The Culprit of Aging - Helen Blau's work at Stanford / PGE2, 15-PDGH

#81

Excellent idea. Please use all your influence to make it happen.

#82

someone msg bryan johnson this

i bet he will be willing to do the n=1 exploratory clinical trial phase 2-3 via tiktok for us

#83

A new study out of Helen Blau’s lab at Stanford:

Rescuing Muscle on Ozempic: 15-PGDH Inhibition Restores Regenerative Capacity During GLP-1 Weight Loss

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are highly effective pharmacological tools for weight reduction but consistently induce significant skeletal muscle attrition. While resting muscle strength and specific force might remain stable under GLP-1 RA treatment, the physiological deficit manifests acutely during muscle repair and hypertrophy. A recent study reveals that semaglutide drastically blunts the proliferative capacity of resident muscle stem cells (MuSCs) during tissue regeneration following an injury.

To counteract this regenerative failure, researchers utilized a pharmacological inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH). 15-PGDH functions as a “gerozyme” that degrades prostaglandin E2 (PGE2), a crucial lipid messenger required for stem cell expansion and muscle repair. By co-administering the 15-PGDH inhibitor (PGDHi) alongside semaglutide in diet-induced obese mice, researchers successfully rescued MuSC proliferation and restored regenerating myofiber size.

Critically, the 15-PGDH inhibitor achieved this localized anabolic rescue without compromising the potent fat-loss, systemic metabolic, and appetite-suppressing benefits of the GLP-1 therapy. Furthermore, semaglutide provided a secondary protective effect by preventing pathological calcification and fibrosis during the muscle healing process, a benefit that remained intact during PGDHi co-administration. This introduces a highly synergistic pharmacological strategy: utilizing a GLP-1 RA for robust metabolic correction while deploying a PGDHi to maintain stem cell resilience, structural tissue integrity, and functional strength. [Confidence: High]

Source:

Impact Evaluation: The impact score of this journal is N/A (Preprint Server),

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#84

Saw a study the other day which I cant find which suggests glp 1 agonists were protective of cartilage independent of the weight loss effect - in fact it was suggesting that cartilage thickened. So put pgdh-15 inhibitors together with glp 1 agonists then have you got a heavenly match for cartilage?
This study isnt the one im looking for but its close.

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#85

The ethanolic extract in the studies was 50% ethanol. An extraction made with pure ethanol was ineffective. I made 50% ethanol by mixing 190 proof Everclear vodka with water in a 10 to 9 ratio. I put this in a double boiler with jackfruit leaves and let it simmer for several hours, poured off and reserved the liquid, added more 50% ethanol and repeated. Then combined the liquids.
The non water soluble components precipitated out of solution. I could have continued concentrating the extract until I had a dry powder, but decided to stir well and drink a half ounce of the liquid at a time. After a few days I can confirm it has had one hell of a placebo effect. Maybe more than that.

Commercial availability of the dried extract could take less than a year.

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#86

I’ll buy it! Heres the a piece on the study i couldnt find… Semaglutide May Reverse Damage Caused by Osteoarthritis, Study Suggests : ScienceAlert

#87

A new National Geographic Story on Helen Blau’s research:

Doctors have long said cartilage can’t regenerate. They’re now rethinking that.

New research suggests injured joints may not be as permanent as once believed, opening fresh strategies to fight osteoarthritis.

Cartilage rarely gets attention—until it begins to fail.

For decades, arthritis patients have heard the same verdict: When cartilage wears away, it does not grow back. Unlike many tissues in the body, cartilage has little blood supply, which limits its ability to repair itself after injury. That biological limitation helps explain why osteoarthritis— caused by the gradual breakdown of cartilage—affects one in five adults in the United States and remains a leading cause of disability worldwide.

With no approved drug able to slow or reverse the disease, treatment typically focuses on managing pain and maintaining mobility through physical therapy. When damage becomes severe, the remaining option is often joint replacement surgery. The prevailing assumption has been that cartilage loss is inevitable, a mechanical consequence of lengthening lifespans.

Now scientists are beginning to challenge that assumption. Instead of only cushioning damage or replacing joints, they are exploring whether cartilage can be coaxed to repair itself.

Read the full story: Doctors have long said cartilage can’t regenerate. They’re now rethinking that.

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#88

Doctors have long said cartilage can’t regenerate. They’re now rethinking that.

Nice that doctors have started to catch up.

As I’ve reported this elsewhere in the forum, PEMF worked for me and I’ve got X-rays to prove it;-)

Also… Richard Bedard wrote Saving MY Knees, How I Proved MY Doctors Wrong and Beat Chronic Knee Pain in 2017.

High volume low intensity.

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The book details his recovery from chronic patellofemoral pain syndrome (chondromalacia patella) after doctors and physical therapists failed to help. By researching clinical studies and challenging standard advice (like just focusing on quads), he developed a, successful self-rehabilitation plan.

Key Takeaways and Approach:

  • Challenging Conventional Wisdom: Bedard discovered that the standard advice of focusing only on strengthening the quads, stretching, and taking supplements was ineffective.
  • Research-Driven Recovery: He spent a year researching medical journals and studies to understand cartilage health and joint mechanics.
  • Individualized Plan: He developed a personalized, year-long program that led to a full recovery, proving his prognosis of never getting better wrong.
  • Core Principles: The approach emphasizes informed, active, and patient-driven recovery, sometimes referred to as “informed hope”.
  • Alternative Methods: The book is frequently associated with alternative approaches to knee pain, including strengthening exercises that target the hips and glutes, which help control leg alignment and reduce pressure on the knees
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#89

I’ve had chondromalacia patella since my 20’s. When I was aprox 40, I was told I’d need knee replacements, but because they are best done only once, they wanted me to wait until I was in my 50s.

Fast forward, I met my current PT, and while I will have some knee pain during some of exercises we do, I no longer have any outside of his office. I used to hurt just walking around and living my life. In fact, it was bad enough that I would only buy a house with zero stairs because going down them felt like someone was stabbing my knee with a knife.

So, yes to all you said!

Will you share more about your PEMF? @Alpha

#90

PEMF device for healing injuries and use on the Vagal nerve to affect HRV.

ICES® DigiCeutical® A9 Model System – Flux Health

I’ve posted about this previously.

I had a botched meniscus repair, during which the surgeon made a previously undiscussed decision to shave off irregularities in the cartilage on my right knee. This left me with pain that didn’t go away. Nearly a year later follow up imaging order by my GP showed the surgery had left me with bone-on-bone.

I soon after used the above linked PEMF device every night for a couple of years. Very slowly the pain diminished. Nearly 2 years later further imaging showed regrowth of cartilage.

When a a different orthopedic surgeon review the two sets of images – post surgery and post PEMF – they thought that somehow the dates of the images had gotten switched.

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