HIV Drug (Maraviroc) Reverses Muscle Aging by purging “Zombie Cell” Signals

News
#10

I didn’t see anything about memory, don’t remember it anyway.

2 Likes
#11

:slightly_smiling_face: Maraviroc Fights Middle-Aged Memory Loss (And Muscle Aging)

4 Likes
#12

I’m not a big fan of senomorphics, I’d rather clear senescent cells out entirely. Well not really entirely as this is not possible any way. But I don’t want cells left behind that are “damaged” enough to enter the state of senescence and possibly ready to become senescent again, once the senomorphic compound is no longer present.

Hit and run.

I’ll stick with FOXO4-DRI for now, as it works in more tissues than just muscles.

1 Like
#13

@RapAdmin and others, did we establish the dose to be about 30mg daily for 3 months (based on the studies) for improving muscle function/mass? and maybe repeat it annually, or was it something different?

1 Like
#14

Yes - thats what AI suggests is the translational dose. Of course this was just a single study, so we don’t know if there is a dose-response effect (e.g. higher might be better), and only for 3 months (longer might be better, 3 months might have just been chosen for convenience or funding of the study).

It’s early, so the optimal schedule and dosing is still anyone’s guess. If I were to get my father on this, I’d probably try a higher dose just because it’s easier when it comes to pill splitting. The pills are typically 300mg, Its pretty easy to “1/4” pills, but beyond that you start getting a lot of fracturing of tablets and its hard to know what the amount is in any given fragment, so perhaps trying 75mg per day (or every two days). And track grip strength, etc. before and after (and during) to see progress.

5 Likes
#15

Agreed and makes sense.

#16

Equivalent dosing might mean more than a 57 mg dose every 2 days. 2 mouse days are how many human days?

  • Human Equivalent Dose (HED):
  • Animal Dose: 10 mg/kg (administered every 2 days).
  • Math: 10 mg/kg×(3/37)≈0.81 mg/kg.
  • Human Result: For a 70 kg human, this is ~57 mg (every 2 days) or roughly 30 mg/day.
  • Note: The standard clinical dose for HIV is 300 mg BID (600 mg/day). The longevity/sarcopenia effective dose appears to be ~1/20th of the antiviral dose, suggesting a wide therapeutic window.
2 Likes
#17

Good Point!

From Gemini:

This is a crucial translational insight. You are correct to flag this: “Every 2 days” in a mouse is biologically distinct from “every 2 days” in a human.

When we strictly apply allometric scaling (adjusting for metabolic rate and body surface area), we usually scale the amount of the drug. However, we often neglect to scale the time (chronopharmacology).

Here is the deep-dive analysis on why the frequency should likely be adjusted, and the specific “Affinity Gap” that suggests the human dose could be even lower than calculated.

1. The “Time” Problem: Pulse vs. Sustain

Drugs clear from the body much faster in small animals.

  • Mouse Half-Life () of Maraviroc: ~1 to 2 hours.
  • Human Half-Life () of Maraviroc: ~14 to 18 hours.

The Mouse Experience (The “Sawtooth” Effect):
Because the mouse metabolizes the drug so quickly (), dosing every 48 hours means roughly 48 half-lives pass between doses.

  • Result: The drug is effectively 100% cleared from the mouse’s system for the vast majority of the 2-day window.
  • Mechanism: This confirms Maraviroc acted as a “Hit-and-Run” Senomorphic. It briefly pulsed the receptor, disrupted the inflammatory signal loop, and then vanished. It did not provide continuous coverage.

The Human Experience (if dosed every 2 days):
With a 16-hour half-life, dosing every 48 hours means only 3 half-lives pass.

  • Result: At the time of the next dose, a human would still have roughly 12.5% of the previous dose circulating in their blood.
  • Implication: Dosing a human every 2 days results in sustained, fluctuating coverage, whereas the mouse got intermittent spikes.

Correction Strategy:
To mimic the “washout” period seen in mice (allowing the immune system to reset and avoiding constant suppression), a human might actually need less frequent dosing.

  • Strict Mimicry: To achieve the same “drug-free” interval as the mouse, a human might only need to dose twice a week (every 3-4 days).

2. The “Affinity” Problem: The Human Advantage

There is a massive hidden variable in this study: Maraviroc was designed for Humans, not Mice.

  • Human CCR5: Maraviroc binds with high affinity (binds tightly).

  • IC50 (Inhibitory Concentration) 2 nM (Nanomolar).

  • Mouse CCR5: Maraviroc binds with low affinity (binds loosely).

  • IC50 3600 nM.

The “Affinity Gap” Calculation:
The drug is roughly 1800x less potent against the mouse receptor than the human receptor.

  • Interpretation: The researchers likely had to use a relatively “high” dose (10 mg/kg) in mice just to force the drug to stick to the mismatched mouse receptors.
  • Correction: In humans, where the drug fits the receptor perfectly (“lock and key”), we likely need significantly less drug to achieve the same biological effect.

3. The Optimized Translational Protocol

Combining the Pharmacokinetic (Time) difference and the Affinity (Potency) difference, we can refine the protocol.

The “Safe” Protocol (Standard BSA Extrapolation)

  • Dose: 30 mg / day (or 60 mg every 48 hours).
  • Frequency: Every 2 days.
  • Logic: This is the conservative, “dumb” translation. It provides higher coverage than the mouse study but is well within safety limits (1/10th of HIV dose).

The “Bio-Mimetic” Protocol (Adjusted for Biology)

  • Dose: 15 mg - 30 mg (Low Dose).
  • Frequency: Twice Weekly (e.g., Monday/Thursday).
  • Logic:
  1. Lower Dose: Accounts for the 1800x better binding affinity in humans.
  2. Lower Frequency: Accounts for the longer human half-life, allowing the “washout” period that mimics the intermittent nature of the mouse study.

Summary Visual: The Exposure Mismatch

Variable Mouse (The Study) Human (Standard Translation) Human (Optimized Translation)
Dose 10 mg/kg ~0.81 mg/kg ~0.2 - 0.4 mg/kg
Half-Life ~1 Hour ~16 Hours ~16 Hours
Dosing Interval 48 Hours 48 Hours 72 - 96 Hours
Receptor Status Pulsed (On/Off) Sustained (Always partially blocked) Pulsed (On/Off)

Recommendation:
Given the goal is Senomorphic (breaking the signal) rather than Antiviral (100% blockade), the Twice Weekly protocol at a low dose (30mg or equivalent of a split tablet) is theoretically superior. It maximizes safety (liver/immune) while replicating the “pulsed” mechanism that reversed the sarcopenia.

5 Likes
#18

A 70 kg human dose of 30 mg Monday and Thursday would require splitting tablets into pretty small pieces: a 150 mg tablet cut 5 ways.

Grapefruit juice ought to jack up the dose. Do Drs. Gemini and Grok know by how much? If it increases the dose as much as with rapamycin, you’d cut the 150 mg tablet 18 ways.

1 Like
#19

There are no commercially available pill splitters that simultaneously cut a pill into more than four pieces (i.e., there is no “pizza cutter” that stamps a pill into 8 wedges in one motion).

To achieve 1/8th doses, you must use a high-precision splitter to cut the pill sequentially: first into halves, then quarters, then eighths. Most cheap plastic splitters fail at this stage because they crush the small 1/4 fragments rather than cutting them.

The following commercially available products are capable of cutting into 1/8ths, listed by effectiveness rather than marketing claims.

1. The Top Tier (Best for Accuracy)

These are the only tools reliable enough for 1/8 splits on small or brittle pills. They use opposing blades or advanced centering to prevent the pill from crumbling.

  • Equadose Pill Splitter (V2)
    • Mechanism: Uses twin opposing blades that indent and “crack” the pill apart rather than a single guillotine blade that crushes it.
    • Why it works for 1/8: The open design allows you to see exactly where the blades contact the pill. You can position a tiny 1/4 piece precisely between the blades to split it into an 1/8.
    • Pros: Handles odd shapes and tiny fragments better than any enclosed box.
    • Cons: Expensive (~$30+); no collection box (pills stay on the table).
  • EqualSplit
    • Mechanism: Similar opposing blade concept but housed in a more traditional aluminum body.
    • Why it works for 1/8: The metal construction provides rigidity that plastic flexes out of. The opposing force creates a cleaner break on small fragments than a single-blade plastic cutter.
    • Pros: Durable; typically cleaner cuts than pharmacy-brand plastic cutters.
    • Cons: You must manually center the small pieces carefully.
1 Like
#20

Then maybe an extended hit & run strategy, splitting a 150 mg pill 4 ways for a 37.5 mg dose once a week. We’re guessing anyway, so the extra days might even be better.

Since this does require continuous use to benefit, 1 pill a week wouldn’t add much complication to one’s routine.

I do wonder about stomach acids destroying the drug if the pill is split. Is it like rapamycin in that regard?

3 Likes
#21

Grind the pill into powder.
Separate into as small a dose as you like.

3 Likes
#22

Kelman, I’ve checked the sources advertising low prices like $13.00. All of the sources I asked provided prices per bottle around $100.00 or more. The low prices being shown may be errors or an advertising gimmick.

3 Likes
#23

Is there a grinder for this purpose that you know of?

1 Like
#24

Get a small, lab-grade porcelain mortar and pestle, such as the Cole-Parmer AO-63100-61 Mortar and Pestle Set, Porcelain, 50 mL, from Amazon (~ $18). I bought a larger stainless steel one, but I don’t like it as much, as the powder from crushing tends to cling to the sides and is harder to remove. Also get a small milligram scale (Digital Milligram Scale 50g x 0.001g, Mini Precision Scale) for ~$13.

5 Likes
#25

Important to note that CCR5 is a critical but not sole driver of muscle aging via SASP. The authors reinforce this: The CCL3/4/5-CCR5 axis amplifies SASP (inflammation, niche disruption), but senescence involves a network (e.g., NF-κB, AP-1 TFs like JUNB/ATF3; other SASPs like CXCL8/IL6/TGFB1). Heterogeneity across cells and multiple pathways (e.g., ECM remodeling, growth factors) means no single driver dominates.

Also, no specific data exists yet on gut impacts in non-HIV contexts like sarcopenia or aging. (Virtually every ingested drug may impact the gut microbiome as we are learning that it has an “elephant memory.”)

3 Likes
#26

Maraviroc (300mg twice daily) plus pravastatin (10mg once daily) for 6 to 12 weeks form the basis of Dr Bruce Patterson’s Long COVID (PASC) protocol, which is theorized to interrupt the monocytic-endothelial-platelet axis and restore immune dysregulation in that condition.

4 Likes
#27

How are you taking this and what dose
are you doing. It looks like you have to inject it

1 Like
#28

It sounds like you would just take a break from the two pills so you won’t be doing them at the same time. Maybe do a month loading of this then do it maybe one a month and take that week off from the rapamycin? Any thoughts are good.

1 Like
#29

Our dose schedule for FOX04-DRI

Yes it is a subQ injection. I’m a bit of a peptide junky and with our current morning and night cycles we are doing 8 - 9 injections per day.