I can get access as a longevity medicine physician, I’d guess. Will need to see the details on how it needs to be drawn and how delivered to their lab (e.g. packed in dry ice), timing of draw until it needs to get to their lab.
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Yes - the doctor needs to do a blood draw, and the blood sample (about 8ml they tell me) has to be shipped by FedEx with dry ice. SapereX has a prep package for the blood that they send to their associated doctors. That is one of the factors that drives up the cost, unfortunately.
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I’d need to get the details, but I’m not convinced that one couldn’t get the blood draw by a phlebotomist and send it in. I’ll have to contact them if there is interest on the forum and I’m happy ordering this for individuals if there was a system setup to allow a sensible pattern of community collection. There is nothing magical by having me draw the blood - the phlebotomist can do the same thing.
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Is there an explanation as to how senescence in other tissue cells can be picked up in the blood?
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This is a fairly long article with lots of reference material for anyone interested. For about 3 years I read 2 to 3 studies on senescence every day. Well maybe not every day but I have bookmarked over 200 that I’ve read 
and I’m convinced that as indicated in more than 1 study and in articles on the 12 Hallmarks of Aging where senescence is identified as the #1 issue to resolve for living a more more disease free life.
In the mean time I’ll be doing a cycle of FOXO4-DRI in Jan
To advance, we must have clear and ideally distinct single or combinations of markers for senescence that would identify whether it is skewed to a detrimental or beneficial response clinically. Significant resources are being placed in this area, such as in the creation of The National Institutes of Health (NIH) Cellular Senescence Network (SenNet) Consortium (SenNetT)187. SenNet aims to map senescent cells using single-cell technologies across mouse and human lifespans in multiple tissues
Emerging insights in senescence: pathways from preclinical models to therapeutic innovations
https://www.nature.com/articles/s41514-024-00181-1
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The field needs to try to.answer the question as to where most senescent cells come from. I dont think it is replicative senescence. Instead it is the failure to differentiate.
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The hidden role of senescent cells in ageing and organ dysfunction
The study introduces a “senescence atlas” mapping the distribution of these cells
This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population.
https://www.nature.com/articles/s12276-024-01354-4
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The immune system can distribute mitochondria.
Jay
#252
Steve_Combi, I’m glad you’re reporting on this. I have not heard much about FOXO4-DRI for several years, but it sounds great if it works without any bad side effects. Good luck.
There used to be a YouTube video of Dr. Darren Moore doing a self experiment with FOXO4-DRI (shown below), but I can’t seem to get it to work. And, there used to be a website https://foxo4dri.com/ which also seems to no longer work. Information seems to have grown dim since 2018 or so. I wonder why? I provide the information in case someone knows of updated versions that do work.
And, one more note which if already posted, I apologize. Cleara Biotech can provide some more information about FOXO4-DRI , though not enough, at this website: History | Cleara Biotech
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I first became interested in this one in 2019 and have read a fair bit about it. I’ve been “watching” others using this and have not “seen” any bad reactions expressed by other bio-hackers. So I figured it was finally time to try it
One question I’ve seen people ask is about the “second generation” when when will it be available? as they are not aware it’s already available. And it is … FOX04-DRI
To date, several second generation senolytics have been produced including the D-retro inverse (DRI)-isoform of FOXO4, the FOXO4-DRI peptide (Baar et al., 2017). This peptide was initially developed when FOXO4 was found to be highly expressed in senescent cells, but not in healthy cells (Baar et al., 2017). The peptide works by interfering with FOXO4-p53 binding, causing nuclear exclusion of p53 and consequently the specific mitochondrial-induced apoptosis of senescent cells (Baar et al., 2017)
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Jay
#254
Steve_Combi, I almost forgot. Here is a link to information you’ve likely already read about FOXO4-DRI, but in case not here it is: How to Plan and Carry Out a Simple Self-Experiment, a Single Person Trial of Senolytic Peptide FOXO4-DRI – Fight Aging!
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Curious
#255
A new senolytic approach that effectivly might rejuvanate the immunsystem. Looks promising.
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I have read that a few times over the years that I’ve been thinking on the FOX04-DRI senolytic. It’s a pretty rational approach. There are a few steps I’m not concerned about though. All the how to get it, use it, price it, etc is not a concern these days, there is a lot of that in there
The “tests” are mostly safety related, few of them will provide any real data on if senescence cells are cleared but these tests are proxies that should improve. Which is fine with me.
I just had a hormone panel done and my regular tests so I have that baseline. From last year to this one my HDL (the only one of 27 that was not in range) is now in the normal range and my results were even better than last year, which was the best I’d seen in 15 years. All my hormone results were “perfect”, this is the first time I’ve had that panel done as I’m interested in TRT but will probably go with hCG instead as a result of the hormone tests results. I’m low normal in those.
I also don’t think the dose in that write up is what I’m going to do. I’m more of a low and slow experimenter LoL!
I’m going to go with 3mg x 6 doses. One dose every other day. Will be starting that tomorrow.
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The immune system, when robust, can deal with excess senescent cells but that ability declines as we age. One of the reasons I like the TRIIM protocol. Gotta keep those T-Cells educated of they go off all williy-nilly causing problems as we age.
The idea of a vaccine type treatment is also one of the ideas going around.
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Curious
#258
And when it comes to immune function among older persons, we have the study that Joan B. Mannick did. For me that study is a proof of concept that intermittent imhibition of mTOR has a meaningful impact in the dysfunctional human immune system of older persons.
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Jay
#259
It sounds like you’re going about it the right way and I hope it turns out to be successful. It could be something I would try if I ever get enough information from people who have tried it. I’ve asked about this on other sites and the best answer I can get is something like “It’s great” without any details about why it’s great which isn’t very helpful. Either way, good or bad, please report back when possible.
As a side note, I know you’ve done the research, but have you ever approached injections with very small test amounts in the beginning before going into a standard protocol? For example, maybe 0.25 mg or 1 mg instead of starting at 3 mg. You don’t need to reply. I’m just presenting an idea from a very cautious person’s point of view.
I’m going to be looking for visible changes, like skin tone, hair “restoration”, basic functionality, arthritis in my left little finger.
I’ll be getting that hormone panel done again in 3 months. In mice it restored Test production in aged mice. To get those tests I had to sign up with a HRT clinic and get a prescription for Test. I won’t take any until this experiment is done.
And I’m thinking I will change my Trudiagnostic testing from every 9 months to every 6 months.
A lot of people have blazed the trail on this one and I’ve not seen any bad reactions reported.
As far as easing into a new experiment, I usually do that. I have found that I’m mostly insensitive and don’t have any adverse reactions to any of the peptides I’ve tried so far, and I have eased into most of them.
The “recommended” dose for FOX04-DRI is based off the mouse doses which indicates 2 large doses a day apart, annually or semi-annually. And by large, those are 25mg doses for humans. So… in effect 3mg every other day for 6 doses (18mg total) is easing into it
Depending on how this cycle goes with the measurements that I can get done over the next 6 months and how we feel (my wife is participating as well) I may up that or leave it alone.
I was at the lab today and decided why wait any longer and we took our first dose today.
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JuanDaw
#261
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12458
This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.
To determine whether senolytic treatment with D+Q reduces senescent cell burden and improves vascular function and structure in a model of atherosclerosis, ApoE−/− mice were fed a Western diet (TD88137; Harlan Teklad) for 4 months to allow development of established atherosclerosis (Dansky et al ., 1999). Vehicle or D+Q was then administered once weekly (i.e., oral gavage with a dasatinib (5 mg kg−1)/quercetin (10 mg kg−1) cocktail) for the next 2 months (i.e., months 4–6).
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Looks like an interesting marker. Now we need an inexpensive test to help in the possibility of maintaining a “healthy” level of senescent cells, i.e. The Threshold Theory of Senescence. There is a reliable and accurate way to measure IL-23R, whether it’s readily available for a reasonable price, I don’t know yet.
We discovered that age-dependent changes in plasma proteins, including IL-23R, CCL5 and CA13, were reversed by senotherapeutics, which corresponded to expression differences in tissues, particularly in the kidney. In plasma from humans across the lifespan, IL-23R increased with age. Our results reveal circulating factors as candidate mediators of senescence-associated interorgan signal transduction and translationally impactful biomarkers of systemic senescent cell burden.
IL-23R is a senescence-linked circulating and tissue biomarker of aging
https://www.nature.com/articles/s43587-024-00752-7
Started FOXO4-DRI on Sunday. 12MG Daily for ten days. So far no side effects, I am adjusting the pH with sodium bicarbonate as it is a bit acidic.
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