What an amazing interview. The speaker (Dena Dubal, MD, PhD) is one of the world’s foremost researchers on Klotho and is an excellent communicator/speaker.
I haven’t quite finished the podcast, but one question I have is the following:
Given that 1) Klotho doesn’t cross the blood brain barrier and instead uses platelet factor 4 (PF4) as one of its messengers to actually carry out the effects of Klotho in the brain, and 2) injecting PF4 in the periphery will do the same thing as Klotho since PF4 DOES cross the BBB and acts directly in the brain.
Why are they still studying Klotho instead of just using PF4?
Later in the podcast the interviewee explains that klotho still works even if pf4 is blocked so it seems there are redundant messengers or other mechanism of action. So using PF4 may not deliver all the value.
Honestly, the interview had me thinking about how i could get my hands on the stuff today, even if the safe thing to do is to wait for human research.
It’s tempting to jump right in, isn’t it? Sometimes we want to gamble and take the risk before the data arrives. However, more times than not, the hype cannot live up to the reality. But, I always hope that it does anyway.
Yes, I’d heard the the part about the redundant pathways, but she made it sound like PF4 did everything klotho did, but maybe only in regard to cognitive enhancement and not all the other things.
Attia also mentioned later that there’s a theoretical concern that enhancing PF4 might increase platelet adhesion and therefore promote clotting, so maybe they figure it’s safer to give klotho and let the cells determine how much PF4 to secrete rather than risk dumping in too much PF4.
I’ve been interested in klotho since Liz Parrish talked about it 4 or 5 years ago.
Here is a research chemical source for the klotho peptide. It’s quite expensive
Product Specific Information
This peptide corresponds to 16 amino acid peptide near the center of human KLOTHO.
PEP-1192 can be used as a blocking peptide with polyclonal antibody PA5-21078.
Target Information
KLOTHO is the systemic anti-aging hormone within the glycosidase1 superfamily. It encodes a type I membrane protein that is abundant in the kidney and brain. In mice, a deficiency in KLOTHO expression leads to various systemic phenotypes resembling human aging such as arteriosclerosis, osteoporosis, and skin atrophy together with growth retardation, short life-span and infertility. Transgenic mice overexpressing KLOTHO have an extended life span by inhibiting insulin/IGF1 signaling. KLOTHO is involved in the regulation of calcium/phosphorus homeostasis by inhibiting the synthesis of active vitamin D and identified as a potential tumor suppressor.
I’ve been taking it for about 3 years.
I’ve posted about it on other threads.
Of course, I have been “scolded” for this by certain narcissistic MDs who think they are the only ones allowed to voice an opinion.
It’s actually extremely cheap when you consider the dilution factors.
I’m excited about the possibilities of this line of inquiry. However, there are weaknesses beyond the obvious unspecified limitations of the mouse/human barrier in this growing chain of purported causality. I’m going to read more to see if these issues have been addressed but perhaps not fully addressed in communications. Given how territorial research has become, it is also possible that the unaddressed areas are the subject of someone else’s research.
That seems like a surprisingly low purity level. And yes - you should want to know what is in the other 10%. Typically I believe that when you see pharmaceutical grade purity of injection formulations like this it is well over 95%:
ACS grade meets or exceeds purity standards set by the American Chemical Society (ACS). This grade is acceptable for food, drug, or medicinal use and can be used for ACS applications or for general procedures that require stringent quality specifications and a purity of ≥95%.
Reagent grade is generally equal to ACS grade (≥95%) and is acceptable for food, drug, or medicinal use and is suitable for use in many laboratory and analytical applications.
For purified peptides, the main contaminants are deletions and truncations of the parent sequence . This occurs when the reaction efficiency of the incoming amino acid is reduced due to factors such as steric hindrance and secondary structure of the growing peptide chain.
Deletions and shortened versions of the target peptide are unlikely to be toxic or harmful IMO.
I have been taking klotho for a few years, it definitely has a strong effect on the brain as well as the body. I am not sure where you would even get PF4 and not sure I would want to inject it if you could source it.
Klotho on the other hand is available and there is a history of people using it for at least 4+ years. So I would stick to klotho, the safety history is there and the doses have been figured out and it is effective.
Thanks for sharing that. May we ask where that dose comes from? I ask because in the Attia podcast above, I think Dr. Dubal mentioned 1 microgram/kg body weight as the smallest effective sub-Q dose in mice. For a 70 kg human, that’s closer to 70 micrograms per dose*, which would be the whole vial. A picogram dose is orders of magnitude different from what she described.
*not an accurate conversion from mouse to human dose, but within an order of magnitude.
