231 replies to this topic

[albedo]

Sorry if you have see this paper (2014) on GHK before but it just pop up in Josh's blog and though to put here too:

 

Pickart L, Vasquez-Soltero JM, Margolina A. Ghk and dna: resetting the human genome to health. BioMed Research International. 2014;2014:e151479.

https://www.hindawi....ri/2014/151479/

 

[RWhigham]

Pickart (the guru of GHK) does not look younger than his age to me, so I don't expect visible rejuvenation from GHK.

Edited by RWhigham, 29 November 2021 - 10:19 PM.

[rodentman]

Update on E5.   

Rats are 32 Months Old, 4rth dose has been administered. 

E5 Rats Alive: 8

E5 Rats Dead: 0

Control Rats Alive: 6

Control Rats Dead: 2

 

I'm actually impressed with the control rats.. only 2 dead of old age at 32 months for this species is impressive.  I guess this is just a healthy lot.  I would assume December will bring a lot of rat deaths here.

 

I've attached an image

 

 

 

Attached Files

•  e5-graph-12-7-21.jpg   52.28KB   2 downloads

[rodentman]

Yuvan provided their update on the E5 lifespan study today.

 

 

 

Updates about Yuvan Research

 

After the 4th dose of E5, data and pictures show rats still rejuvenated

 

2 of the 8 control rats already died, and the 8 treated rats are still alive in the Lifespan Study

 

Yuvan Research's Lifespan Study with rats has reached its 10th month, and after 4 doses of E5, the treated rats continue to show the rejuvenating effects of the treatment, according to data collected and pictures of the animals. To date, all 8 treated rats are alive, while in the control group, 2 of the 8 rats have died. The second death in the control group occurred on 1st December 2021, of natural causes. The animal's organs were preserved for future studies.

 

After the 4th dose of E5, tests for the inflammatory cytokines TNF-alpha and IL-6, as well as grip strength and body weight, were performed. The graphs

with the results are shown below.

 

TNF-alpha

 

 

IL-6

 

 

Grip strength

 

 

Body weight

 

 

The graphs above show that the rejuvenating effect of E5 — based on cytokine levels and grip strength — is maintained even after the fourth dose. The treated rats will be kept alive indefinitely with periodic doses of E5 (each dose is given every 90 days). It would be an interesting result if they outlive the control rats and surpass the 36 months average lifespan.

 

As for the pictures of the rats after the 4th dose of E5, the 6 remaining control animals and the 8 treated animals are shown below.

 

Control group

 

Treated group

 

 

[smithx]

Any link to the actual study? It looks like that copy/paste missed a lot of stuff.

 

Yuvan provided their update on the E5 lifespan study today.

 

 

[rodentman]

Any link to the actual study? It looks like that copy/paste missed a lot of stuff.

 

 

I made a copy of the email sent from the study here: http://placebox.net/E5/12-9-21/

 

I tried to paste the images to this message board, but they got removed.

[RWhigham]

"Dr Katcher's E5 Experiment, December 2021 Update"    This 3 minute 58 sec video from Modern Healthspan first reviews the project, then begins the update at 1 minute and 45 seconds.

Edited by RWhigham, 19 December 2021 - 08:02 PM.

[smithx]

Great! Thanks very much.

 

Those results actually look very encouraging.

 

 

I made a copy of the email sent from the study here: http://placebox.net/E5/12-9-21/

 

I tried to paste the images to this message board, but they got removed.

 

[rodentman]

Great! Thanks very much.

 

Those results actually look very encouraging.

 

Definitely.  It's starting to look unprecedented.    As crazy as it sounds, it's looking as if the rats are actually getting 'better' with age.... with the exception of weight.

[QuestforLife]

Let's talk about albumin

Lots of people seem bowled over by more shiny coats on the E5 treated rats, and the extension of average lifespan in the parallel plasma exchange experiment - but simple albumin infusions achieve this, and more.

They increased lifespan of mice ~20% in this study [1] injecting 1.5mg/g of body weight every 3 weeks.

And we know you can make a good human aging clock just looking at albumin concentration [2].

Albumin does not readily cross the BBB, and we know from the Katcher/Horvath 2020 rat study that the organ examined with least epigenetic rejuvenation was the hypothalamus [3]. Suggestive?

It's also interesting how many injections the E5 rats needed. 4 times on alternate days for 8 days! That's a lot. This eliminates E5 being a signalling molecule like GDF11 or Oxytocin, which would only require a small amount. If E5 were albumin, this would explain why they're having to go with an infusion for humans (injections would not be enough: there's up to 50g albumin/L in serum). Albumin infusions along with saline would also cause dilution of harmful factors in the blood like eotaxin.

But how does albumin itself cause rejuvenation? Glutathione upregulation and NF-kB downregulation inside cells. Glutathione can't get into cells, but albumin can [4] and is a ready supply of cysteine to those cells, being used by them to manufacture glutathione, which decreases NF-kB and other downstream inflammatory markers.

Regardless of whether E5 really is just albumin, albumin is a simple treatment that has profound benefits. If I were old and infirm I would be looking hard at getting such a treatment.

References

[1] https://www.biorxiv.....02.21.432135v1

[2] https://translationa...2967-017-1267-8

[3] https://www.biorxiv.....05.07.082917v1

[4] https://doi.org/10.1...m.162.4.9910106

Edited by QuestforLife, 22 December 2021 - 02:04 PM.

[rodentman]

Let's talk about albumin

Lots of people seem bowled over by more shiny coats on the E5 treated rats, and the extension of average lifespan in the parallel plasma exchange experiment - but simple albumin infusions achieve this, and more.

They increased lifespan of mice ~20% in this study [1] injecting 1.5mg/g of body weight every 3 weeks.

And we know you can make a good human aging clock just looking at albumin concentration [2].

Albumin does not readily cross the BBB, and we know from the Katcher/Horvath 2020 rat study that the organ examined with least epigenetic rejuvenation was the hypothalamus [3]. Suggestive?

It's also interesting how many injections the E5 rats needed. 4 times on alternate days for 8 days! That's a lot. This eliminates E5 being a signalling molecule like GDF11 or Oxytocin, which would only require a small amount. If E5 were albumin, this would explain why they're having to go with an infusion for humans (injections would not be enough: there's up to 50g albumin/L in serum). Albumin infusions along with saline would also cause dilution of harmful factors in the blood like eotaxin.

But how does albumin itself cause rejuvenation? Glutathione upregulation and NF-kB downregulation inside cells. Glutathione can't get into cells, but albumin can [4] and is a ready supply of cysteine to those cells, being used by them to manufacture glutathione, which decreases NF-kB and other downstream inflammatory markers.

Regardless of whether E5 really is just albumin, albumin is a simple treatment that has profound benefits. If I were old and infirm I would be looking hard at getting such a treatment.

References

[1] https://www.biorxiv.....02.21.432135v1

[2] https://translationa...2967-017-1267-8

[3] https://www.biorxiv.....05.07.082917v1

[4] https://doi.org/10.1...m.162.4.9910106

 

 

 

I'm a big advocate of Albumin infusions and blood dilution in general.   And I think it's been largely ignored by the anti-aging community which is unfortunate.    However, the results of these therapies are not on par with what we are seeing so far with E5.

 

it's tough to make a comparisons at this stage of the game... however, we can at least compare grip strength improvements between the two therapies.

 

The grip strength improvement of albumin infusions was 29.6% for females and 17.4% for males.  This is very impressive, and I don't want to trivialize this improvement.

 

However, E5 has shown an increased grip strength of 250%, which is unprecedented.  You have to remember, these rats are the equivalent of 80yo, and yet they have the strength of rats in their prime years.

 

I am still not suggesting that E5 is a cure for aging.... but I am saying E5 currently looks like its in uncharted waters for late-life interventions.

[QuestforLife]

The grip strength improvement of albumin infusions was 29.6% for females and 17.4% for males. This is very impressive, and I don't want to trivialize this improvement.

However, E5 has shown an increased grip strength of 250%, which is unprecedented. You have to remember, these rats are the equivalent of 80yo, and yet they have the strength of rats in their prime years.

The grip strength of the E5 treated female rats doubled from about 6 to 12N. That's a 100% increase. Still better than the 29% increase in the female mice treated with albumin. Assuming you can compare mice and rats. And assuming the methods were the same - from reading the descriptions they don't seem the same, and worryingly, the Horvath/Katcher paper makes no mention of the grip strength test being blinded. Also the sample size of the albumin treated mice was over 3 times larger than the E5 treated rats.

Yes, it's unlikely E5 is just albumin. But we can't make that determination from the comparison of grip strength measurements. Hopefully Harold will give us something more to go on soon.

Edited by QuestforLife, 23 December 2021 - 09:18 AM.

[QuestforLife]

I made a copy of the email sent from the study here: http://placebox.net/E5/12-9-21/

I tried to paste the images to this message board, but they got removed.

Can anyone explain why in the current experiment the rats' response to E5 as measured in the reduction of TNF-alpha and IL-6 is muted compared to the Horvath/Katcher paper from 2020?

For example the figure in your update shows a TNF-alpha reduction from about 95 to 70pg/ml after two doses (with 1 dose doing very little) whereas figure 6 here: https://doi.org/10.1...20.05.07.082917 shows a reduction from 120 to 50pg/ml after 2 doses (with 1 dose also being quite effective).

Il-6 comparisons are similar.


Have they changed the dose of whatever E5 is?

[RWhigham]

A July 2021 Article, An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging, says   "Notably, canonical markers of acute infection such as IL-6 and tumor necrosis factor-α were not major contributors to iAge,"  So it would seem IL-6 and TNF-α do not consistently track age all that well.

Edited by RWhigham, 23 December 2021 - 04:32 PM.

[RWhigham]

iAge is discussed further on Modern Healthspan in the Professor David Furman Interview Series. Dr. Professor Furman a project leader at the Buck Institute for Research on Aging and is director of the Stanford 1000 Immunomes Project.

Edited by RWhigham, 23 December 2021 - 07:54 PM.

[QuestforLife]

A July 2021 Article, An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging, says "Notably, canonical markers of acute infection such as IL-6 and tumor necrosis factor-α were not major contributors to iAge," So it would seem IL-6 and TNF-α do not consistently track age all that well.

I don't know much about iAge, but to me the spread looks too big to be useful. Just look at figure 5 - the whiskers on the box plot are about +/-20years for normal old and +/- 40years for the centenarians.

[RWhigham]

I don't know much about iAge, but to me the spread looks too big to be useful.

 iAge.jpg   35.74KB   1 downloads

Edited by RWhigham, 23 December 2021 - 10:05 PM.

[QuestforLife]

iAge.jpg

Where's that from, didn't see it in the paper?

Still a little skeptical. If that stark dividing line were really true then the 15 yo with a 20 yo iAge would be in a diseased state, but that 90 yo with a 45 yo iAge is healthy?

[RWhigham]

Where's that from, didn't see it in the paper

• iAge^®

Edited by RWhigham, 23 December 2021 - 10:45 PM.

[Bike_to_120]

I purchases the iAge test last summer. Still waiting for delivery of the test kit

[JamesPaul]

In response to "I don't know much about iAge, but to me the spread looks too big to be useful."

 

The large spread appears to be an indication that people of a given chronological age have very different inflammatory ages.

 

The first video in the David Furman series, starting around 7 minutes 45 seconds, Dr. Furman says there are "people in their 30s and 40s that show inflammatory ages of 65 or 70."

 

He goes on to say that they develop diseases normally seen only in people much older.

Edited by JamesPaul, 24 December 2021 - 09:39 PM.

[QuestforLife]

In response to "I don't know much about iAge, but to me the spread looks too big to be useful."

The large spread appears to be an indication that people of a given chronological age have very different inflammatory ages.

The first video in the David Furman series, starting around 7 minutes 45 seconds, Dr. Furman says there are "people in their 30s and 40s that show inflammatory ages of 65 or 70."

He goes on to say that they develop diseases normally seen only in people much older.

Yes, useful for indicating inflammatory state better than say, CRP or NLR, but large divergences from actual age indicate lack of correlation with biological aging, which is our primary concern.

Unless...a sustained elevated iAge then leads to accelerated aging (with verification by other clocks like methylation or telomere). That would be interesting, sort of like a early indication things were going wrong (basically a current rate of aging test rather than a biological clock).

[brian1965]

Update on E5.   

Rats are 32 Months Old, 4rth dose has been administered. 

E5 Rats Alive: 8

E5 Rats Dead: 0

Control Rats Alive: 6

Control Rats Dead: 2

 

I'm actually impressed with the control rats.. only 2 dead of old age at 32 months for this species is impressive.  I guess this is just a healthy lot.  I would assume December will bring a lot of rat deaths here.

 

I've attached an image

 

Just received a new update on the rats, dated 1/31/2022 -- surprisingly, no additional control or treated rat deaths.

 

Lifespan study updates

6 old control rats and all 8 old treated rats are still alive. New data (below) now shows a comparison with a young control group. The organs of the rats who died are being preserved for possible future analysis, including a biomarker of cellular senescence. New images of the rats are also available below.

 

 

Body Weight

 

 

 

 

Grip Strength

 

 

 

 

TNF-alpha

 

 

 

 

IL-6

 

 

 

 

Old control group

 

 

 

 

Old treated group

 

 

 

 

 

[brian1965]

New update on the E5 trial:  one more control rat has died.  That leaves 8 treated rats alive, and 5 control rats alive.

[QuestforLife]

Can anyone explain why in the current experiment the rats' response to E5 as measured in the reduction of TNF-alpha and IL-6 is muted compared to the Horvath/Katcher paper from 2020?

For example the figure in your update shows a TNF-alpha reduction from about 95 to 70pg/ml after two doses (with 1 dose doing very little) whereas figure 6 here: https://doi.org/10.1...20.05.07.082917 shows a reduction from 120 to 50pg/ml after 2 doses (with 1 dose also being quite effective).

Il-6 comparisons are similar.


Have they changed the dose of whatever E5 is?

 

After having asked Akshay about this, the answer appears to be that the earlier trial was done with male rats, the current lifespan trial is being done with female rats.

Edited by QuestforLife, 04 February 2022 - 03:36 PM.

[elfanjo]

One of the treated rats died :(

Here is the full email copy:

Updates about Yuvan Research
Yuvan and Johns Hopkins University establish a partnership

“We are happy to announce a research collaboration agreement with Johns Hopkins University, one of the most reputed Universities in the world of medicine”, stated Akshay Sanghavi, CEO of Yuvan. He added that “at JHU we hope to progress E5 from a crude biologic to a potent therapeutic with standardized doses. We have already mapped out our first year’s research work with their brilliant team and amazing lab equipment.”
New E5 study

To further understand the effects of E5, Yuvan is starting a new study that will be conducted in rats of both sexes and 18 months of age — the starting age of the male rats in the study published in May 2020 in bioRxiv. In this new study, it will be possible to clarify whether there are differences between the effectiveness of E5 in females and males.
Lifespan study

Regarding the lifespan study, the first death of a treated rat has occurred, so to date 3 untreated rats and 1 treated rat have died. Initially, there were 8 rats in each group.
NEEL gel

According to Sanghavi, “We are scheduled to go into production on the 14th of March due to raw material supply issues, so after batch testing and bottling, the orders should be shipped by the first week of April. We truly appreciate our customers' patience and will gift them a complimentary 30 ml bottle of NEEL gel for each bottle they purchased in return for their kindness and support."

Edited by elfanjo, 12 March 2022 - 07:47 PM.

[Frank Walter]

One of the treated rats died :(

Here is the full email copy:

Updates about Yuvan Research
Yuvan and Johns Hopkins University establish a partnership

“We are happy to announce a research collaboration agreement with Johns Hopkins University, one of the most reputed Universities in the world of medicine”, stated Akshay Sanghavi, CEO of Yuvan. He added that “at JHU we hope to progress E5 from a crude biologic to a potent therapeutic with standardized doses. We have already mapped out our first year’s research work with their brilliant team and amazing lab equipment.”
New E5 study

To further understand the effects of E5, Yuvan is starting a new study that will be conducted in rats of both sexes and 18 months of age — the starting age of the male rats in the study published in May 2020 in bioRxiv. In this new study, it will be possible to clarify whether there are differences between the effectiveness of E5 in females and males.
Lifespan study

Regarding the lifespan study, the first death of a treated rat has occurred, so to date 3 untreated rats and 1 treated rat have died. Initially, there were 8 rats in each group.
NEEL gel

According to Sanghavi, “We are scheduled to go into production on the 14th of March due to raw material supply issues, so after batch testing and bottling, the orders should be shipped by the first week of April. We truly appreciate our customers' patience and will gift them a complimentary 30 ml bottle of NEEL gel for each bottle they purchased in return for their kindness and support."

 

I can't understand how it is possible to talk about production dates right after an update of an unfinished research on mice.

[elfanjo]

The gel going in production is not what is being studied

Edited by elfanjo, 26 March 2022 - 07:19 AM.

[Harkijn]

NTZ has now provided a short update on E5, showing dr. Katcher perform a grip test with one of the rats. The E5 treated rats seem to be 2.5 times stronger than the control ones.

[elfanjo]

Also another treated rat has died.
This is turning out to be pretty much like dr Goya's experiment. The rats are looking good and younger, but then they die pretty much at the same time as the non treated rats even though they look much healthier.
So far out of 8 rats in each group 4 control rats and 6 treated rats are still alive.

Potent as it is this method does not seem to work for all organs.
Yet the level of rejuvenation shown in this experiment is astounding. We need to find out what is not working, can we address it by other means.

Wait and see

Edited by elfanjo, 01 May 2022 - 12:20 PM.