For people who have a few hundred thousand dollars to spend and are willing to take on the risks of an “early adopter” and travel to South America, options are now becoming available that were inconceivable just a few years ago. A new company is leapfrogging over the time-consuming process of testing and regulatory approval, and offering the best-established and most promising experimental anti-aging technologies in the near future. This is a new vision for combining research with treatment, for treating diseases that have no proven therapies, and for aging itself.
(This column begins with a couple of pages of background. If you want to cut to the chase, scroll down to BioViva.)
You only have to read Time Magazine to notice that this is the year anti-aging medicine is coming of age. Promising life extension technologies are being debuted, with potential for preventing many diseases at once, adding decades to the human life span, and restoring youthful function to an aging body. These include telomerase therapies, stem cell therapies, epigenetic reprogramming, removal of senescent cells, plasma transfer, and hormonal therapies inspired by gene expression changes between young and old.
Inevitably, this has brought a surge in the number of companies eager to jump the gun and offer treatments to consumers based on early lab research, before the technology has proved safe and effective in humans. In an age of wildcat capitalism, we are well-advised to approach all claims with a skeptical eye, and assume that hucksterism is rampant. Anyone who considers signing on with a new company that is offering a promising but unproven anti-aging technology had best start with a foundation of second opinions and broad considerations of risk and rewards.
But I stop short of saying, “stay away”. The field is too important, with too much at stake for us individually and as a human community, to sit on the sidelines, to wait for the research to be sorted out. Political control of medical research has protected us imperfectly, and has held back life-saving treatments, sometimes for decades. The system serves pharmaceutical profits more effectively than the public of medical consumers. Too often, the treatments that are approved are not those that offer the best risk/reward ratio, but those that are patentable and owned by someone who can afford to invest hundreds of millions of dollars in scientific advocacy.
The standard path to regulatory approval respects individual human life, and is “conservative” in the Hippocratic sense of “first do no harm”. But it is far from the most effective way to move science forward, and probably is not the most efficient way to save the most lives, even in the short run. Many libertarians, anti-aging enthusiasts and ordinary citizens who find themselves with a condition for which there is currently no effective medical treatment want the freedom to participate in experimental medicine, and experimental medicine certainly wants to try to help them and to learn from successes and failures.
For people who see their options for an active and creative life being closed by age-related disabilities, for people who are willing to take personal risks to help move the science forward, for people who are bold and adventure-seeking, the choice to try experimental anti-aging technologies can be a rational decision.
The Promise of Telomerase Therapies
In my opinion, the best-validated and most promising of the experimental therapies is the direct delivery of telomerase through gene therapy. This is a technology pioneered in mice by Maria Blasco’s lab in Madrid, with stunning results. In a ground-breaking 2012 paper by Blasco’s student Bruno Bernardes de Jesus, ordinary lab mice were given gene therapy with an “extra” telomerase gene spread to their cells by a genetically-engineered virus. the mice lived 13-24% longer, and the experimenters reported “remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging.”
Some strategies work better in mice than in humans, but there is theoretical reason to believe that this technique should work (even) better in humans than in mice. Untreated mice already have plenty of telomerase, and the telomeres of lab mice are at least 3 times as long as humans’, with shorter life spans in which to lose their telomeres. Before the above experiment, it was reasonable to think that telomere length was a primary aging clock in humans, but not in mice. Mice can live up to six generations after their telomerase gene has been knocked out (no telomerase at all), whereas people exhaust their telomere endowment in a single generation.
I’ve written in the past about telomere length as one of the body’s primary aging clocks. Very little telomerase is expressed in human adults. As our stem cells divide during a lifetime, telomeres get progressively shorter with age. Some results include the most important symptoms of aging:
- fewer functioning stem cells to replenish the stock of blood and skin cells
- more senescent cell, each sending out distress signals that promote the body’s hyper-inflamed state
- decline of the immune system, as new white blood cells form more slowly
- a cascade effect, as cells with short telomeres senesce and then trigger senescence in neighboring cells
- higher cancer rates, as the chromosomes in cells with short telomeres become unstable, and the immune system sentinels that nip cancer in the bud go AWOL.
Yes—higher cancer rates result when telomeres get short. There is a theory that our bodies withhold telomerase in order to prevent cancer, but it is an idea with no experimental support. Fear of cancer has held back telomerase therapy, and this is a red herring, based on misunderstanding of evolutionary biology. All evidence suggests that telomerase therapies will lower cancer risk.
BioViva is a new company offering experimental medical services outside US borders. Their team includes
- a lab that provides genetically modified viruses with a gene payload, made to order. (This has now become a reliable and predictable technology.)
- A doctor who has experience with experimental gene therapy, and who had the courage to experiment on himself five years ago, with good outcome thus far.
- Sites in Colombia and Mexico where doctors will administer therapies for which there is not yet FDA approval.
- Most important, a Scientific Advisory Board that includes two of the most prominent, senior biochemists who developed the science of telomerase in the 1990s and before. They are Bill Andrews and
Michael Fossel. [This was my error when I wrote up the article. Fossel is not on the advisory board of Bioviva. The board is listed here, and as of 2016Feb, it includes George Church and Bill Andrews].
What they offer is gene therapy with hTERT and a proprietary myostatin inhibitor “in the same family with GDF-11,” according to CEO Elizabeth Parrish.
Parrish stresses that AAV gene therapy is a mature technology and has already passed FDA tests for safety. “AAV has become increasingly common as a vector for use in human clinical trials; as of [2008], 38 protocols have been approved by the Recombinant DNA Advisory Committee and the Food and Drug Administration (FDA).” [ref] The uncertainties are no longer about safety, but about whether the virus will be destroyed by the body’s immune system before their payload can be delivered. The rejuvenation benefit is likely to be systemic, and will have ripple consequences that we can only learn with human subjects.
In a surprise marketing move, Parrish has offered a guarantee for Patient #1 only. If results for the first patient are disappointing, and Bioviva learns to avoid pitfallss and do a better job over the next 2 years, Patient #1 will be re-treated without cost, using the updated technology.
How Gene Therapy Works with AAV
AAV stands for Adeno-Associated Viruses, and there are several types in use. This virus makes its living by
- slipping its payload of DNA into a human cell (shedding its protein shell at the cell wall)
- finding its way to the cell nucleus
- copying itself into a specific place on Chromosome 19,
- from where it manufactures copies of its own DNA, and also of the proteins that it needs to replicate, to penetrate other cells.
In therapeutic applications, the AAV DNA strand is modified to include a payload of therapeutic DNA, and to eliminate the genes coding for proteins that AAV needs in order to reproduce. In this form, the modified virus can infect a cell, but once inside it cannot reproduce, infect more cells, reproduce there, and spread, causing disease. It becomes a one-trick pony. Each individual virus can infect one cell only, and then it has shot its wad. No way this infection can “go viral”.
AAV therapy has been studied for over 25 years, and there is some reason to expect that the payload gene can remain active for a long time. So this is a permanent change in the DNA of some cells in the body, though it is not a permanent infection. Though AAVs are common in the environment, 80% of us have a naive immune response, so the treatment can be effective. (For the other 20%, temporary immune suppression may be necessary.) Repeat treatments are sometimes possible. Here is a good semi-technical introduction to the subject.
Adeno-associated viruses, from the parvovirus family, are small viruses with a genome of single stranded DNA. These viruses can insert genetic material at a specific site on chromosome 19 with near 100% certainty. There are a few disadvantages to using AAV, including the small amount of DNA it can carry (low capacity) and the difficulty in producing it. This type of virus is being used, however, because it is non-pathogenic (most people carry this harmless virus). In contrast to adenoviruses, most people treated with AAV will not build an immune response to remove the virus and the cells that have been successfully treated with it.
Different AAV viruses can be customized to infect different cell types, and of course the place where the virus is injected is the most likely place for the virus to take root. Viruses used in previous generations of gene therapy tended to disrupt the body’s own DNA by inserting at sites that are essential, and cancer rates were raised by some early forms of gene therapy. AAV is favored because its target site seems to be safe, and its insertion harmless.
Therapies with hTERT and Myostatin Inhibitor
hTERT is only half the telomerase molecule, but it is the half that is in short supply, and hence the bottleneck for production of telomerase. Of course, the DNA in our every cell contains the hTERT gene, but it is covered up and remains un-expressed almost all the time. The new copy on Chromosome 19 is active, and in tests in cell cultures and live mice, telomeres have been lengthened.
I believe that telomerase is the closest thing we have at present to a cure for aging. Bill Andrews and others have a long-term goal of developing drugs that will signal the body to activate its own telomerase gene, but these seem to be a few years off. For now, adding an extra gene for hTERT may be the most promising generalized anti-aging intervention. An important issue is that a large viral dose may be needed to saturate the body’s stem cells with the gene payload. This is because a small minority of cells with the shortest telomeres is the source of some of the body’s biggest problems. We’ll learn about the body’s response—if we are lucky, a rejuvenated immune system will itself eliminate the residual senescent cells without the need to lengthen telomeres in every senescent cell.
The myostatin strategy grows from (of all things) body-enhancement strategies for muscle-builders. Myostatin is a member of the TGF-β family, is also called GDF-8*, and is a gene that inhibits muscle growth. So if myostatin can be tied up, there is less inhibition and more muscle growth. In the last several years, creatine has become a popular supplement for body-builders, and it works directly at the level of the gene, by inhibiting expression of myostatin=GDF-8. Later in life, expression of the myostatin gene increases, and it is thought, logically enough, that this is a cause of the loss of muscle mass (sarcopoenia) that is almost universal with aging (though it is mitigated by exercise). Bioviva offers gene therapy for a myostatin inhibitor (the specific gene is not disclosed), and it has been tried by one of the team members, experimenting on himself 5 years ago, with good results in a younger man. Here is an article that offers a balanced view of reasons to believe this might or might not work for age-related sarcopoenia.
Perhaps more important, the same gene has been found to clear blocked arteries, with expected reduction of the risk for heart disease and stroke. There is rodent data and good theoretical reason to expect this will work, and there has been one heart patient who has received the AAV/myostatin treatment it with excellent results. Blocking myostatin is also expected to reduce the progression of insulin resistance that is a driver of many age-related diseases.
Alzheimer’s Disease
There is a well-supported theory of AD that it has its roots in the microglial cells of the brain. These are not nerve cells, but they act as a kind of immune system for the brain, protecting it from inflammation and cleaning up plaques. Their secretions promote growth and repair. Unlike nerve cells, microglia are continually replicating, and so they lose telomere length over time. On the theory that restoring telomeres in the microglia will reverse dementia, Bioviva is offering gene therapy with hTERT in the brain as treatment for AD. Direct evidence that this might work comes from a 2011 experiment from the de Pinho lab at Harvard Med School, in which brains atrophied in mice deprived of telomerase, and the brains actually regrew when telomerase was provided.
The Bottom Line
Experimental treatments are, by definition, at the wrong end of the learning curve. But there is so much to be gained, and the people involved are such experts, that I am deeply hopeful about Bioviva’s work, and the prospect of a fast track to meaningful anti-aging therapies.
____________________
* Myostatin is GDF-8, not to be confused with GDF-11, which has also been recently in the news. Both are in the TGF-ß family. GDF-8 inhibits muscle cell growth, while GDF-11 inhibits nerve cell growth. Curiously, Bioviva’s anti-aging strategy is to suppress GDF-8 but last year’s headline-making paper from Harvard found benefits in promoting GDF-11.
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Thank you for this superb article Josh and I share your optimism for this therapy. Hopefully with demand and improved supply network the costs will fall rapidly once the therapy is proven.
Now the big question for me is, will resetting the Telomeres reset a more youthful Gene expression as well as rejuvenate the cells?
>Will lengthening the telomeres reset a more youthful gene expression as well?
It is clear the will be some change in gene expression from the TPE (telomere position effect). It is also clear that it won’t do the whole job, because gene expression is determined by many epigenetic markers, not just telomere length.
Here’s a challenge for someone to think about: Secretion of blood factors doesn’t come equally from all cells. There are endocrine centers that are responsible for secreting specific hormones, e.g., insulin from the pancreas, melatonin from the pineal. So, where are the glands that secrete most of the body’s GDF-11? Where are the glands that are producing too much NFkB? It is likely that epigenetic reprogramming will be most effective in some parts of the body that send signals to the rest.
TPE-OLD is also surely to be influencing even more distant cells depending on how long the telomeres become with the therapy.
As for the challenge I would guess the Stomach/Intestines secrete a fair amount of factors?
If the glands secreting factors have their Telomeres rejuvenated would that mean in theory they would cease expressing negative factors that age the system too?
Josh… you wrote… “Where are the glands that are producing too much NFkB? It is likely that epigenetic reprogramming will be most effective in some parts of the body that send signals to the rest.”
———
I appreciate the fact you’re scratching for That Specific Answer… The thing is… I’ve already provided you with links to where to find that answer a couple times now in the last 2 months…
Josh… the Life Extension Movement cannot afford to have our best minds, like yours, unfamiliar with this material! So, I’m going to repeat myself and hammer on you as often as is necessary to get your’s and Katcher’s attention…
The organ you’re scratching for information about is the Spleen, a part of the circulatory system so… Yes, it is implicated in the Parabiosis studies… (And, as I mentioned before in an earlier comment, Splenic Macrophages are implicated in the Baati C60 study as well.)
I’ve pasted in 8 graphic figures from key studies that are of interest.
https://drive.google.com/open?id=1LpZvpSRziiCTNJIP-xjy1pQqanLXT6WqCdvgIRJ8gig
I understand that the paragraph below sounds like a marketing pitch… I’m trying to be concise with dense content…
Led by Karolinska Institute Honorary Doctorate Kevin Tracey, dozens of scientists, in at least a hundred studies, with a first milestone study published in 2002, have been Settling the Science of our Innate anti-inflammatory process for Modulating Innate Immunity, the Cholinergic Antiinflammatory Pathway. The CAIP is Triggered by Vagus Nerve Stimulation and/or acetylcholine agonists. It inhibits NF-kB triggered Cytokine Expression Transcription, especially in the Spleen. In humans, whole blood drawn after Vagus Stimulation (i.e., ex-vivo) shows reduced cytokine expression in blood. CAIP Stimulation occurs coincidentally (via acetylcholine expression) with an increase in a measurable statistic, Heart Rate Variability. (That’s why the first 2/8 slides show a spike of Higher HRV in HUMAN elders surviving into their 80s. Conversely, Lower HRV is profoundly correlated with Morbidity and Mortality, as is shown in slide 3.
Slide 8 provides a view of how 1 study, among many, has isolated the Mechanism of Action I’ve described in the paragraph above.
I think the study to begin with to get up to speed is Tracey’s study summary from 2007…
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783813/
Tracey’s latest study summary from 2012 advances knowledge about the Mechanism, including the graphic figure shown in slide 8/8.
Reflex Principles of Immunological Homeostasis
http://www.utdallas.edu/~mxa049000/lessons/research/IL-6%20literature/may%202012/Tracey%20annurev-immunol%202011.pdf
Parabiosis Studies, done without knowledge of the Vagus-CAIP-HRV nexus is a fool’s errand. I first wrote about it in 2012… Wrote you, Josh, that it was implicated in the Parabiosis studies in mid-February…
http://www.longecity.org/forum/topic/56529-the-vagus-nerve-heart-rate-variability-cholinergic-anti-inflammatory-pathway-nexus/
Cheers!
HDW
Dear Wizard –
Thanks for all this material, and I do appreciate your keeping after me. As you can imagine, my stack of things to think about and articles to read is formidable, and I’m always missing things I ought to know about.
May I know your name? If you prefer, you can write to me outside the public forum at [email protected]
– Josh
I am currently trying to help Dr Katcher get a HPE Plasma therapy study funded to prove it rejuvenates like in animals.
Combine that with Telomere restoration and I believe we could be looking at massive increases in lifespan.
Hi Josh… I apologize for a bit of tone in my last note. I get exercised. 🙂
I’m a professional software engineer and my hobby interest and self-education is in Longevity-Rejuvenation research. I’ve posted a good deal at the LongeCity forums. I will contact you via the email address provided with my real name.
My motivation is simple… I’m only several years younger than you and I’m concerned I’ll need a 5 to 25 year short term BioHack to keep me going long enough to participate in an Aging Cure.
I’m hammering on you, Josh, because you appear to have an open mind and understand Evidence is important.
Lucky you!
Steve
Josh Wrote: Here’s a challenge for someone to think about: Secretion of blood factors doesn’t come equally from all cells. There are endocrine centers that are responsible for secreting specific hormones, e.g., insulin from the pancreas, melatonin from the pineal. So, where are the glands that secrete most of the body’s GDF-11? Where are the glands that are producing too much NFkB? It is likely that epigenetic reprogramming will be most effective in some parts of the body that send signals to the rest.
Surely the entire Endocrine system should be the focus of any rejuvenation? Spleen, Thyroid and the master regulator the Hypothalamus in particular worthy of mention.
If exposure to youthful factors restores function in them (and parabiosis hints it might) then the big question is will enough exposure to circulating youth factors reboot the Endocrine system to a younger state eg, Would it change the Methylation pattern to a younger state so it expresses younger genes?
Telemere, Endocrine and blood factor rejuvention tackled at once could perhaps reset the epigentic clock unless I am mistaken?
Rando et al in 2002 showed Liver regenerated within 5 weeks via parabiosis too and that is part of the endocrine system. I see no reason why young blood factors would not do the same for Thymus, Thyroid, Hypothalmus and the rest.
I am wondering if the plasma is somehow reprogramming the Methylation pattern and that is why we see rejuvenation? The possibilities are beyond exciting!
Steve H…
I think you’re right that the plasma can reprogram the methylation pattern such that rejuvenation takes place.
Basic biological knowledge is increasing at an exponential rate and, imho, LE Movement Thought Leaders have not kept up with advances in knowledge of the Vagus-HRV-CAIP-Spleen-Plasma nexus. (CAIP = Cholinergic Anti-Inflammatory Pathway)
That nexus is the most promising place to look to for the mechanism of rejuvenation.
I designed the 8 google slides I’ve posted a link to several times to make that precise point. The first 3 slides show Longevity effects in Humans. Slide 8 suggests a specific Longevity Mechanism. I have enormous respect for Dr. Kacher, but I believe he and others would be thinking about Parabiosis and Transfusions differently if they were familiar with that Mechanism nexus.
I’m a software engineer, not a scientist, but even I can come up with experiment ideas that would be helpful for isolating the Rejuvenation Mechanism vis-a-vis that nexus.
And it’s not that the advance in knowledge of that nexus has taken place especially recently or via some unknown scientist in some obscure journal.
The essentials about that nexus were laid out in 2007 by Kevin Tracey, honorary doctorate holder from the Karolinska Institute. Per ResearchGate, Dr. Tracey has participated in over 400 publications.
Here’s a link to those 8 slides. It takes only 5 to 15 minutes to quickly glance at them. I’m happy to do an online walkthrough of their meaning if asked to do so.
https://drive.google.com/open?id=1LpZvpSRziiCTNJIP-xjy1pQqanLXT6WqCdvgIRJ8gig&authuser=0
Cheers!
HDW
aka, Steve Buss
I said in my last comment that I knew an experiment it would be useful to do… Here’s it is.
Hypothesis: Parabiosis rejuvenation takes place in the older mouse because it has access to a more youthful Vagus-CAIP methylation pattern in the younger mouse’s spleen.
Experiment: 4 Groups of Old/Young mice standard Parabiosis experiment. All 4 groups have the standard parabiosis going on. In addition, the 4 groups are the same groups as shown in that graphic figure on slide 8 of that google slide set I’ve posted a link to.
1 – Control = Standard Parabiosis Only
2 – Cut the efferent Vagus Nerve to the Spleen in the younger mouse along with Parabiosis.
3 – Electrically stimulate the Vagus Nerve in the younger mouse along with Parabiosis.
4 – Use an acetylcholine agonist to trigger the CAIP in the younger mouse along with Parabiosis.
Maybe do some Vagus related things to the older mice too. Dunno…
Look at and understand that slide 8… Given that blood circulates through the Spleen, I don’t understand how something like the experiment I’ve described above an important one to do.
Is it possible for me to join Dr. Katcher’s discussion group. I promise to behave… 🙂
Cheers!
HDW
Dear Wizard –
Is HRV measured by a single Fourier component, as EMWave does it? Or are you talking about a broad-spectrum component, for example the variance of heart beat intervals?
What is the age-adjusted correlation between this measure and all-cause mortality?
Thanks for researching these answers.
– Josh
I believe the plan is to test in Humans not rodents, perhaps Dr Katcher will elaborate on here.
hi i want to be the first african to volunteer to be tested on the medicine. if it work it will save millions of lives, i look forward on hearing from you.
Cool!
There’s this caveat though:
> In an age of wildcat capitalism, we are well-advised to approach all claims with a skeptical eye, and assume that hucksterism is rampant.
We should keep a website (maybe yours Josh? =)) to function as a Market Reputation repository. It’s important for free markets and serves as deterrent for crooks. While I don’t like the FDA, it does serves this purpose for an uninformed public. Now with the internetz we can do much better and avoid conflict of interest to get in the way of solutions.
It also helps gathering data for seeing what works or not, specially the synergies (good and bad) we are expecting to see emerge. I believe the Longecity crowd will probably take this role tho.
> saturate the body’s stem cells with the gene payload.
what happens when more than 1 virus try to insert the payload in the same cell? it just keeps lengthening the chromosome? Kinda crowded already to cram even more stuff =) there are organisms with much more genes, so it can probably take quite a bit yet before bursting, lol.
One last question: we have much more somatic than stem cells, the targeting customization mentioned is enough I trust?
Your question about how to get exactly one virus into every cell is crucial, and I don’t think that medical science yet has a strategy for this. The crude and simple way to address the question experimentally is just to try different dosages of the virus, and I don’t think even that has been done.
Any indication if the therapy targets multiple cell types for body wide therapy or is it selective at this point?
Maybe for us who can afford to wait some more years, time will bring impovements of the therapies and lower costs if everything will work. Humans live longer than rats and time is essential for following how the
‘pacients” respond to therapies after longer periods. Also, for us who can t afford such costs even if we sell everything we have, we can think of the wealthy ppl buying such therapies as guinny pigs 😀
I don’t know for others, but I find this article most provocative and intriguing on this website in last 12 months.
The whole story looks very interesting.
I am just not sure how to think about some people involved…(don’t want to talk about names)
I find this very interesting but until more is known and we have research papers confirming the procdure works safely in Humans it’s a waiting game. I have no doubt as to the ability of the people involved but it is a question of IF anyone is willing to be patient #1 and IF it works as we hope.
Sadly the industry is rife with hucksters, pill pedlars and charletans and the instinct most will have is skepticism until proven otherwise. There is good research out there of course but it is diluted by myriad amounts of quackery.
If they can demonstrate in a person that aging can be reversed it would blow the field wide open, but its all theory until tested and research papers are done.
Agreed.
When I said I find it interesting I meant to say that the fact we are talking about this is interesting. I find subject of this article more daring and, I dare to say, controversial…
It’s going to be a long time before I decide what to think about all this and I will wait for people who know much more than me on this to help me reach my opinion…
I think it has potential as a really powerful rejuvenation technique. It is outside of the US but the experiment could tell us a great deal about aging in a very short space of time if people go for the therapy. The FDA is holding back progress at this moment in time IMO and whilst safety should always be a concern there is a need to be bold and forge ahead too.
Gene therapy has great potential unlike much of the quackery certain groups peddle so I hope the testing does go ahead and once and for all settles the argument over Telomeres. I agree with Josh that rejuvenating them would go a long way towards rejuvenation and very likely would increase lifespan.
I can see the US losing out on gene therapy and much of it moving abroad to places like SA where such techniques have freedom to be tried. It is cutting edge stuff but it could blow the field wide open.
Hi, interesting article.
I did some research, and couldn’t find anything about these treatments by BioViva on the internet. What’s your source for this information? Are you affiliated with them in anyway?
Thanks and Best.
I know Bill Andrews, Michael Fossel, and Liz Parrish professionally, but curiously I heard of Bioviva first through a reader of this blog, and only afterward contacted each of them to learn more about the new company. I have no financial ties to this or any other enterprise.
As far as I can understand they use PRCN-829 as a delivery method which appears to be a patent of Dr Jason Williams of Neuralgene who is also listed as part of the Bioviva team.
PRCN-323 is another one he has developed though again I struggled to find much about testing as that too appears to be a very new therapy. Seems he tests therapeis in Columbia ahead of FDA approval which seems consistent with this article.
I see Bioviva has signed a deal with Stevia First this week to collaborate seeking diabetes and obesity therapy pathways. They certainly seem ambitious.
http://finance.yahoo.com/news/stevia-first-corp-announces-scientific-130000621.html
How can Bioviva offer “Patient #1 will be re-treated without cost, using the updated technology” when the patient will have developed neutralizing antibodies to the AAV capsid?
This is sometimes an issue, but it can be overcome with different strains of AAV and with immune suppressants.
I wonder if frequent injections with PEG-HCC’s would be a feasible way to slow down aging? There has also been rumors of SkQ1, MitoQ, [60]LipoFullerenes etc. Nice to see so many options are becoming available. Ultrasound treatment for the brain every now and then. A treatment with Quercetin and Sprycel. Background antioxidant therapy with next-gen antioxidants. Using the options listed by Josh in conjunction with the options I’ve mentioned.
http://news.rice.edu/2015/02/09/nano-antioxidants-prove-their-potential-2/
http://www.science20.com/science_20/is_tumor_metastasis_prevention_on_the_horizon-142136
http://www.sciencedirect.com/science/article/pii/S0142961212003237
this kind of advanced experimental therapeutic should be debated by leaders in the field of clinical antiaging medicine at the AMERICAN ACADEMY OF ANTIAGING MEDICINE …. http://WWW.WORLDHEALTH.NET all potential issues of risk need to be reviewed and brought to light and if the technology seems to be of great promise with greater benefit than risk…….. that is when is should be offered to potential patients. a4m has over 26000 physician and scientific members from 120 countries worldwide and their endorsement will give great comfort to potential patients. best wishes for the safe and successful outcome to this research project……
dr ron klatz president and founder a4m boca raton florida . .
I am a bit confused. According to the linked short intro
http://www.genetherapynet.com/viral-vector/adeno-associated-viruses.html
in applied gene therapy the Rep sequences are taken out from the virus. This it cannot integrate into chromosome 19 as described here
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929125/
An interesting feature of wild-type AAV is that the genome can integrate in a site-specific manner in a region on the long arm of chromosome 19 (19q13-qter), termed the AAVS1 site [1,8,9]. Although large regions of homology do not exist between the AAVS1 site and the AAV genome, AAVS1 contains an active Rep binding element and the AAV Rep protein (a DNA helicase) is required for site-specific integration of the vector. Thus, Rep-mediated replication at AAVS1 may promote DNA repair processes that allow the proviruses to integrate [10].
!!!
Approximately 0.1% of infecting wild-type AAV genomes integrate at AAVS1 [1]
!!!
More interesting stuff
Synthetic AAV vectors have also been designed to integrate at the AAVS1 site by the same Rep-dependent mechanism. However, the rep gene is toxic and its inclusion in the vector significantly reduces the viral packaging capacity. Progress with rep-containing vectors will not be discussed. The wild-type AAV genome can also integrate at sites in the genome other than AAVS1, as demonstrated by the identification of a provirus on chromosome 1q31.1 in human tonsillar tissue and in multiple different chromosomes in vitro [3,12]. These events were presumably Rep-independent and are analogous to the integration of rep-deficient vectors described in this review.
So even without it can integrate randomly into the genome?
Although the rep independent integration must be orders of less probable than the rep dependent which is also quite poor.
Thanks for finding this Gabor. It seems that I’m the one who is confused. I have heard contradictory accounts of whether the viral DNA integrates. But I have heard consistent reports that the DNA is active for years after treatment. Now I am motivated to go back and learn more.
Josh, regeneration may be much simpler than previously imagined only 2 genes silenced to restore stem cell numbers and activity with no increase in cancer.
Granted only in mouse mammary tissue in this experiment, but i’m sure you can see the potential for a whole body treatment.
http://www.sciencedaily.com/releases/2015/04/150408124628.htm
Yes I saw this study and it is very interesting indeed. I did roll my eyes when I saw yet again the media say its the fountain of youth yet again. No wonder the legitimate age researchers get lumped in with the foil hat hearing conspiracy nuts with media hype like this.
It is however very interesting and means that Parabiosis and HPE rejuvenation should not increase cancer risk when calling up aging stem cells back into service again. This has been a fear and reason for not experimenting in people and this paper here is fairly promising in respect of dispelling that.
Josh – do you think what Bioviva is doing, is it in the right track with rejuvenation/reverse aging process that we are so interested in? I mean, we’ll be also seeing “reverse some aspects of aging” by using their therapies, besides treating/curing what is listed on their web site.
Also, since you know personally some team members, when you have news that can be shared, would be nice if you can update your original post with progress on this. Thanks.
Of course I think what Bioviva is doing is promising, or I wouldn’t have devoted so much space to it. It’s bold, it’s risky, and it just might work. I will continue to report in the space whatever I hear about their trials.
Josh – Thanks for your reply!
1. Besides the benefits they list on their web site, can you say what other parts of human organism you think will also benefit from these therapies? Like visible areas: hair, skin, muscles, etc. – or invisible: like other organs: kidney, lungs, etc.
2. Do you know if any of the team members have tried the therapy on themselves? Would be interesting to ask if they did and if we can have some parameters measured. Would be quite convincing if any of the team members tried that first and show the results – some sort of before and after, but with data attached, as we’ve seen lots of “before and after” but with the power of photo editing tools, you can regenerate whatever image you want. Thanks.
As for rejuvenating muscle, that is easy. No need for gene therapy. 5 grams of creatine per day plus once a week heavy weight lifting. Did I
say easy? No, it is heavy lifting; but age does not matter. Start light and work your way up. This has been proven over the last 50 to 100 years. Plus heavy exercise promotes stronger bones, lungs, heart, and boosts telemerase, too! (Popular lore says it weakens the mind, though (just joking). Disclaimer: I don’t sell exercise equipment.
I am informed they are running a test with htert this year on localized skin cells. They are currently raising funds to do so and results should be fairly quick.
Liz recently gave a talk about their plans here
http://m.youtube.com/watch?v=87OUb8TBwX0&feature=youtu.be
They are certainly ambitious and I really hope this pans out for all our sakes.
I watched most of the presentation. At the beginning she is answering a similar question, and the answer is something like “yes these therapies will make people younger”. Also, she is mentioning that one person is already treated and we’ll see the results in a year from now. Let’s hope for the best. Now things are getting serious in this area and we’ll have measurable results. That is what we want: therapies that can show actually reverse aging, as a lot of promises were made by lots of people in recent years. Definitely we should keep an eye on BioViva. Again, let’s hope for the best.
Anybody knows how much these therapies costs?
Something in the order of around 200k I beleive was the ballpark for a two gene therapy, so very costly indeed. It would require them to build their own manufacturing plant to bring the cost down to a level accessible to more people. Lets hope true rejuvenation does not remain in the remit of the rich.
Dr Jason Williams has apparently taken the Myostatin Inhibitor according to the talk and I have suggested he take an IMT ultrasound to prove the reduction of artery plaque.
They are apparently trying to fund a two gene therapy study this year along with a bunch of other tests this summer. This may be the proof of rejuvenation she is talking about showing in a years time to the people there.
Apparently the Myostatin inhibitor is the same as this one currently in clinical trials for MD at the Nationwide Childrens Hospital and there are initial study results:
http://www.ncbi.nlm.nih.gov/pubmed/25322757
Improvement of muscles, improvement to the 6mtr walking test in some cases very large improvements and it also shows Anti-fibrotic effects in various organs too.
If we have to ask, we can’t afford it. 😉
I think we need to wait and monitor the progress of BioViva, some researches suggests that genetic materials replication is not the only cause of telomere shortening, that cellular oxidative stress also causes shortening, in fact, this research gives the shortening due to replication a very low percentage. http://journal.frontiersin.org/article/10.3389/fgene.2015.00082/full So I guess BioViva experiments will help further our understanding, it might even refute the argument that ‘replicative senescence is not clocked.’
I don’t know that we’ll learn anything as theoretically definitive as that, but we will find out if one path towaard de-aging is likely to be fruitful.
That’s the point, whatever the outcome, we will learn something.
— I believe that the functionality of the Vagus-HRV-CAIP-Spleen nexus is the Best Explanation of Heterochronic Parabiotic Rejuvenation…
— I believe the evidence supporting this belief has has been sitting around in the literature for a while, and I just found a bit of it…
— I believe there is a set of obvious specific experiments that could be relatively easily performed to try to Falsify a properly formed Hypothesis around that belief…
I provide study references, quotations, and graphic figures that take a stab at sketching the scientific study basis for that beliefs in a post today at LongeCity…
http://www.longecity.org/forum/topic/56529-the-vagus-nerve-heart-rate-variability-cholinergic-anti-inflammatory-pathway-nexus/?view=findpost&p=723987
Cheers!
HDW
The rejuvenation seen is likely due to aged Stem cells returning to work after the blood factors signal them to resume function. Factoral signals are very likely epigenetically restoring a younger phenotype in the cell niche and local environment which then leads to the Stem cells resuming production. I also believe signals may in some way increase Telomere length as part of a return to younger gene expression though no one has measured this suprisingly. This would also explain somewhat why Telomerase therapy rejuvenates tissues too.
BioViva are in H+ again with an update on their AAV therapies, they are also at BRINK next month.
http://hplusmagazine.com/2015/05/06/bioviva-gene-therapy-to-treat-aging-and-beyond/#.VUrYltAuDOk.facebook
Bioviva has applied to Longecity for a fund raiser and will also be hosting a main fund raiser via Lifespan.io a new life extension crowdfunding website devoted to life extension science launching in August.
Josh,
Would you think using Creatine to inhibit Myostatin would have some beneficial effects? Ok it isn’t going to be anywhere near as effective as using Follistatin gene therapy to boost cellular regeneration but there is anecdotal data suggesting it might work to a certain extent possibly even boosting cardio vascular health.
Steve – Thanks for the info on HRV. I am new to the conversation, but now I am working on my HRV.
I am a 61 year-old male and my BMI hovers 20. I am concerned about sarcopenia in my old age. Creatine has been shown to help and so does Vitamin D. I get my vitamin d from sunshine during the summer. See the 17 abstracts on Vitamin D and myostatin at
http://www.ncbi.nlm.nih.gov/pubmed/?term=Myostatin+vitamin+d
Also, take a quick look at article at:
http://suppversity.blogspot.com/2013/12/vitamin-d-builds-muscle-70-reduction-in.html
Very interested in anti- ageing therapy such as stem cell therapy. I’m 79 but look in my 60s but I’ve lost strength and speed. I’m looking to regain energy to be able to exercise for longer periods.
I realize I cannot be 30 again but if there is a therapy that will bring back some speed l have lost through the years, I would be interested.
I think you might be interested in my post tomorrow. But don’t raise expectations too high – the technology for what you want may be coming soon, but it’s not here yet.
Hi Josh,
What do you think about Liz Parrish being patient zero ? Do you have any news to share on this?
Thanks
You know more about this than I do. Has she made an announcement? Can you send a link?
http://www.technologyreview.com/news/542371/a-tale-of-do-it-yourself-gene-therapy/
Quote from the article:
Fossell, the anti-aging entrepreneur, says even if Parrish were to somehow succeed in slowing the aging of her body, an outcome he rated as unlikely, the experiment would have no impact because of how it was carried out. “The problem is that no one is going to believe them,” he says. “The credibility will be zero even if they are right on the money.”
I agree with Mike Fossel. Liz has done the right thing in the wrong way. She is too young to be an ideal candidate to see dramatic benefit, and the lack of documentation for the procedure will be a real problem in validating and replicating her result.
Here you go: https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_name_is_liz_parrish_ceo_of_bioviva_the/
Any updates on Bioviva based on Liz’s Reddit interview:
http://www.hairlosscure2020.com/liz-parrish-just-announced-that-she-is-the-first-patient-to-be-treated-with-gene-therapy-to-reverse-aging/
HighDesertWizard – Thank you for the link to article at Technology Review. It provides other hints to the puzzle.
A patent application that Jason Williams assigned to Bioviva relates to ALS. He may have assigned others. Here is a link to the patent application that is known to be assigned to Bioviva.
https://docs.google.com/viewer?url=patentimages.storage.googleapis.com/pdfs/US20140234275.pdf
Michael Fossel has a patent application (note – the article misspelled his last name) directed at getting telomerase into the cells. He uses a liposome.
https://www.google.com/patents/WO2015100269A2?cl=en&dq=WO+2015100269+A2
Hi,
I had recorded a 2 hours interview with Michael Fossel for my TV programe.
He is talking about the most recent ideas regarding reverse aging
Cristian – is that interview available online? Thanks.
I disagree Liz is too young to be patient zero. 45 is too young? It is easier to prevent then to reverse. If she were 35 then it would take too long to see if it worked. If she were 65 it would be an uphill battle to rejuvenate. 45 is about right.
BioViva Plans an Age Reversal Clinic in Fiji as Medical Tourism Gets Weird
https://www.inverse.com/article/15895-bioviva-plans-an-age-reversal-clinic-in-fiji-as-medical-tourism-gets-weird
I’m willing to be a Guinea pig if there’s a possibility of success. I’m only 33 so if stopping it’s easier than reversing it im in.