According to this Chinese paper, a klotho-derived peptide, KP-1, reverses the damage of fibrosis and thus preserves kidney function. Klotho is a key to healthy aging but dosing and sourcing remain a bit uncertain.
https://www.nature.com/articles/s41467-022-28096-z
SS-31 is another peptide that has a positive effect on renal function.
24mg over a 3 day = 8.0mg per day
Twice a year.
For the 2 of us that is 48mg and at typical “retail” internet prices, that would be over $1k USD for 2 people, per cycle so for most people it would be cost prohibitive.
Overall I’m reasonably healthy for 70, my wife even more so.
Like many things, not much difference in how we “feel” and since most of our markers are already in the normal ranges, not much to discern from that.
Also take into consideration that we were doing a zombie killing protocol with D + F and a few other things, cycling that at very high doses (based on the 2 Phase 1 trials), every 3 months for the previous 4 years.
I’m ordering 1.0gm in a couple weeks and will up the dose a bit and do 3 cycles per year and have some inventory on hand 
Thank you for sharing your dosing protocol!
What benchmarks will you be tracking to help you evaluate FOX04-DRI safety and effectiveness?
I look forward to hearing how you and your wife react to it!
How has this been going with you? Are you still subQ’n foxo4-dri?
Since we had previously been doing an aggressive senolytic protocol since 2020, prior to switching to FOX04-DRI, not al lot has changed.
I consider it more of a prophylactic procedure.
Yes twice a year
Steve, I would really like to chat with you about FOXO4-DRI. I did a pretty deep research summary dive on it. i’m not allowed to upload since I’m a new user, LOL. I just joined to talk about this.
My dosing calcs based on standard surface area scaling put the correct dose at 20 - 30 mg per alternating day, for 6 - 11 total doses. I want to understand how you got to your doses and protocols.
My Dosing Notes
There have been no clinical trials in humans. The only mammal trials are for mice at 5 mg/kg. A 5 mg/kg dose in mice converts to a human‑equivalent exposure of about 0.4 mg/kg when you apply standard body‑surface‑area scaling (Km mouse 3, Km human 37), so: 5 mg/kg × (3/37) ≈ 0.4 mg/kg. For a 150 lb (≈68 kg) human, that’s roughly 0.4 mg/kg × 68 kg ≈ 27 mg, on the order of 25–30 mg total.
Protocol Notes
In the mouse trial q48h pulsed model over ~3 weeks and ≈11 total pulses, the first several injections (roughly the first 5–6 doses) likely do most of the meaningful work: they trigger apoptosis in the bulk of the senescent cell population, allow immune clearance of apoptotic debris, and sharply reduce SASP signaling. As the senescent pool shrinks, each subsequent pulse is hitting a smaller, more resistant fraction, so the marginal senolytic gain per dose probably falls off while the tissue is increasingly busy with remodeling and repair. That’s why, mechanistically, you’d expect diminishing returns after the early pulses—the biology has already been pushed toward a new, lower‑senescence equilibrium, and any further q48h hits are more about incremental cleanup than step‑change effects.
Based on this thinking the proposed protocol is q48h × 5 pulses of 20 mg = 100 mg total. This protocol is somewhat conservative in dose with 20 mg instead of 30 mg, and with only 5 pulses instead of 11. It falls far short of the appropriate design for a clinical trial safety test that might use 3 pulses of 0.5 mg each to test safety in humans before proceeding with incremental higher doses. But, we do have anecdotal safety data with some reports of research subjects experimenting with 1 mg – 5 mg for several pulses, with no immediate negative health outcomes. Of course, we have no long term tracking for these research subjects so we have no idea about long term risks, e.g. cancer.
I’m really interested in this therapy. But I’ve heald off becuase of all the known unknowns.
Your guess is as good as mine
It seems like a pretty safe peptide, which is a factor to consider.
As Yoda says, do or do not, there is no try. So I just do, with some consideration.
There is no easy way to quantify a “result” with any senolytic in humans, in a measurable way. I do feel better today than I did 4 years ago, which I attribute to the effects of the various peptides I take and especially Tripeptide and Retatrutide in enabling me to get to and maintain my ideal weight. Then there are the other 8 or 9 peps I take on a regular basis.
While I should probably do more testing, I’m a busy guy and have other things I’m focused on. As long as my semi-annual blood panel is good or improving, which it is, and I have no health issues of consequence, which I don’t, I’m happy.
I’ve seen kits of 10-mg vials available for $375, which still ain’t cheap, especially since you haven’t observed any positive effects, only the absence of negative ones. which may be all we can expect.
If I felt like this was safe, I’d do it in a minute. From the science it is scary as heck. Mechanistically plausible effects include leaky arteries and veins,and accelerating cancers that would otherwise stay latent. So many known unknowns with this one.
I’ve got a long research deep dive, but don’t know how to post it. I’m a new member with restrictions.
I’d maybe start a new thread. I will join because I’ve an interest in senolytics.
I have bumped up your status, please try to post it.
This is a paper on the impact of retatrutide on kidney function : The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity - PMC
This is based on phase 2 clinical data. Here’s how this aligns with the strategies mentioned by the paper above (summary courtesy of AI) :
1. Mitigation of “Inflammaging” and Oxidative Stress
The first paper identifies chronic systemic inflammation and oxidative stress as primary drivers of kidney dysfunction. The retatrutide study demonstrates that this triple agonist significantly reduces Urine Albumin-to-Creatinine Ratio (UACR)—a key marker of kidney damage—by up to 43% in patients with type 2 diabetes and 26% in those with obesity.
2. Targeting Mitochondrial Health and Metabolism
The first paper highlights mitochondrial dysfunction as a “pillar” of aging. Retatrutide’s unique inclusion of glucagon receptor agonism specifically targets metabolic efficiency.
3. Preserving Renal Function
The review paper focuses on the kidney as a model for aging, emphasizing the need for therapies that preserve the Estimated Glomerular Filtration Rate (eGFR).
4. Systemic Risk Reduction
The inflammaging paper argues for multimodal therapies that address multiple age-related diseases simultaneously.
Why were these EGFR increases considered “clinically insignificant”?
The paper provides several reasons why these small increases in eGFR are viewed positively or neutrally rather than as a sign of kidney stress:
I don’t understand this, it’s highly selective and has no effect on cells that are not in a state of senescence. The DRI aspect of this peptide matters.
I think having a high level of senescent cells is scary, compared to reducing them and the SASP they secrete.
Off the top of my head, keep in mind a couple facts,
Senescent cells have an effect on 8 of the 12 Hallmarks of Aging. The next closest one is Mitochondrial disfunction with an effect on 7 of the Hallmarks.
Reducing senescent cells to a “healthy level”, the Threshold of Senescence, is proposed as one of the better way to increase Health Span.
I have no interest in the “life span” debates. I’m only interested in being healthy until I die.
Amen, brother.
A chronic, sterile (non-bacterial) inflammation that increases with age. It is predicted by markers like IL-6 , TNF-α , and CRP .
I wonder when I see these associations, does is follow that low hsCRP implies low kidney inflammation?
The issue is that in the research the past few years they’ve discovered that there is a lot of variation in the types of senescent cells, in different organs, etc. So you can’t have a generic “senolytic”… there will be many, and this is where the companies are moving. See this presentation: Highlights from the 2023 Longevity Summit - #4 by RapAdmin
I just started a new tread in the forum dedicated to a FOXO4-DRI discussion. I posted my research summary deep dive into FOXO4-DRI. It is obviously a fascinating idea and the mouse study was really attention grabbing.
But there a bunch of ways senescent (and senescent appearing) cell apoptosis can kill you. Mostly we do not know much. As much of the biology as I understand is in the note I posed in the new thread.
Let’s continue any discussion there. I’d love to be just a little less convinced the unknown risks do not justify the unknown benefits.
