36 replies to this topic

[Steve H]

Opinion is divided on the role of Telomeres in aging though short Telomeres are shown to lead to dysfunction and disease. There is an opportunity to put the power of Telomeres to the test in people via AAV gene therapy a technology which has improved rapidly in terms of accuracy and safety and is available to us now.

 

Studies by M Blasco et al and others have indicated Telomere therapy can restore function to tissue but so far no one has taken this to the human model due to unproven concerns about Cancer. There are however studies that suggest optimum Telomere length in fact offers some level of protection rather than encouraging Cancer and that short Telomere's are more likely to lead to Cancer.

 

Studies by Shay and Wright also demonstrate that Telomere's regulate gene expression via the Telomere positing effect which leads to epigenetic drift as gene expression changes and silenced genes are expressed as they shorten.

 

Dr Helen Blau also this year demonstrated a technique that rejuvenated human skin and muscle Telomeres by about 10% in-vitro allowing them to resume division and continued function. 

 

It is not the only factor involved in aging but IMO it has a key role to play in aging. The big question is should we continue to sit on the fence or should we take the step and try a limited test in-vivo to see if the beneficial effects seen in other animals apply to people too? 

[ceridwen]

of course we should

[YOLF]

Just got a reply from them, looks like they're doing it only for those in dire need. So if you aren't dying of something, you can't get it. It's also a bit on the expensive side. Probably well within range of the wealthy though. We'll need to see it come down in price though. TA65 was $35k a few years ago, not it's as little as $1200 a year or even $480 for generic alternatives. It's just a matter of time. 

 

I had a conversation with AgeViVo a few months ago and he was very positive on the efficacy/accuracy of CRISPR applications. I imagine the first few patients here will see some great results and get this thing kickstarted for us. 

 

They expressed an interest in raising funds to start experimenting with some other genes that I brought up. Perhaps we could a LongeCity fundraiser and see if we can't help them get the technology closer to implementation.

[Steve H]

A fund raiser would be good. My personal preference would be hTERT to once and for all end the debate over Telomeres and their ability to rejuvenate. It could be tested with another therapy in mice but in a person would IMO be the way to go and really push the boundaries on longevity research.

[niner]

Just got a reply from them, looks like they're doing it only for those in dire need. So if you aren't dying of something, you can't get it. It's also a bit on the expensive side.

 

How much are they charging for a course of therapy?  If it's experimental, shouldn't it be free?  Do you actually have to be dying in order to get it?  If so, maybe that's so that if it gives you some horrible disease, they can say "well, he was going to die anyway..."

 

The way things like this are often tested is to look at them not only in mice, but also various other animals.  Primates are the most expensive, but are the closest to humans.

 

Maybe they can find dying people for which telomere extension might actually be therapeutic.  I'm not sure what condition that might be-- heart failure, maybe?

[Steve H]

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

[niner]

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

 

Who are these guys, anyway?  Where is this happening?

[zorba990]

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

You don't realy want long term myostatin suppresion because that seems to produce tendon issues. So have they somehow solved that issue?

[YOLF]

 

Just got a reply from them, looks like they're doing it only for those in dire need. So if you aren't dying of something, you can't get it. It's also a bit on the expensive side.

 

How much are they charging for a course of therapy?  If it's experimental, shouldn't it be free?  Do you actually have to be dying in order to get it?  If so, maybe that's so that if it gives you some horrible disease, they can say "well, he was going to die anyway..."

 

The way things like this are often tested is to look at them not only in mice, but also various other animals.  Primates are the most expensive, but are the closest to humans.

 

Maybe they can find dying people for which telomere extension might actually be therapeutic.  I'm not sure what condition that might be-- heart failure, maybe?

 

The therapies are used under compassionate care guidelines. Everything I wanted had a 6 figure price tag. I imagine that once they've purchased their building and built a lab as they intend to that the price will come down substantially. But they didn't say what kind of impact our fundraiser might have. Obviously there is a long way to go make substantial improvements in price. They're looking to raise $1M for the lab/facility and then they'll need operating costs. $250k would be enough to talk about getting trial results on atherosclerosis. That's still pretty big for as much as we've raised so far, but I think a bigger goal merits a higher fundraising capacity. We could probably do it in $25k goals on IGG. A gofundme can run indefinitely, so we'll have plenty of time if we went that way. 

 

I suppose we could arrange for some primate studies if we can find a group of them that are going to die imminently, but I don't think they're looking to research on anything but humans and waiting for primate studies won't save people immediately. Imagine being in the end stage of cardiovascular disease with pipets for arteries or realizing you have dementia. They have a weight loss therapy too, not sure where that would become compassionate care though. But that's probably why they're in Mexico and doing what they do under compassionate care guidelines. I think their first customers will probably be rich cryonicists who are facing the freezer or other certain demise. Maybe non cryonicists who've run out of other options. 

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

Myostatin has been shown to remove atheroscleotic plaque? Sounds interesting, got a link to that one?

[YOLF]

A fund raiser would be good. My personal preference would be hTERT to once and for all end the debate over Telomeres and their ability to rejuvenate. It could be tested with another therapy in mice but in a person would IMO be the way to go and really push the boundaries on longevity research.

This would be a separate matter as I think they're looking for human trials. 

 

But yeah, an hTERT lifespan study would be nice. I'm thinking it could be done with fruit flies first and then mice or started concurrently so we have results sooner.

[YOLF]

 

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

You don't realy want long term myostatin suppresion because that seems to produce tendon issues. So have they somehow solved that issue?

 

I was under the impression that this claim of myostatin inhibition wasn't merited. Do the bully whippet, Belgian Blue, and Piedmontese?

 

It looks like reproductive issues are more the problem here. Less myostatin means bigger babies. Then there are some concerns with cardiac hypertrophy. Myostatin may be involved in keeping heart cells from getting too big. Cardiac myostatin is produced within the heart, so if their CRISPR can target just non cardiac tissue it could have some pretty good merits here. I'm wondering what the affinity of supplemental myostatin inhibitors are for heart muscle too... 

[zorba990]

They plan to test a combination of htert and fullostatin to increase muscle mass, rejuvenate cells and they believe their proprietary miyostatin inhibitor can also remove atherosclerosis plaques.

They could test it in mice but they are hoping to do a small localized test in humans ideally before moving into a full systemic Treatment. It's this small test I am hoping to support so we can see if it works. Would probably be localized skin for a small pilot study but that would need funding ofc.

You don't realy want long term myostatin suppresion because that seems to produce tendon issues. So have they somehow solved that issue?

I was under the impression that this claim of myostatin inhibition wasn't merited. Do the bully whippet, Belgian Blue, and Piedmontese?

It looks like reproductive issues are more the problem here. Less myostatin means bigger babies. Then there are some concerns with cardiac hypertrophy. Myostatin may be involved in keeping heart cells from getting too big. Cardiac myostatin is produced within the heart, so if their CRISPR can target just non cardiac tissue it could have some pretty good merits here. I'm wondering what the affinity of supplemental myostatin inhibitors are for heart muscle too...

Well I hope its proven untrue, however,

Tendons of myostatin-deficient mice are small, brittle, and hypocellular.
http://www.ncbi.nlm....pubmed/18162552


Myostatin blockers destroy tendons
http://www.ergo-log....tintendons.html

[YOLF]

Has tendon degeneration been demonstrated in adult models having had gene therapy? At this point I think there is still room for use as adults.

 

Creatine lowers serum myostatin and has a high affinity for muscles. It doesn't seem to cause tendon injury, but may limit range of motion for unknown reasons. 

 

I'm thinking the BioViva treatment would target select cell groups that would benefit from it and spare others. So tendon cells, so long as they aren't dependent on muscle myostatin would continue to have plenty of it if they do in fact need it to stay strong. Some good info leads on wiki, but not citations... 

 

I've been using creatine and myox recently. I have previously had minor tendon problems for which I did not seek medical care (frequent pain in the tendons when running that would leave me limping for a week or so). I think my solution has been to take glucosamine, MSM, boswelia, and krill oil, and to run in Crocs. Right now I'm just taking KO and using Crocs with no injuries or anything like that yet, though I do plan to start running on a track again. So this will be a good test of the myostatin inhibition results. I'm just getting through my 3rd bottle of MyoX and have one left to go. Presently trying to lose some of the creatine water weight though, but may cycle back on to it depending on results. Important to note is that I suspect my tendon problems are a result of levaquin, avelox, and more recently a day or two of cipro. Megadosing reduced glutathione and taking mimetics seems to help alot. I wouldn't be doing this if I thought it would be bad for me. 

 

Been eyeing up some ultrasound imagine machines that I would be able to take some measurements with and have an ultrasound appt. tomorrow. Maybe I can get my doc to look at my ankle while she's at it if I can remember it. Job interview tomorrow too. Home ultrasound imaging will be a wonderful thing.

[Steve H]

I understand the Fullostatin therapy they are using is the same as the one that is in phase III trials for Beckers Muscular Dystrophy at the Nationwide Children's Hospital currently. They just concluded phase II with some startling results in some of the patients in the six meter walk test, one patient walked an additional 129m after a few weeks of therapy! No mention of heart hypertrophy, I understand the therapy is in the same family group as GDF-11 and targets similar pathways. I am new so I cannot link the study but if you go to clincialtrials.gov and look up Nationwide Childrens Hospital Beckers MD the intial results for it are in, the study is focused on Beckers MD so it doesn't go into Atherosclerosis, Bioviva are saying it does effect plaques though. There is also some suggestion in other studies that Miyostatin inhibitors can effect Plaque so it is plausible this could be a side effect of targeting that pathway, according to them their CMO has used it and has no plaques according to an MRI scan he took. 

 

The AAV therapies they have use different Serotypes to target different cell types so they can isolate specific groups eg, skin cells etc...

 

hTERT is the really big one for me as it has shown so much benefit in animal studies since the 90s and has rejuvenated every human tissue it has been tested on in-vitro and yet has never been used in-vivo. The fear of Cancer has held its study back and yet if anything studies are showing longer telomeres in fact offer a level of protection against cancer and various other disease. I would cite a number of studies but again I am unable to link articles currently.

 

A full body therapy is as suggested is currently a six figure cost due to them needing to build their own manufacturing lab but the costs would dramatically fall once they 

 

A mouse or fruit fly study is possible and having spoken to them a mouse study using both gene therapies would be around 45k + 5k publication and research write up on top. That kind of figure I think it within crowdfunding reach but I believe they would prefer to test in people as they are more a bench to bedside company.

 

Big question is if you could only pick one of the therapies to do a small test in a person which would it be? hTERT or Fullostatin?

 

 

 

 

[Steve H]

@YOLF Miyostatin inhibition has potential to help with atherosclerosis and a number of studies have hinted at this. As I am new I cannot link to things but if you google Powen Tu 

Genetic Disruption of Myostatin Reduces the Development of Proatherogenic Dyslipidemia and Atherogenic Lesions In Ldlr Null Mice 

 

They conclude: Inactivation of Mstn protects against the development of insulin resistance, proatherogenic dyslipidemia, and aortic atherogenesis in Ldlr−/− mice. Myostatin may be a useful target for drug development for prevention and treatment of obesity and its associated type 2 diabetes and atherosclerosis.

 

The caveat is of course these are a mutant mouse strain but other studies have also hinted at mStn inhibition having benefits against formation of plaque and it being in the same family as GDF-11 may stop heart related hypertrophy, GDF-11 is currently being studied for that and other effects to it is possible as it targets similar pathways. We wont know though unless it is tested though BioViva says they CMO has tested it on himself and has MRI scans showing no plaques, not difficult to validate this claim either. 

 

Senescence in arterial smooth muscle cells also contribute to atherosclerosis so Telomere rejuvenation could also help mitigate the problem as well as potentially boosting internal repair mechanisms that reduce cellular waste.

 

I can certainly see why Bioviva is interested in combining hTERT and mStn inhibitors especially if it ablates plaque and the TERT rejuvenates the tissue, not hard to imagine the benefits being quite substantial if they work ofc. 

Edited by Steve H, 13 May 2015 - 08:47 AM.

[YOLF]

Thanks Steve, great bit of info.

[alc]

One thing is that behind BioViva is  Michael Fossel and at least for me, that sounds very promissing. I see him as a sharp mind with a good perspective on things.

http://www.michaelfossel.com/


Might be the case that telomerase therapies aren't offering the ultimate rejuvenation that we are all dream about, but I believe they offer lots of things to consider. Some recent studies show that going that path, things are promissing, and I'm refering to the new study from CNIO and the other recent studies.

 

CNIO scientists are able to take immortality from cancer

 

http://www.eurekaler...i-csa051115.php


TELOMERE CHANGES PREDICT CANCER

“Changes in chromosomes years before cancer diagnosis could yield biomarker to predict cancer”

http://www.northwest...ict-cancer.html


Telomere extension turns back aging clock in cultured human cells, study finds

https://med.stanford...ured-cells.html

 

 

Also, there is George Church that recently he mentioned that his team is hard at working on reverse aging using CRISPR/Cas9

 

“CRISPR: Genome engineering with a purpose”

http://casw.org/stud...neering-purpose

 

So I would say that BioViva is on the right track, and I really do hope that they bring in very good results as we all waiting on things to hit the market as oposed to

lots of promisses from lots of places.

 

Just that "six figure" treatments sounds sci-fi. In order to be affordable, they need to come down to a 10k figure or even less. Let's hope in couple years technology advances so much that indeed these treatments will cost 5k to 10k. I'm pretty much sure that selling to more people for less will bring them more profit that selling expensive to just few people. I do hope CRISPR/Cas9 will move very fast and encompass reverse aging as well.

[Steve H]

Dear alc et al,

The large cost is due to them not having a production facility but speaking to Liz she is very keen to get prices down to an affordable level. It is her hope that governments will work with her and potentially such therapy could be free ultimately, this is similar to how Aubrey de grey sees things as the savings in healthcare would make it viable.

The vector they want to use for tert is the same as Michael fossel wants to use only difference is they want to begin testing now not fifteen years time under the fda. They plan to launch an fda overseen offshore test this year which hopefully demonstrates safety and efficacy to them but is not restricted by red tape being in Mexico.

They could do a two gene therapy mouse study for $50,000 but are more interested in taking this to people. I think there are enough positive results from past studies to support this.

Question is can we help get a small localized skin test in people done to get the ball rolling?
Dear alc et al,

The large cost is due to them not having a production facility but speaking to Liz she is very keen to get prices down to an affordable level. It is her hope that governments will work with her and potentially such therapy could be free ultimately, this is similar to how Aubrey de grey sees things as the savings in healthcare would make it viable.

The vector they want to use for tert is the same as Michael fossel wants to use only difference is they want to begin testing now not fifteen years time under the fda. They plan to launch an fda overseen offshore test this year which hopefully demonstrates safety and efficacy to them but is not restricted by red tape being in Mexico.

They could do a two gene therapy mouse study for $50,000 but are more interested in taking this to people. I think there are enough positive results from past studies to support this.

Question is can we help get a small localized skin test in people done to get the ball rolling?

[Steve H]

Right a quick update. BioViva is interested in working with Longecity and is going to apply for funding for a pilot study with hTERT delivered to a patient using AAV gene therapy the same one Dr Fossel wants to bring to the FDA. Liz Parrish believes it would be a single patient pilot study for rejuvenation for this level of funding and it would be targeting skin cells on the face to the sub dermal level. Lets hope we can work with them and put this big question to the test, we have the chance for some really disruptive science should we take the dive?

Edited by Steve H, 21 May 2015 - 09:36 PM.

[ceridwen]

I wish you would reverse dementia

[Steve H]

Have a look at this it might even help with dementia if we are really lucky.

http://www.ncbi.nlm....pubmed/25632141

[alc]

Right a quick update. BioViva is interested in working with Longecity and is going to apply for funding for a pilot study with hTERT delivered to a patient using AAV gene therapy the same one Dr Fossel wants to bring to the FDA. Liz Parrish believes it would be a single patient pilot study for rejuvenation for this level of funding and it would be targeting skin cells on the face to the sub dermal level. Lets hope we can work with them and put this big question to the test, we have the chance for some really disruptive science should we take the dive?

 

I'm interested in donating in any promissing therapy that is done in humans and pets!

 

I'm a bit tired to read tons of studies done in mice, crickets, aliens, etc., to find out after couple years

that is not working in humans + pets.

 

Do not get me wrong, I like mice and I want them to live forever as well, just that first we have to be able to

do that for humans, then our pets and then mice.

 

Also in this day and age, we need to see results, not tons of papers. I think papers were good 10 years ago, but now there

is a lot of evidence and to confirm or not we need studies in humans (or organs-on-chip).

 

I want BioViva to succeed! and set a good precedent.

 

Are they going to post here, or what is the plan?

[Steve H]

Do not get me wrong, I like mice and I want them to live forever as well, just that first we have to be able to

do that for humans, then our pets and then mice.

 

 

  Exactly! I think this cartoon says it all tbh

 

 

 

But more seriously I believe Liz will be sending an application for a fundraiser shortly and I hope might drop by with some details for us soon. All I know for sure is its a limited pilot test with 1-2 people, it will be AAV delivered hTERT gene therapy for the skin most likely the face. I expect the face was chosen as changes would be pretty obvious visually even before biomarkers are measured for changes.

 

If the project is agreed they would then need to build the viral vectors but I think we would learn results fairly quickly given how fast rejuvenation was seen in both human cells tested in-vitro and in the various studies in rodents. Lets hope we can get this rolling and start moving into some really disruptive science. Oh course lets hope it works too.

 

Also she will be talking in Palm Springs at the Brink institute show 5-7 June too in case anyone is going to that show, it sounds like a really good event but it is a little too far for me to walk being in the UK

[zorba990]

Do not get me wrong, I like mice and I want them to live forever as well, just that first we have to be able to
do that for humans, then our pets and then mice.

Exactly! I think this cartoon says it all tbh




But more seriously I believe Liz will be sending an application for a fundraiser shortly and I hope might drop by with some details for us soon. All I know for sure is its a limited pilot test with 1-2 people, it will be AAV delivered hTERT gene therapy for the skin most likely the face. I expect the face was chosen as changes would be pretty obvious visually even before biomarkers are measured for changes.

If the project is agreed they would then need to build the viral vectors but I think we would learn results fairly quickly given how fast rejuvenation was seen in both human cells tested in-vitro and in the various studies in rodents. Lets hope we can get this rolling and start moving into some really disruptive science. Oh course lets hope it works too.

Also she will be talking in Palm Springs at the Brink institute show 5-7 June too in case anyone is going to that show, it sounds like a really good event but it is a little too far for me to walk being in the UK

Please don't do the face. Pick back of the calf or someplace that won't ruin someone's life if something goes wrong. There is alot of excitement and things will change quickly enough if there are positive results...

[YOLF]

I just wanted to post a correction:

 

I think I was discussing this here... One of my information sources was updated. It looks like Heterzygousity (Rs9536314(G;T)) for the klotho gene variant is associated with longer lifespans and increased intelligence. However homozygosity (G:G) does not increase klotho levels and may decrease intelligence (still reviewing).

 

So it looks like therapy for this particular combination will may require testing/application of the therapy with each generation to sustainably reap lifespan and intelligence benefits. The G:G allele is looks like it's rare now, but would become much more common and may carry an impediment.

 

Looks like I've got a bit more reading to do...

[Steve H]

Bioviva is applying for funding with Longecity once Liz is back from Brink at Palm springs for TERT gene therapy according to a conversation I had with her yesterday. It is going to be a localized skin test of the gene therapy and the chosen target is likely to be the hand as that is an area which shows aging and any rejuvenation should be obvious. I believe the patient is in their late 40s and has signs of aging to a level that makes any changes obvious. Fingers crossed the fundraiser is accepted and the project gets to put an age old question to the test.

 

Telomeres I personally don' think cause aging but I agree with Dr Fossel that they are a place to intervene on aging and epigenetically reverse the situation. Dr Fossel is hoping to bring the very same gene therapy to the clinic via the FDA though that is of course the slow road, this pilot study could help pave the way a great deal.

[niner]

Who is Liz?  What does she do?

[Steve H]

Liz is the ceo of bioviva

[Steve H]

Well looks like bioviva has applied to longe city to help with a pilot study. They are at brink at Palm springs this weekend if anyone is going and wants catch them there. Really hoping they do this.

[resveratrol_guy]

Who is Liz?  What does she do?

 

This mind blowing, if a bit hypey, YouTube video will introduce you to Liz Parrish and everything she's hoping to do with BioViva, which is built around everything we might do with an AAV toolkit. Personally, I'd prefer inflated claims that only partially hold up in the end, to FDA approval of nothing at all.

Edited by resveratrol_guy, 08 June 2015 - 09:12 PM.