Nugenics "Elixir"
VP. 18 May 2020
If "plasma fraction" is inadequate to describe the work on Elixir, would here reside the main difference with previous work e.g. by Wyss-Coray team at Alkahest? Just wonder.
I know they found "significant" results with just a herbal formula years ago. It's possible Alkahest has found many of the same constituents as Harold but they are going the slow single disease FDA route.
Thank you Patricio. Yes 45 would be too young for proposed trial. We would like to see significant reversal. But let us see what protocol is designed by Harold. We have had 3 major trials: First one on 10 natural extracts. Each one selected to upregulate a key known repair system whose efficiency goes down with aging. We have had very encouraging results with that but it wont quantify as systemic compared with Elixir. We followed this with 2 trials of Elixir: single dose 30 days and repeat dose 155 days. You have the result of that. Although I cant disclose about ElixirI will say this: Harold came up with brilliant work due to which hopefully we wont have scaling issues and prices will remain reasonable.https://joshmitteldo...rough/#comments
Edited by VP., 18 May 2020 - 04:08 PM.
VP. 18 May 2020
Other companies are searching the same area. https://www.theguard...nts-mice-plasma
I have no idea how Harold leapfrogged such well funded labs.
p75213 18 May 2020
https://mobile.twitt...912928695857152
Mind 18 May 2020
The formula is not being released yet. That does not automatically mean it is a scam. If they are trying to build a company and a fortune based upon this formulation, then they need to keep it secret at this point.
VP. 19 May 2020
Prof Katcher is doing an AMA on Reddit: https://www.reddit.c...th_rats_plasma/
Harold has decided to do the AMA after publication of the study.
albedo 21 May 2020
Dr. Oliver Medvedik will discuss the study in the LEAF Journal Club on May 21st, 1:00 PM EDT, live on Facebook.
albedo 23 May 2020
I think informative from Akshai:
"...we have three products developed: natural extracts mix, young plasma fractions: Elixir and powerful anti aging molecule: gel and transdermal patch. We have completed pre-clinical trials in all three..."
albedo 25 May 2020
Dr. Oliver Medvedik will discuss the study in the LEAF Journal Club on May 21st, 1:00 PM EDT, live on Facebook.
Recorded session:
https://www.lifespan...ic-age-in-rats/
albedo 26 May 2020
Recorded session:
In case you missed, there were quite harsh comments by Didier Coeurnelle, mainly wrt the lifespan study which I understand is in progress.
While waiting for that, here is a potentially contradictory study posted on Josh's blog and Harold Katcher's reply:
"...in addition, this is still somehow in contradiction with
https://onlinelibrar...111/acel.12897"
"...Yes, that’s a question that has been bothering me since Amy Wagers post-doc, Shane Mayack and her papers were retracted from Nature and Blood. What Shane, who said she was innocent of everything, but made a mistake on which illustrations she used (one used previously), showed(she said) that blood cells weren’t affected by the rejuvenating factors in the blood (heterochronic parabiosis) but instead were rejuvenated (after a time) by bone marrow stromal cells. So, that was always a worry of mine – but the rats showed no ill effects at any time, I really don’t know about how good their immune systems were as we never challenged them, what I do know is that the chronic inflammation due to aging (present in all terrestrial vertebrates) disappeared. So, if nothing else, I can definitively say that chronic inflammation due to aging can be reversed with factors present in young blood. Hey, it’s a beginning and with great potential to end the diseases of aging, many of which have an inflammatory component..." (Harold Katcher)
https://joshmitteldo...rough/#comments
rodentman 26 May 2020
In case you missed, there were quite harsh comments by Didier Coeurnelle, mainly wrt the lifespan study which I understand is in progress.
While waiting for that, here is a potentially contradictory study posted on Josh's blog and Harold Katcher's reply:
"...in addition, this is still somehow in contradiction with
https://onlinelibrar...111/acel.12897"
"...Yes, that’s a question that has been bothering me since Amy Wagers post-doc, Shane Mayack and her papers were retracted from Nature and Blood. What Shane, who said she was innocent of everything, but made a mistake on which illustrations she used (one used previously), showed(she said) that blood cells weren’t affected by the rejuvenating factors in the blood (heterochronic parabiosis) but instead were rejuvenated (after a time) by bone marrow stromal cells. So, that was always a worry of mine – but the rats showed no ill effects at any time, I really don’t know about how good their immune systems were as we never challenged them, what I do know is that the chronic inflammation due to aging (present in all terrestrial vertebrates) disappeared. So, if nothing else, I can definitively say that chronic inflammation due to aging can be reversed with factors present in young blood. Hey, it’s a beginning and with great potential to end the diseases of aging, many of which have an inflammatory component..." (Harold Katcher)
https://joshmitteldo...rough/#comments
Thanks for keeping us updated on all this.
I don't understand why there are some who dismiss the entire study due to the fact that there wasn't a life-span study; especially in light of the lock-down. Obviously a life-span study will be included, just as a full peer-review of everything will be on the horizon. And it's extremely hard to believe that S. Horvath would co-author a scam, or a very poorly setup experiment, that consistently came up with inaccurate data.
p75213 26 May 2020
albedo 01 Jun 2020
This presentation by Steven Braithwaite, CSO of Alkahest, seems to me hinting to a serious competitive approach (which is great!) maybe for some of the end-points:
albedo 02 Jun 2020
This presentation by Steven Braithwaite, CSO of Alkahest, seems to me hinting to a serious competitive approach (which is great!) maybe for some of the end-points:
... quite acknowledged by Akshay in Josh's blog:
"Thank you Josh. We are quite excited by the potential potency and economy of our therapeutic for reversal of aging but Alkahest is run by really smart people, they have already raised $50 million and have quietly made multiple products reach Phase II with FDA. They are doing all the right things for commercializing their technologies. Their focus seems to be on individual diseases of aging especially neurodegenerative diseases rather than aging itself which may be driven by FDA. I admire how well they seem to have progressed."
Engadin 08 Jun 2020
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S O U R C E : Josh Mitteldorf's "Aging Matters" blog
- They measured nerve growth factors in the brain, and detected a more robust response, typical of young mice
- They lacerated muscles and showed repair rates typical of much younger animals
- They examined microscope slides of liver tissue, and showed that it is less fatty and striated than is typical of older mice
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Figure 2. Rejuvenation of adult myogenesis, and albumin-independent effects of TPE. One day after the NBE, muscle was injured at two sites per TA by cardiotoxin; 5 days later muscle was isolated and cryosectioned at 10 µm. (A) Representative H&E and eMyHC IF images of the injury site. Scale bar = 50 µm. (B) Regenerative index: the number of centrally nucleated myofibers per total nuclei. OO vs.ONBE p = 0.000001, YY vs ONBE non-significant p = 0.4014; Fibrotic index: white devoid of myofibers areas. OO vs ONBE p = 0.000048, YY vs YNBE non-significant p = 0.1712. Minimal Feret diameter of eMyHC+ myofibers is normalized to the mean of YY [9]. OO vs. ONBE p=3.04346E-05, YY vs. YNBE p=0.009. Data-points are TA injury sites of 4-5 YNBE and 5 ONBE animals. Young and Old levels (detailed in Supplementary Figure 1) are dashed lines. Representative images for YY versus YNBE cohorts are shown in Supplementary Figure 6. © Automated microscopy quantification of HSA dose response, as fold difference in BrdU+ cells from OPTI-MEM alone (0 HSA). There was no enhancement of myogenic proliferation at 1-16% HSA. N=6. (D) Meta-Express quantification of BrdU+ cells by automated high throughput microscopy for myoblasts cultured with 4% PreTPE versus PostTPE serum and (E) for these cells cultured with 4% of each: PreTPE serum + HSA or PostTPE serum + HSA. Significant increase in BrdU positive cells is detected in every subject 1, 2, 3, and 4 for TPE-treated serum (p=0.011, <0.0001, <0.0001, 0.0039, respectively), as well as for TPE-treated serum when 4%HSA is present (p<0.0001, <0.0001, <0.0001, =0.009 respectively). N=6. (F) Scatter plot with Means and SEM of all Pre-TPE, Post-TPE, +/- HSA cohorts shows significant improvement in proliferation in Pre TPE as compared to and Post TPE cohorts (p*=0.033), as well as Pre+HSA and Post+HSA cohorts (p*=0.0116). In contrast, no significant change was observed when comparing Pre with Pre+HSA (p=0.744) or Post with Post+HSA (p=0.9733). N=4 subjects X 6 independent assays for each, at each condition. (G) Representative BrdU IF and Hoechst staining in sub-regions of one of the 9 sites that were captured by the automated microscopy. Blood serum from old individuals diminished myogenic cell proliferation with very few BrdU+ cells being visible (illustrated by one positive cell in Pre-TPE and arrowhead pointing to the corresponding nucleus); TPE abrogated this inhibition but HSA did not have a discernable effect.
What’s missing? They did not test any measures of physical or cognitive performance at the level of the organism.
- Evidence of behavioral changes (learning and memory, endurance, strength)
- Inflammatory markers
- Blood lipids
- Methylation clock (Horvath, UCLA) or proteomic clock (Lehallier, Stanford)
Harkijn 10 Jun 2020
Yes, it is important to go to Josh' site. Not just for the article but also for the fascinating discussions by a number of knowledgeable scientists! One of the contributors is once again dr. Harold Katcher.
rodentman 14 Jun 2020
Man, I just love Josh, and the way he breaks things down, and compares Katcher and Conboy's work. Very fascinating stuff.
Engadin 14 Jun 2020
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Dr. Harold Katcher has been a pioneer in the field of cancer research, in the development of modern aspects of gene hunting and sequencing. He carries expertise in bioinformatics, chronobiology, and biotechnology and is currently working in the capacity of Chief Technical Officer at Nugenics Research Pvt Ltd. exploring in anti-aging modalities.
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rodentman 14 Jun 2020
Thanks. Interesting video. Boy, he sounds very convinced that this is a complete cure for aging.
He says that after rat trials, he will do dog trials, based on the ease of getting revenue from pet-lovers... and after that, human trials. He's trying to rush it as much as possible, but this will probably be at least a couple years from now.
He also said treatment on rats 'peaked' at about 1 month.... and continued for 3 months to be at that YOUNG stage, and then he redid the treatment, with the same result. I am not exactly sure if this means that after 3 months, the benefit 'wore-off', and the rats' biological age returned to the chronological age... or that after the 3 months... the rats started aging at a regular rate, but at the younger age.
QuestforLife 15 Jun 2020
Thanks. Interesting video. Boy, he sounds very convinced that this is a complete cure for aging.
He says that after rat trials, he will do dog trials, based on the ease of getting revenue from pet-lovers... and after that, human trials. He's trying to rush it as much as possible, but this will probably be at least a couple years from now.
He also said treatment on rats 'peaked' at about 1 month.... and continued for 3 months to be at that YOUNG stage, and then he redid the treatment, with the same result. I am not exactly sure if this means that after 3 months, the benefit 'wore-off', and the rats' biological age returned to the chronological age... or that after the 3 months... the rats started aging at a regular rate, but at the younger age.
Its all shown in the paper. Biomarker values improved rapidly to young or near young levels and then declined slowly. For example IL-6 declined from old to young levels in about a week and declined about half way back to old levels in about 3 months. A repeat of the protocol once again restored the biomarkers to young levels (was actually slightly better second time). I am assuming a repeat protocol for humans would be years apart. But we need more data (and lifespan studies) before we'll know for sure.
Mind 15 Jun 2020
It is a great result, but of course, the return to older biomarker levels (to some degree), would say to me that this treatment might not be getting to the root cause of aging (damage) exactly. There is still the question of getting rid of glucosepane, lipofuscin, A-beta, and other garbage. Changing peptide and hormone levels does not get rid of this "junk" as far as I am aware. HGH, other hormones, and peptides, have been used for decades and they improve certain biological functions, but none have truly rejuvenated anyone.
Engadin 15 Jun 2020
Changing peptide and hormone levels does not get rid of this "junk" as far as I am aware. HGH, other hormones, and peptides, have been used for decades and they improve certain biological functions, but none have truly rejuvenated anyone.
Akshay answers, though vaguely to some extent and basing it on deep level auto/mitophagy, the 'debris question' here:
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rodentman 15 Jun 2020
It is a great result, but of course, the return to older biomarker levels (to some degree), would say to me that this treatment might not be getting to the root cause of aging (damage) exactly. There is still the question of getting rid of glucosepane, lipofuscin, A-beta, and other garbage. Changing peptide and hormone levels does not get rid of this "junk" as far as I am aware. HGH, other hormones, and peptides, have been used for decades and they improve certain biological functions, but none have truly rejuvenated anyone.
Engadin 16 Jun 2020
Here is a thread into the paper via the Nrf2 path. Encouraging for those (I do for what it matters) trying to increase intake of sulforaphane:
Here a pretty easy to follow procedure to increase sulphorafane's bioavailability in broccoli sprouts by 3,5 times:
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Harkijn 16 Jun 2020
Thanks for this Engadin! Readers who have joined Longecity in the last few years may not know that there are several SFN threads full of background and tips. This is one of them:
Mind 16 Jun 2020
Akshay answers, though vaguely to some extent and basing it on deep level auto/mitophagy, the 'debris question' here:
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Thanks for sharing this. Akshay seems to be saying that autophagy can get rid of metabolic waste (stuff that is thought to be indigestible/unbreakable), just that the process of autophagy "ages" just like everything else in the body. I am not sold on this. I would be more sold on a theory that resetting an "aging clock" would upregulate beneficial apoptosis. Basically....cells that are burdened with too much indigestible junk or virtually unbreakable crosslinks would be ejected from the body, only leaving the healthy/better-functioning cells behind.
p75213 17 Jun 2020
In the same way that glucoraphanin + myrosinase enzyme = sulforaphane. Glucomoringin + myrosinase enzyme = moringin.
Glucosinolate + myrosinase enzyme = isothiocyanate.
Edited by p75213, 17 June 2020 - 08:44 AM.
Avatar of Horus 20 Jun 2020
An update on this here:
Reversing age: dual species measurement of epigenetic age with a single clock
Raphy 25 Jun 2020
But so far epigenetic reset looked to be very hard. But if this plasma fraction is easy to produce, this will be tremendous.
kurt9 25 Jun 2020
I believe this will prove a major breakthrough, as Josh does. Ever since the first studies showing epigenetic reset reverses multiple hallmarks of aging, the SENS model didn't make sense.
But so far epigenetic reset looked to be very hard. But if this plasma fraction is easy to produce, this will be tremendous.
Aubrey de Grey is involved with AgeX, founded by Michael West, which is working on invivo cellular reprogramming. This is tacit recognition that epigenetic reprogramming is the way to go here.
albedo 26 Jun 2020
Well agreed Kurt9.
Also, the publication is still on BioRxiv but peer-review processes normally take time mostly when claims are important.