San Jose Aug 21-23
Herbal Telomerase Activators
As far as I know, Product B is the best commercial telomerase activation product. (For background read this blog entry. All currently available telomerase activators are inadequate, and they may have only nominal effect – we don’t know.) Product B is manufactured by Isagenix, based on cell culture testing at Sierra Sciences. Sierra screened hundreds of herbal products, reporting their results to Isagenix in black-box mode, blind to what they were testing.
I now believe that the lowest-level ingredients in Product B (last on the list) are more potent than the highest-level ingredients (first on the list). For the last nine months, I have been supplementing with the first four herbal ingredients in Product B: Silymarin, Ashwagandha, Horny Goat Weed and Bacopa. I plan to look into the last six ingredients: Boswellia, Maca, Hawthorn, Harada, Shilajit and Chia seed extract. Complete list of ingredients here.
Note that there are no extracts of astragalus in Product B. I have contradictory information about whether cycloastragenol is a telomerase activator.
George Church of Harvard’s Stem Cell Institute led the conference off with a summary of progress in CRISPR technology. I had never heard of CRISPR until last year. As of last year, it was a way to gain more control in genetic engineering. A protein could be engineered to seek out and bind to a specific spot on a specific chromosome, so that the experimenter could now specify where in the gene would be inserted.
Well, that was so last year. Now the protein has been replaced with an RNA sequence that can be specified as an exact complement to the particular region of DNA that is targeted. Easier, and more reliable. And – this is the biggest news of the conference – CRISPR can now be married to a gene promoter or repressor, so that particular genes can be turned on and off using CRISPR. This is possible not just in cells but in living organisms, potentially in you and me.
It is my belief that aging is controlled to a great extent by gene expression. Young gene expression creates a young body. Our bodies know how to be young, if we instruct them to do so. Well, we now have the language to tell the body to be young. We also have a good selection of genes to start with, genes for hormones that we have too little or too much of as we age. What are we waiting for.
A questioner asked George about interaction with “chromatin state”. In any given cell, at any given time, some of the DNA is unwrapped and available for expression, called euchromatin, while the rest, called heterochromatin, is spooled around protein spindles (histones). George indicated that the CRISPR technique works a lot better on euchromatin than on heterochromatin, as we would expect, but that it works some even on heterochromatin, and we’re learning rapidly.
CRISPR is a very new technology, still in the explosive stage of development, and I promise to write a full post about it soon.
Ecological consequences of longevity
Caleb Finch, who wrote the book on genetics of aging more than 20 years ago, still carries an encyclopedic knowledge of research in the field. At RB2014, he placed aging and anti-aging in the context of human imact on the environment and environmental impact on humans. Anti-aging leads to population growth, unless we can couple it with reduced fertility. Population growth leads to habitat loss, species extinctions, and loss of biodiversity. Population density also contributes to pollution, which can accelerate aging. Particulate pollution, associated with diesel engines especially, accelerates amyloid deposits and cognitive decline. Air pollution also exacerbates heart disease. Alzheimer’s Disease has been increasing steadily the last 40 years as heart disease has been in decline.
I learned from Judith Campisi that senescent cells send out signals that potentiate cancer, and from Evan Snyder that stem cells send out signals that promote growth and health of cells nearby. Yea, stem cells! Boo, senescent cells! Only recently, it had been thought that senescent cells were merely slackers, no longer able to perform their function, but it turns out that they emit signals that have a negative systemic effect as well. Only recently, it had been thought that healthy stem cells were able to repair and rebuild damaged tissue, but it turns out that they emit signals that have a positive systemic effect as well. These are global signaling properties that are just coming into focus.
Brock Reeve of Harvard Stem Cell Institute gave us an update on recent work on the signal protein called GDF11 (for Growth Differentiation Factor), which circulates in the blood. We have less GDF11 as we get older. Just this spring, two article came out in Science which demonstrate that GDF11 can stimulate growth of new neurons and muscles. Last year, it had been reported that GDF11 also can reverse damage to aged hearts. It may be impractical to administer GDF11 intravenously as a systemic rejuvenating factor, but the race is on to discover promoter treatments that enhance expression of our native GDF11 gene.
Skepticism from the conference organizer
I found it ironic that Aubrey de Grey, whose SENS Foundation sponsoted the conference, expressed skepticism about this whole approach to aging. He sees aging as a matter of accumulated damage rather than perverse signaling, and he imagines that epigenetic changes that happen with age are actually evolved for the body’s benefit. He distinguished systematic epigenetic shifts with age, which he thinks are beneficial, from random epigenetic drift, which he thinks is detrimental.
Stem cell therapy for heart disease
Linda Marban of Capricor Inc in Los Angeles reported on research to cells from the patient himself, treat them in vitro to turn them into stem cells, grow the stem cells in a petri dish, and then inject them into the patient’s heart, where they can repair damaged tissue. The technology was described several years ago in this Nature article.
Stem cells to treat Parkinson’s Disease
Stephen Minger reported on the potential for applying this same technique to teat Parkinson’s Disease. Foetal stem cells have already been used with some success, though, of course, they tend to be rejected by the patient’s immune system. Using induced pluripotent stem cells (IPS cells) derived fromt the patient’s own cells should solve this problem. It is now known that the brain already contains stem cells, and that in cases of stroke and brain traum, stem cells migrate to the site of the damage and activate to repair the damage. Minger speculates that new nerve cells might be routinely required in order to form new memories.
OVERALL, I had the impression that there are now significant anti-aging technologies poised to move out of the lab and into testing and marketing. Funding issues, marketing, regulation and logistics will impose frustrating delays.
Like a true believer Aubrey will fight to the death, fight the evidence, but if he’s really following my leads he may actually produce a cure for aging – and that’s what he (we) want, isn’t it? So that’s it; signaling leads to aging – and you’ll be surprised (with my next paper) at how that works. You’ll find that Klotho is a signaling molecule which inhibits some aging processes, and so are the Notch proteins, and smads, and now GDF-11, and if you read Irina Conboy’s latest paper, you’ll discover that oxytociin will rejuvenate skeletal muscle. Earlier you may have read Villeda’s news that another signalling molecule, CCL-11 – actually promotes brain aging and accumulates in aging brains – and that another potential signalling molecule – the malformed Lamin A gene called progerin, absent in young people is found in increasing concentration with age – when present in young people it causes the premature aging disease progeria, (Huntington Gilford Progeria). Now it has been found that microRNAs, small polynucleotides that inhibit the synthesis of proteins they target are carried in the blood and that these miRNAs are bioactive – cells’ behavior is changed by them. The search for “the” anti-aging molecule is futile – but the answer (connect the dots yourself) is already published (Katcher 2013). Sadly, I talk and people think just another ‘life extension’ scheme – but it is not.
Exciting, rational, and actionable… If molecular signaling is as important as the heterochronic parabiosis research seems to indicate, we need to support additional study in this direction. I look forward to reading Harold’s next paper and the next entries in this excellent blog.
There is an upcoming trial for Alzheimer using GDF-11.
Probably people know about it, but in case not, here is the
article I saw:
“Young blood to be used in ultimate rejuvenation trial”
@ Harold Katcher – I’ve read your article a while ago. Very interesting. How hard is to put in place a study based on your research and try to fund it via sources like LabCures?
As well like others here, looking forward to your new studies/articles!
On August 25th 2014 Isagenix has release the 4th generation Product B named Product B IsaGenesis. link: http://www.isagenix.com/en-CA/products/categories/individual-items/product-b
It’s say that they have increase the dosage of active ingredient by about 20%
I have also notice that they have remove four component and had five new.
First they replace the DL-alpha lipoic acid by the R-alpha lipoic acid wich seems to be the more efficient, then they remove the Chia, the Hawtorn (root and fruit extract) and the Plantain by a mix of carotene (alpha, beta, lycopene, lutein, zeaxanthine). That’s for the new product B.
What I find strange strange with the product B, a telomerase activator product, is that a least 2 of the ingredient inside ( I don’t check for all) are telomerase inhibitor: – The curcumin : http://www.ncbi.nlm.nih.gov/pubmed/23192708
-The Milk Thistle : http://www.ncbi.nlm.nih.gov/pubmed/15076315
Maybe they are more like telomerase regulator activating telomerase in healthy cells and inhibiting it in cancerous cell than just telomerase activator stricto sensu
Can you explain it to me so that I undestand all this ?
Thank you, Maniere. This is new information for me, and I don’t know how to explain this change in ingredients. I have been relying on a confidential source to recommend Product B and its constituents, but now I think I should back off until I have a public source.
I believe that some substances inhibit telomerase in cancer cells and promote telomerase in normal cells, but I know data on this is weak. Perhaps the Isagenix formulators are thinking that they should include anti-cancer ingredients in Product B in case activating telomerase turns out to promote cancer. I don’t believe that telomerase promotes cancer.
I am confused by the fact that at least three of the ingredients (silymarin, glutathione and curcumin) are known to have very poor bioavailability, and the formulation seems to include nothing that might enhance absorption.
Well, they include as well B12 in the form of cyanocobalamin, which is crap. One has to wonder, which ingredients are for telomerase activation, which ones for preservation of the mix (as the Vitamin E/C they include), and which ones to confound potential copy-pasters like us.
Exciting times, I imagine with SENS vs Signalling both will ultimately play their part as eventually damage which our bodies have no way to clear would prove a problem eventually. But if signalling and telomerase can work keeping people healthy longer and sooner and more affordably I imagine is on the cards. I do admire the amount of joined up thinking that SENS does in funding population studies, talking to legislators and creating dialogue etc, in the UK the state broadcaster is even starting to give him air time albeit late night.
Was there anything more on whether telomerase does promote cancer definitively one way or another? If telomerase does work safely would that mean the injections of stem cells envisioned by SENS wouldn’t be needed? I’m leaning to it not but cancer is a such a scary prospect. Having just read about Product B being best but you backing off, cycloastragenol potentially not being any good is there any products you would currently recommend?
Was there any formal or informal discussion about Calico’s focus or Human Longevity Inc’s for that matter? Reading about CRISPR which I also hadn’t heard of before that was the first thing I thought of.
I do wonder how this what might be going on with those early adopters with a lot of money, eg sports doping as someone must have read about the likes of NAD and GDF11 and saw an opportunity. Not sure it’s even quite doping if it’s more restoring full function rather than gaining a level they would otherwise never achieve.
The Ultimate Rejuvenation trial was front page on New Scientist. It did spark fears of people suddenly thinking billionaires are going to be like vampires in the future with young people being pursued for their blood. Hysteric fears aside, if it gets the results that are expected I imagine the hunt for other growth differentiation factors would be on with new backing and probably put other research in the spot light with increased credibility. Biggest industry on the planet could really start growing here. Which is great as you look at what people in age/health charities are looking at and they seem to very much ignore this whole field as a potential fix for their woes. Most people don’t even know that in one aspect at least they have anything to be jealous of a lobster for. Actually really nervous for this trial!
Sorry, so many questions! Thanks for reporting back, would of loved to be able to be there.
Thank you for alerting me to the Stanford “Ultimate Longevity” trial. You were the first to connect me with this information.
Tony Wyss-Coray at Stanford Med School will begin trials in October, transfusing blood plasma from young donors into Alzheimer’s patients.
Several of us have been speculating that young gene expression can create a young body. We’re about to find out.
More information at New Scientist.
First time posted. Appreciate your blog Josh…
re: Silymarin and Curcumin being Telomerase Inhibitors…
Yes, Silymarin inhibits Telomerase in cancer cells. But take a look at this…
and check the same behavior of Resveratrol (found in Product B IsaGenesis)
Haven’t found a Curcumin Activates Telomerase study…
Thanks for your time and effort about these issues Josh!
Ever since i read about the parabiosis experiment, I’ve been wondering, shouldn’t they limit the age of blood donors? Seems to me I don’t want a transfusion from an old person.
In the latest Time Magazine (Feb 23/Mar 2, 2015, pages 83-86) there is a discussion about longevity and supplements. Dr. Elizabeth Blackburn states, “Cancers love telomerase, and a number of cancers up-regulate it like crazy” followed by “We don’t know how to strike some kind of balance. My feeling would be that if I take anything that would push my telomerase up, I’m playing with fire.” WOW.
Anyone have more info on this? Any testing with Product B in relation to cancer (my experience has been people selling Product B telling me cancer or tumors are not an issue with Product B, and thus no testing for it and no one looking at that potential issue with use).
Could be coincidence, but after four months of use my wife has a growth appear on her chest that was increasing in size and roughness quickly, and after reading the Time Magazine article we stopped using Product B until more facts, but after stopping the growth is now reducing in size (still going to have biopsy this month). For me, at five months use, had a couple mole looking growths close to each other appear and enlarge quickly, then when Product B was stopped they quit growing and have reduced a bit in size.
Wrote to some high up Product B reps and the response i got was Dr. Andrews and Dr. Blackburn have “bad blood” between them, this is politics, this is “bogus science”, and “95% of scientists disagree with what the article says”. Yet no study, no quotes from the disagreeing doctors, and nothing to show the statements from Product B reps are actually true. Then a suggestion to speak with a Dr. Michael Brathman at Pine Street Clinic, a cancer center, because he suggested a patient with cancer use Product B.
Anything from anyone here that can convince me that Product B does not have increased cancer and/or tumors with regular long-term use? Anything to say Dr. Blackburn is incorrect or making these statements due to bad blood with Bill Andrews? Anything?
Yes, there are many scientists in the field who believe that activating telomerase can cause cancer. There are probably more who agree with Blackburn than with Andrews, so that “95%” figure is not right.
However, I am in the school with Andrews. I have written a lot about this subject, and I’m writing more. Reasons for believing that activating telomerase might increase cancer risk are entirely theoretical, as far as I can see. All the experimental evidence is on the other side – that animals treated with telomerase inducers have lower incidence of cancer.
There are two forces at work here in opposite directions:
(Bad) Once a cell becomes cancerous, it can only continue to grow if it has telomerase. So giving the cell telomerase removes one barrier to malignancy.
(Good #1) The body’s primary defense against cancer is the immune system. As we get older, our blood stem cells slow down because their telomeres are too short. Telomerase rejuvenates the immune system, and helps the body fight cancer before it gets started.
(Good #2) When telomeres in a cell get too short, the cell goes into a “senescent” state, in which it spits out hormones (called “cytokines”) that raise inflammation throughout the body and damage cells nearby. Telomerase protects against this.
(Good #3) When telomeres in a cell get too short, the cell’s chromosomes can become fragmented and unstable, and this can lead to cancer. Telomerase protects against this.
I believe that the three “goods” far outweigh the risk from the one “bad”. In animal experiments this seems to be the case, and I think that the “theoretical” reasons for concern are based on bogus theory. However, we won’t know for sure until we have more experience with humans.
Ah, now i’m beginning to understand.
Appears increasing telomerase and presumably telomere length does not as far as we know “cause” cancer, and may even help prevent it.
However, if you already have cancer cells (whether malignant or not), even pre-cancerous cells, it appears adding telomerase feeds it to grow rapidly in some types of cancer and could keep it alive longer.
So the advantages outweigh the risks if you don’t already have some cancer cells in your body. And this is very hard to know since we don’t test for it.
Just wondering if that is a general summary of your understanding too?
I agree I would not take telomerase therapy if I were a cancer patient. But I wouldn’t go so far as to say I’d avoid increasing telomerase just in case there’s cancer already growing somewhere inside me.
So when we are young, we could have pints of our own blood stored in a freezer for when we get old?
I have held off on taking Product B for several reasons, but primarily because the formulation seems to contain a high level of Vitamin A from beta-carotine, Vitamin C, and Vitamin E supplements (see: http://www.isagenix.com/~/media/product/product-b-isagenesis/product-b-fact-panels/us-en-fact-panel-product-b.pdf). My understanding is that recent research indicates that each of these vitamins, when ingested in supplement rather than food form, have an inverse correlation with long term health and longevity. Is my understanding correct? If so, why would Product B contain such added vitamins?
You might be right, Matt. The best evidence in favor of your position is the ATBC study from Finland. But listen also to what Rhonda Patrick has to say. She thinks the detrimental effects only apply to smokers.