67 replies to this topic

[Mind]

Legitimate bio-marker testing is important to our community to help determine what current approaches are the best for slowing aging

 

It is 2018, and I can't believe how many anecdotal placebo-driven reports populate the LongeCity forum. Here is one egregious recent example if you want to chuckle: http://www.longecity...-human-history/

 

There was a budgeted effort to promote legitimate bio-marker testing last year, but it required members to pay for their first test, before embarking on an anti-aging regimen, where at the conclusion of the regimen time period, LongeCity would pay for a second test.

 

I am proposing a simpler approach. Here is the outline:

 

1. LongeCity pays for a standard aging-biomarker test. The most cost effective, easy to implement, and robust test available today is probably DNA methylation. LongeCity has a current relationship with Osiris Green and their test is the cheapest on the market, however, the standard deviation on their test is +/- 5 years. I have spoken with ZYMO and they will offer their test "at cost" for an effort such as this. ZYMO is HIPPA compliant and their standard deviation is only +/- 1.7 years.

 

2. We aim to offer this as a member benefit and to engage other communities such as the calorie restriction society.

 

3. Test subjects can opt to remain anonymous.

 

4. A simple questionnaire accompanies each test. This would ask each subject to rank their general approaches to life extension. Supplements, Diet, Exercise, Other. Depending upon the response, we could drill down further into regimens, but I would want to keep it simple at first to ensure a larger response.

 

5. We aim to complete the study before the end of Summer 2018, and present findings at RAADFest in September.

 

6. Stretch goal: Have a small number of people do DNA methylation testing at 3 different times of day. It is currently unknown if there is inter-day variability in DNA methylation.

 

7. Perhaps work in conjunction with newly formed OpenCures to complete and promote the study.

 

8. If successful, continue with testing on an annual or semi-annual basis. preferably with the same study participants.

 

Drawbacks/Objections

 

1. There are already a lot of groups (example: patients like me) that share test data, and there are many studies involving aging bio-markers. However, I am unsure that there are any studies that have easily accessible data AND focus upon longevity activists.

 

2. It is unlikely that a small study of a few dozen people will produce statistically valid results. To me, that is okay. We WILL learn something and I am certain there will be incredible marketing and community-building opportunities with such a study.

 

3. Cost. 5-10K, maybe higher if we can get some other groups to promote the study or if we can use other crowd-funding platforms. With 10K we could test between 50 and 75 people.

 

Leadership: I would be lead organizer and promoter.

 

LongeCity certainly has the budget for such a study and has enough connections to get a good number of people involved. LongeCity has not done much of consequence as of late. This could be a solid effort to help the community, not only functionally (what regimens work), but also as a promotional effort (life-extensionists are younger and healthier). 

 

 

Legitimate bio-marker testing is important to our community to help determine what current approaches are the best for slowing aging

[YOLF]

I'm all for this. Count me in. I have a fairly comprehensive regimen and I'd love to see what kind of biomarkers I can show off.

 

Can we just fundraise this on indiegogo oslt?

 

As a side note, biomarkers on a whole are somewhat limited. I think we should expand this to include a variety of markers. We've funded 20-30k research projects before and the M Foundation or M Prize is more interested in seeing human results these days. Perhaps they'll match us and advise on what we should look to test. I suggest that we first select which members are going to be tested with an application process that inquires as to the methods and goals of the individuals otherwise we may not find what we're looking for or put on display just how many things can be done. There is a complex landscape of possibilities. Even worse, we could wind up discrediting perfectly valid methods without adequate testing and actually waste money discrediting ourselves. To that point I suggest we work out sponsorships for as many different kinds of aging tests as possible and apply them where feasible from the budget. Supplement companies would sponsor individual members as they graduate from the LongeCity program. Though they needn't leave entirely, rather they could take on different roles.

 

So from a top down perspect, I'm proposing that we do this:

1. Make this a yearly fundraiser and sponsorship (for testing) drive
2. Take applications from prospective community members for review by a board of scientists and sponsors which will exclude those involved in selling supplements. Accept applications based on the novelty or chance of success of the goal and match them with the appropriate tests.
3. Make it something of a rejuvenation/biohacking pageant/competition and aim to celebritize the highest performers as well as get them sponsored the way body builders or race teams would be (they can use a pseudonym and live a Hollywood "double life" if they wish to remain anonymous, but they should still be willing to promote the movement). As public figures, they'll be able to further promote and advocate for our cause and help the program attract more sponsors.
4. Aim to aim high, this could become something big!

Edited by YOLF, 08 February 2018 - 02:04 AM.

[Droplet]

As long as I'd remain anonymous, I'd do a DNA test to aid research. I don't yet have any sort of regimen but I'm informed that I have some longevity-related genes. I do exercise regularly so that's something. If my DNA can help the cause somehow and it is all easy enough for me to understand, I'd be up for contributing to the cause.

[Adam Karlovsky]

I'll start by declaring my vested interest - I've recently joined a new medical consulting group with another member, Dr Attila Danko, as a research assistant and I guess also as an administrative coordinator. Our business is aimed at treating treatment-resistant health disordered patients (such as those with mood disorders, chronic pain, chronic fatigue, cognitive decline, etc) and secondly we're running an anti-aging / hedonistic-enhancement project for healthy clients. We currently have 2 clients lined up for the second service. In fact, this is why I have been absent on the forums lately, because I've been focusing on my work here in Australia.

 

This would be great for startups like us, and I'd hope there are other groups like us working on these projects in parallel. I'd love to co-operate rather than compete, it's just my nature.

 

I'd be interested in enrolling all enhancement project clients in something like this. Not having sought venture capital funding, the prohibitive costs of various tests is probably one of the big issues holding back the depth of the service, and the funding would be much appreciated by both our group and our clients.

 

We would only be working with clients at a pace we can reasonably handle, so the number of clients taking part in something like this would be at a dribble's pace. I won't even estimate how many people each year might enroll in the enhancement service, but I'd be confident that each case-study should provide valuable, anonymized, open-source data for the personalized protocols we have them follow.

 

So, based on the position I'm in, I am super excited by the idea and fully support it. While I would want to minimize the red-tape which will burden the process (and our enthusiasm), of course I'm on board with quality control standards and independent bodies offering recommendations and review.

[QuestforLife]

There are probably a fair few people who already pay for their own testing of various sorts, and might be willing to share the information. I for example took a Zymo mydnage epigenetic age test last summer and will be taking another one this summer. Perhaps we could start a database for people to register results and what supplements and lifestyle habits they followed. Another possibility is Longecity could offer to pay for tests if a member was willing to follow a certain regime for a set period. Just some ideas.

[kevin]

Hello fellow travellers, 

 

It's been a long time since I've come to the forums and commented and apologize for my long absence, but I intend to be here a bit more frequently and hopefully connect with many of you and discuss those things we can do to minimize the time to the development of interventions in aging. 

 

One thing is crystal clear from my experience, we need to come together as a community and really put our resources in one pot/pool, both financial and intellectual, if we are going to minimize that time, anything less is going to be suboptimal. 

 

What is needed is new data.

 

 

Without new data (whether newly generated, or just newly shared data that used to be hidden), nothing changes, and once that data is generated it needs to be analyzed with purpose.   Once in a blue moon, a tangible benefit may emerge from the analysis in the form of products or services, however the analysis will almost always lead to insights that will form iteratively better hypotheses to test or tell us that the avenue of inquiry is no longer worth pursuing. 

 

 We need to speed this cycle up to its maximum by freely providing the data, analysis and resources necesary to make it work. 

 

Justin is right, there are ton of efforts going into "measuring biological markers" with many entities, academic and corporate, but most of them are doing it for reasons other than minimizing the time to the development of aging interventions.   

 

LongeCity (formerly for me, Imminst) is an entity that deserves to have a place in the emerging landscape as a major contributor to the progress being made.   I have been talking with Justin and Caliban for years about how to make things go faster and I think a solution is emerging, and it will require all those of good will and rationality to participate for the right reasons.   Over the next while I will be describing an evolving effort which will allow everyone to contribute meaningfully to a non-profit/for-benefit hybrid entity which will be purpose built to accelerate the health technology development pipeline.  It will be supported by those who understand its Mission and the role they need to play and who want to be engaged in this effort. 

 

A hundred thousand people died horribly today.  Another hundred thousand tomorrow.   My parents are reaching the limits of average lifespan and I'm no spring chicken either.   We are all under the same scythe and it is difficult to say when you shall be reaped, but one thing is certain, if you don't put some energy into the development of health technologies, you may be surprised to find you or your loved ones facing an age-related challenge you didn't expect.. but when do we?   Thanks for listening and here's to working together for healthier longer lives.   

More to come. 

Edited by kevin, 10 February 2018 - 12:56 AM.

[ceridwen]

I already am facing an age related challenge I did not expect. Familial Alzheimer's! I was adopted and had no idea about this. Then I got my 23 and me results but by then I was suffering from decline. I really don't want to die.

[QuestforLife]

Ceridwen, to protect from Alzheimer's you need to be on rapamycin. Check out Alan Green's site (https://alzheimer-prevention.com)

[ceridwen]

Thanks

[ceridwen]

I was thinking that might be the wrong thing to be on if it is caused by CMV as I suspect. I need to find a way to destroy CMV before going on Rapamycin I think.

[QuestforLife]

CMV will make immune system senesce early, rapamycin prevents cellular senescence. Plus Alzheimer's is by far the bigger threat of the two and the one I'd be worried about if I was a APOE4 carrier.

For CMV just try and keep immune system healthy. Some people say BHT works so you could try that.

But Rapamycin is a must for APOE4 carriers.

(Moderators, feel free to move to a more appropriate thread!) Good luck!

[reason]

So beyond the simple one-off tests like Zymo's offering, I think there is merit in developing a general low-cost protocol guide for testing yourself.

 

I've been trying to put in some effort on this front, such as the testing section in https://www.fightagi...rug-candidates/ but currently it is in flux as I accumulate experience and all of my published comments are likely subject to later revision.

 

But if it was possible to at least haul out some generally useful approaches that don't cost much for the person in question, there's a lot of merit in propagating that as a standard - i.e. if you don't do [standard thing] then you're not really serious about what you are doing.

The quantified self community seems to have failed on this front; they're kids in a candy store, and don't follow through to the assessment of quality of methods. There isn't enough information out there on the degree to which different approaches are junk or not junk or are highly variable day to day or are hard versus easy to manage, and so on.

[sthira]

Legitimate bio-marker testing is important to our community to help determine what current approaches are the best for slowing aging...

I'm interested, and have been self-experimenting with long(ish) term CR attempts -- sometimes I'm mildly restricted (5-10%), sometimes I'm more deeply restricted (20-30%) -- and I've been doing this semi-obsessively for >7 years. For the past two years I've been hybridizing CR with monthly fasting-- loosely interpreting Valter Longo's work -- and documenting daily feeding behavior on cronometer.

1. LongeCity pays for a standard aging-biomarker test. The most cost effective, easy to implement, and robust test available today is probably DNA methylation.

Just throwing this out for consideration, but IGF-1 and IGF-BP3 might be interesting numbers to consider? Perhaps study participants could wash out of all interventions, eat an RDAish diet, then get a baseline blood test. Then we begin our own specifically-documented self-intervention, and blood test a few months later. Document everything, but first get baseline data for the win.

Blood tests might include a standard checkup with markers for insulin, CRP, white blood cell counts, coronary calcium scores, detailed telomere distribution evaluations... For males, free and total testosterone seems relevant. And how about glucose tolerance testing like OGTT?

2. We aim to offer this as a member benefit and to engage other communities such as the calorie restriction society.

That's an interesting idea since their forum is crickets. Al Pater's involvement would be interesting, and getting rockstars like Dean Pomerleau and Michael Rae on board would add fire and depth.

But the disappointing CR-ed macaque study results from several years ago popped many balloons -- does a CR Society even exist? Their president appears to be doing work Bill Faloon and LEF. Paul and Meredith of the "CR Way" fame might be interested in collaboration since they've spearheaded other studies, like a telomere study at UCSF several years ago. Collaboration with anyone(!) seeking anything(!) to slow aging -- as we drop our dogmas at the doors and seek the greater good -- would be really cool.

[YOLF]

I'd be interested in enrolling all enhancement project clients in something like this. Not having sought venture capital funding, the prohibitive costs of various tests is probably one of the big issues holding back the depth of the service, and the funding would be much appreciated by both our group and our clients.

 

For outside organizations, I think we should limit the number of entrants per org to get the best of the best and allow more people to participate. If the program expands, we could increase the number of entrants of course, but I think a primary goal here is to determine with higher certainty whether or not what our users is doing is making them physiologically and physically younger. We want to encourage as many of our members as possible to get involved.

 

Of course, if another org is footing the bill, it might wind up looking different, but for now we should assume it's just LC and out fundraising capacity. Let's build from there, otherwise I could see Hapi becoming the sole beneficiary before others have had a chance to apply.

[YOLF]

*Abstains from usual CR counterargument.*

[Droplet]

I already am facing an age related challenge I did not expect. Familial Alzheimer's! I was adopted and had no idea about this. Then I got my 23 and me results but by then I was suffering from decline. I really don't want to die.

 

That's horrible and I'm sorry to hear that you have this cruel disease. :(

[ceridwen]

My Homocysteine was 12 when last measured and my blood sugar is high. I clearly have insulin resistance

[Mind]

There are probably a fair few people who already pay for their own testing of various sorts, and might be willing to share the information. I for example took a Zymo mydnage epigenetic age test last summer and will be taking another one this summer. Perhaps we could start a database for people to register results and what supplements and lifestyle habits they followed. Another possibility is Longecity could offer to pay for tests if a member was willing to follow a certain regime for a set period. Just some ideas.

 

Thanks for the suggestion. LongeCity tried a program like this last year, but there was little interest. My feeling is that we need to lower the bar to get more people interested/larger numbers in order to get into the range of statistical significance - ie. make it very cheap and simple for people to participate. A single test with a simple questionnaire (at least to begin).

 

You bring up a good point though: For people who have already taken the a ZYMO test, it would be great if they were willing to share their results, (anonymously or not). More participants means a greater chance of discovering something valuable within the data.

[Mind]

So beyond the simple one-off tests like Zymo's offering, I think there is merit in developing a general low-cost protocol guide for testing yourself.

 

I've been trying to put in some effort on this front, such as the testing section in https://www.fightagi...rug-candidates/ but currently it is in flux as I accumulate experience and all of my published comments are likely subject to later revision.

 

But if it was possible to at least haul out some generally useful approaches that don't cost much for the person in question, there's a lot of merit in propagating that as a standard - i.e. if you don't do [standard thing] then you're not really serious about what you are doing.

The quantified self community seems to have failed on this front; they're kids in a candy store, and don't follow through to the assessment of quality of methods. There isn't enough information out there on the degree to which different approaches are junk or not junk or are highly variable day to day or are hard versus easy to manage, and so on.

 

Thanks for the input Reason. I did not mention it in the beginning, but I would hope that this would become a continual/annual effort. LongeCity has a stable enough income to keep this rolling for a few years.

 

That being said, it will be hard to define a standard because our knowledge of aging and aging-biomarkers changes, sometimes dramatically, from year-to--year. I am suggesting DNA methylation because it has the the greatest likelihood of being relevant based upon our current knowledge and it is relatively cheap.

 

The basic "protocol" I hope to develop here is that annual testing is IMPORTANT and that results/data should be open to everyone (even if some participants remain anonymous). LongeCity and other rejuvenation-promoting organizations should lead the way in regular testing and updating tests base upon the latest science.  Maybe we start with DNA methylation but migrate to something more comprehensive in the future (as long as it is financially viable).

Edited by Mind, 13 February 2018 - 07:20 PM.

[Mind]

 

I'm all for this. Count me in. I have a fairly comprehensive regimen and I'd love to see what kind of biomarkers I can show off.

 

Can we just fundraise this on indiegogo oslt?

 

As a side note, biomarkers on a whole are somewhat limited. I think we should expand this to include a variety of markers. We've funded 20-30k research projects before and the M Foundation or M Prize is more interested in seeing human results these days. Perhaps they'll match us and advise on what we should look to test. I suggest that we first select which members are going to be tested with an application process that inquires as to the methods and goals of the individuals otherwise we may not find what we're looking for or put on display just how many things can be done. There is a complex landscape of possibilities. Even worse, we could wind up discrediting perfectly valid methods without adequate testing and actually waste money discrediting ourselves. To that point I suggest we work out sponsorships for as many different kinds of aging tests as possible and apply them where feasible from the budget. Supplement companies would sponsor individual members as they graduate from the LongeCity program. Though they needn't leave entirely, rather they could take on different roles.

 

So from a top down perspect, I'm proposing that we do this:

1. Make this a yearly fundraiser and sponsorship (for testing) drive
2. Take applications from prospective community members for review by a board of scientists and sponsors which will exclude those involved in selling supplements. Accept applications based on the novelty or chance of success of the goal and match them with the appropriate tests.
3. Make it something of a rejuvenation/biohacking pageant/competition and aim to celebritize the highest performers as well as get them sponsored the way body builders or race teams would be (they can use a pseudonym and live a Hollywood "double life" if they wish to remain anonymous, but they should still be willing to promote the movement). As public figures, they'll be able to further promote and advocate for our cause and help the program attract more sponsors.
4. Aim to aim high, this could become something big!

 

 

If a LongeCity grant is not secured, then I would suggest maybe a crowd-funding route. Ideally, we would have a base grant from LongeCity and an additional matching grant.

 

As far as recruiting people ahead of time, I don't think that is necessary, but I could be wrong.

 

As far as many of the other points you raise, all interesting, but in order to get this off the ground, I maintain it has to be quite simple to begin with. Other modalities can be added/investigated in the future, based upon the success of this original effort.

[YOLF]

Ok, we'll keep it simple. What about a membership blood drive? I'm a little hesitant at this idea as there is a risk, even if small, of someone creating life from my blood stem cells as such has been shown to restore fertility... But I think the type of blood donation matters, we just need to make sure we're informed, I wasn't last time I went to donate. So maybe we can work something out with a blood donation company that shares their blood test data with the donor? Iirc, there are a variety of tests that get run to make sure the blood is suitable for donation. Perhaps they might have something useful?

[ceridwen]

I was wondering if I could have an Alzheimer's test? I think there might be 1 coming out in June. However I'm taking oragano oil and apple cider vinegar and actually think that at long last I'm seeing good results

[caliban]

Mind has reflected on many of the potential benefits and limitations of this idea. Based on these the financial scope suggested seems doable if there are no competing budget items in the 2018/19 plan. I'm unsure about the cost breakdown and would need more information. I don't anticipate a huge take-up, a survey to gauge interest might be useful.  

 

I don't anticipate scientific insights at this stage and see this more as a promotional initiative encouraging people to reflect on their biomarkers and getting them engaged in community discourse and into a citizen science mindset. Consequently I would frame this strictly as a 'Members perk' and not a crowdfunding candidate. I don't think it can be offered on an annual basis though. 

 

Experience teaches us that the momentum of any LongeCity initiatives depends less on the generosity of the funding (or even the impact on our mission) and more on the commitment of the project leader. Hence Mind's willingness to lead the project is salient, but I'd be concerned about impact on his other work. A partnership with opencures may be useful. I don't see us subsidising a commercial venture. 

[Adam Karlovsky]

What do people think about GlycanAge as a measure of aging? Without financial support we were going to cross-validate biological age by having clients/participants do an Osiris Green and a GlycanAge test every 6-12 months.

[YOLF]

Those sound like interesting candidates. Accuracy for Osiris Green doesn't look to be as high as the one Mind was talking about, but it does have a $65 price point, so more people could adopt using it assuming the other one is significantly more expensive. Glycan Age requires your doctor to sign up... good luck there... everyone is always asking their doctor to sign up for and learn this and that new thing and they need to make money, there's alot of competition for their time that competition adds cost to the diagnostic test. The service would need to be direct or we would need a telemedicine doctor to request it for our members oslt. I think that is another big hurdle for community testing. GlycanAge is also UK only.at present, though I guess being from AU or NZ, they've agreed to make exceptions?

Edited by YOLF, 14 February 2018 - 04:05 AM.

[QuestforLife]

My main worry about using an epigenetic aging test is: 1) it's insensitive to most interventions, i.e. only slowed for CR or rapamycin; 2) counter indicated for some interventions, i.e. any growth stimulants will accelerate it, even if they improve health; and 3) does it actually have an relevance to aging? It measures a small selection of genes' methylation states, which is okay for a clock, but these genes don't seem important to aging in themselves.

 

Not saying we shouldn't use it, I do, but it's certainly not the be-all-and-end-all.

[YOLF]

My main worry about using an epigenetic aging test is: 1) it's insensitive to most interventions, i.e. only slowed for CR or rapamycin; 2) counter indicated for some interventions, i.e. any growth stimulants will accelerate it, even if they improve health; and 3) does it actually have an relevance to aging? It measures a small selection of genes' methylation states, which is okay for a clock, but these genes don't seem important to aging in themselves.

 

Not saying we shouldn't use it, I do, but it's certainly not the be-all-and-end-all.

 

Hmmm... how many genes does it measure epigenetics for? I was thinking it was a complete test. But if indeed the results of better test results are youthfulness, then I think we've got something good. 

 

Like Mind said, we have to start small, it won't be a be all end all test as to the success of our methods and we may just be looking for a diamond in the rough if we aren't giving it to people with related targets as part of their supplement regimen or large supplement regimens that can affect multiple systems. The best we can do is be very educated as to the what the test results mean by the time the second test comes through.

[Johnny Adams]

Justin – This excellent idea will provide valuable objective measures of various therapies and methods, and hopefully make members aware of some new therapies.

 

LongeCity members – I’m helping Justin with this, and look forward to becoming more active in the LongeCity community in the future.

[YOLF]

Great to have you!

[Mind]

My main worry about using an epigenetic aging test is: 1) it's insensitive to most interventions, i.e. only slowed for CR or rapamycin; 2) counter indicated for some interventions, i.e. any growth stimulants will accelerate it, even if they improve health; and 3) does it actually have an relevance to aging? It measures a small selection of genes' methylation states, which is okay for a clock, but these genes don't seem important to aging in themselves.

 

Not saying we shouldn't use it, I do, but it's certainly not the be-all-and-end-all.

 

All valid concerns. Considering that our knowledge of aging and aging biomarkers is accelerating and changing, and that there is no "gold standard", we end up having to just start somewhere. DNA methylation seems to be the best intersection of simplicity, cost and knowledge (about aging).

 

The main concern at this early stage is to promote a culture of objective testing/evidence.

 

I strongly suggest one company and one test to begin with. Adding additional tests (possibly from different countries) adds significant data handling difficulties.

 

We need to set a solid foundation, learn how to smoothly complete a study such as this, and then perhaps move on to more expansive testing in the future.