.

And yes, we need decisive results, one way or the other.

--Iain

Edited by Inkstersco, 19 March 2010 - 11:29 AM.


#166 Mind

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Posted 28 April 2010 - 07:00 PM

This is the latest information from Nason: He expects the earliest he can pick this up again is September. I am going to suggest to the Board that they request money back from SENS (the amount that was not spent according to the original proposal) and keep it "in the bank" until the time arrives when Nason can pick it up again.

Like Iain, I too have a good feeling about the information that can be gained through this research. Even if there is no direct applicable treatment for humans, we will learn something valuable about how the destruction of lipofuscin affects a model organism and human cells.

#167 AgeVivo

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Posted 02 September 2010 - 09:20 PM

He expects the earliest he can pick this up again is September

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#168 Mind

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Posted 02 September 2010 - 09:45 PM

He is ready to start-up again. From what I heard from the Board, they are now looking for someone in his area (Iowa) who can perform oversight of the project.

#169 Nason

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Posted 20 November 2010 - 06:29 AM

OK all - it looks like I will be starting up the first of the year (Jan 2011) with minimal facilities in my basement lab. The plan is to spread the remaining 4 months out to 8 months (half time) to allow for more worm lifespan assays. Here is the basic agenda for the remainder of the project:


1) Test the effect of 8ns pulses on worm lifespan, at many different intensities. I suggest we go this route, as monkeying with the beamsplitting/mirror setup to get a pulse train created a nightmare of coherence problems - God knows what was actually hitting the worms when all was said and done; my beam profile looked like the man in the moon. The beam coming straight out of the laser has terrific coherence and a nice tophat profile, which although it is 8ns, which is a little harsh, it is wonderfully consistent, great at destroying pigments, and we can rest assured that all worms on the slide are getting the exact same exposure every time.

2) Examine effect on worm activity/livelihood. Since the worms grow distinctively and progressively less active in the 2nd half of their life, this can be used to roughly assess quality of life changes; i.e. if worms are all dying at the same time, but at 75% lifespan, laser-treated groups are still quite active, this could be seen as a definite extension of useful lifespan.

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500 (SENS purchased such a scope and Lorenzo tells me it is crude, yet passable, and useful for experiments (i.e. good enough to get some consistent data). Or better yet, get SENS to let us borrow their scope. Last I heard Lorenze said they were using another one in somebody else's lab, since it was so much better, so the one SENS bought may be sitting in a corner gathering dust somewhere. Not sure what our relationship with SENS is like these days, however; or if they will be using the scope for other stuff...

4) Assess the effect of laser treatment on a more long-lived strain of worms (such as DAF-16 mutants), as well as the wild-type. This could provide useful clues as to what is going on, whichever way the results go.


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#170 EmbraceUnity

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Posted 20 November 2010 - 09:04 AM

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500 (SENS purchased such a scope and Lorenzo tells me it is crude, yet passable, and useful for experiments (i.e. good enough to get some consistent data).


Is there a hackerspace near your location? You may be able to find some help building it.

http://hackerspaces.org

#171 Nason

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Posted 20 November 2010 - 02:11 PM

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500 (SENS purchased such a scope and Lorenzo tells me it is crude, yet passable, and useful for experiments (i.e. good enough to get some consistent data).


Is there a hackerspace near your location? You may be able to find some help building it.

http://hackerspaces.org


I looked, and there is one in town here. I'm not sure how much work it would really take though, so having extra hands, woodworking equip. etc. might not be that necessary. It would probably be too dark for taking images - probably something I would keep monkeying with on the side to see if I could get something to work...

#172 AgeVivo

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Posted 20 November 2010 - 06:05 PM

It's great that you are back. And you seem to be quite well prepared. Do you need specific contacts for people who know specific techniques that you are a bit discovering?

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#173 Nason

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Posted 30 November 2010 - 05:52 PM

Thanks. :) I am familiar with all the techniques I will be using to start with - if we actually get the equipment to do fluorescence, and people have input on how to best detect lipofuscin in worms, that would be great. Murakami has done this quite a bit, so he would be a great source too, if I can track him down. Last I heard he was in California somewhere...

John Schloendorn has graciously volunteered to oversee the project in any way needed. I am also able to start in December (like tomorrow) if that would be beneficial - it seems there was some concern about waiting until January? A December start would be great, as I could get equipment and worms on the way right now, so we would be ready to start actual experiments before Christmas.

So, as soon as I get funding I will order stuff and get things rolling.

Nason

It's great that you are back. And you seem to be quite well prepared. Do you need specific contacts for people who know specific techniques that you are a bit discovering?



#174 John Schloendorn

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Posted 01 December 2010 - 01:41 AM

John Schloendorn has graciously volunteered to oversee the project in any way needed.

No I have not.

Rather, I have pointed out that I am not in the area, and feel that any "oversight" worthy of the name is not possible remotely.

I have offered to make a statement that in my judgement there is no risk of unethical on incompetent behavior on Nason's part. I hereby make that statement.

This should not be construed as agreement to oversee the project in any way other than making the above statement.
However, if anyone has specific requests for me about what else I could do, I will be glad to hear them out.

#175 Nason

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Posted 01 December 2010 - 06:12 AM

John Schloendorn has graciously volunteered to oversee the project in any way needed.

No I have not.

Rather, I have pointed out that I am not in the area, and feel that any "oversight" worthy of the name is not possible remotely.

I have offered to make a statement that in my judgement there is no risk of unethical on incompetent behavior on Nason's part. I hereby make that statement.

This should not be construed as agreement to oversee the project in any way other than making the above statement.
However, if anyone has specific requests for me about what else I could do, I will be glad to hear them out.


OK, thanks for the clarification John. :)

#176 NasonSchooler

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Posted 13 December 2010 - 01:31 PM

(I just changed my account so I could log in via facebook. hope this doesn't cause too much confusion...)

Here is the proposal for the latest plan on how to tackle the remainder of this project in 2011:

* Stick to the 4-month schedule

* Month 1 I will get all necessary equipment that I don't already have ordered for standard lab/worm work, get my worm plates ordered and poured, order worms, get synchronized cultures going, start preliminary/calibration assays with worms.

* By beginning of month 2 I will have enough extra to purchase a fluorescence scope. I'm going to be spending slightly over $2000 on the fluorescence scope - this will be all of month #2's salary + some of the equipment budget. I plan to sell the scope at the end of the experiment to recoup most of the expenditure.

* By then everything will be ordered and set up, and the first preliminary worm/laser lifespan/viability assays begun - primarily to make sure everything is running smoothly

* Month 2 will consist of an initial battery of fluorescence assays on worms of different ages to determine best (apparently) safe levels of laser power for pigment destruction, and the continuation of lifespan/viability work

* Months 3 and 4 will be the main 'best shot' lifespan and viability studies, based upon previous data

Cell culture work is not going to happen with the facilities currently at my disposal. That just means more worm work - and with worms, the more runs and the more numbers, the better the statistical power of the results.


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#177 AgeVivo

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Posted 13 December 2010 - 02:03 PM

8ns, which is a little harsh

by curiosity, what do you think would be better than 8ns?
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#178 AgeVivo

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Posted 13 December 2010 - 02:05 PM

purchase a fluorescence scope. (...) sell the scope at the end of the experiment

does this mean it wasn't practical to borrow a fluorescence scope from sens' lab, or another lab?
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#179 NasonSchooler

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Posted 21 December 2010 - 08:00 PM

8ns, which is a little harsh

by curiosity, what do you think would be better than 8ns?


200ns

Edited by NasonSchooler, 21 December 2010 - 08:00 PM.

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#180 NasonSchooler

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Posted 21 December 2010 - 08:01 PM

purchase a fluorescence scope. (...) sell the scope at the end of the experiment

does this mean it wasn't practical to borrow a fluorescence scope from sens' lab, or another lab?


yep.
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