Until last year I used to learn from Dr. Harold Katcher and Akshay Sanghavi lab research at Josh Mitteldorf’s Scienceblog. But now news from them in 2024 AFAIK.
E5 has been so far a promising candidate as an antiaging compound but today noticing the late radio silence about it scares the devil out of me. Am I missing something I should know?. If any let it be good news please. Thanks.
I think @Paul_2.0 has been following this closely, he posted some info a little while ago and I think he also said somewhere that Harold and Akshay have split up on this effort:
Yes, that’s right. Harold and Ashkay are no longer working together. I’m on Intervene immune’s mailing list and they announced that they will be working with Harold. Harold also posted on his LinkedIn that this was case. It seems like a really decent partnership to me. There is supposed to be an announcement at some point in the future. Things can obviously change so we’ll just have to wait and see. If I hear anything else one way or the other I’ll let everyone know.
I had hope for this. E5 seemed interesting. Seems all but dead now.
If it is dead, I would hope katcher would open up on all the details so that others, including biohackers, can try to translate the research into more validation testing in animals and ultimately humans
Do we have any new updates?
Hi, and welcome. No, I haven’t heard anything since.
Josh Mitteldorf brings Katcher’s E5 to the forefront again in his latest blog on exosome rejuvenation:
Even though his project hasn’t moved along as fast as many of us expected and would have liked, Harold Katcher and his E5 results may have kick-started something big.
Exosomes; mitochondria; mRNA; Klotho/PF4; Immunis doing human trials using the entire secretome which they’ve manufactured, apparently in volume, from embryonic cells: all circulating in plasma and making youngish mice out of old mice.
There appears to be more interest every day in circulating plasma factors. Mentions here and there indicate that a central problem is acquiring or creating these factors in the quantities needed while meeting rigid quality standards. I don’t know much about bioreactors beyond the name, but isn’t that where this is headed?
Mitrix bio are part of this area. Oddly enough it strikes me that people need mitochondria that are good enough, but not necessarily the most efficient possible. Higher efficiency will change splices.
My opinion only; I would hope that identification and testing of the substances in these exosomes should be of the highest priority.
Interestingly rapamycin was better. I wonder, however, about the possibility of synergy here.
Hope so. I guess there is the possibility that everything we’re doing is just redundant. That would be sad.
They’re just centrifuging the plasma down, looks like they have a special machine. Couldn’t anybody buy one and start doing it? This must be the trouble Harold was having. Lawyers.
If @KarlT can buy pig blood for $2 /gal and then sell a weekly shot to somebody for $500, the machine will pay off pretty quickly. That’s what they’re doing with PRP and they don’t even have to buy the blood, they get it from the patient.
The issue of mitochodrial transplant which is behind all of this is quite complex. The energy efficiency of the mitochondria will drive splices. Splices are where a gene can produce different proteins dependent on the circumstances.
Hence if you have too efficient mitochondria you will not necessarily get the right proteins. I think getting new mitochondria is a good idea, but it needs to be done carefully if from external sources. Internally the body shares around mitochondria as a response to things like exercise. I think the HIF 1 alpha transcription factor drives a lot of mitochondrial sharing.
What Rapamycin should do is improve the average mitochondrial quality in any one cell (depending upon dosing). There is, however, a limit on mitophagy in that
a) Mitochondria in a cell can only be averaged up to best mitochondria in that cell.
b) Some damage to mtDNA can damage the mitochondrial effectiveness without reducing MMP and MMP is used to identify flawed mitochondria. Mutations to ATP Synthase fall into this category.
However, my view is that a lot can be done to improve energy levels and cytosolic acetyl-CoA levels as well as directly impacting on transcription levels. These use the body’s own systems and are, therefore, unlikely to be harmful per se. There do remain, of course, the issues about side effects such as Rapamycing reducing stem cell production.
My point about mitochondrial transplant is that it can in some circumstances be harmful.
I also think that longer lived species have better mechanisms for maintaining mitochondrial quality. Ignoring all the issues about the practicalities of taking pig blood to generate transplantable mitochondria there is the big issue as to whether the mitochondria are in fact ones you would wish in preference to your own mitochondria much that there would be a mix.
Xenomitochondrial transplant is probably more practical than most xenotransplants, but I have not read up on it and it would not be my first preference.
Mitrix Bio’s approach is I think quite interesting in that they take mitochondria from an individual and aim to grow more mitochondria from that and then return them to that individual.
There is actually a question even from human mitochondria as to compatability of mtDNA with nuclear DNA.
Are there even mitochondria floating around in the plasma? I thought we were talking about EVs.
EVs with mitochondria in them.
Thanks for the heads-up.
Someone had recently made a post on Harold’s linkedin page:
“Dear Harold,
Have you started your new company yet outside of Yuvan? Have human or dog trials started yet? Some of us would like an update.”
He answered the following:
“the new company is called LXR-VT Corp. We are working hard to meet the biggest challenges to making age-reversal universal (and not just for billionaires). We believe we’re on the right track.”