31 May 2025

Nope!

I quite simply refuse to normalize the idea of living in a gangster state. We do, clearly, but this situation cannot be allowed to persist. 

meme


You kinda gotta love this. 


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El pueblo unido jamás será vencido. 
The People united will never be defeated.
DO NOT CAPITULATE! DO NOT BE SILENCED! RESIST!
IMPEACH and REMOVE.

11 May 2025

GKP-1 agonist drugs and cognitive health, as well as other diseases of aging.

I highly recommend to all my older friends (and people who aren't old but want to age healthily) that they read this brief conversation with ChatGPT and start following the exploding research in this area. I have included some links that discuss GLP-1 agonist receptors (like Ozempic) and cognitive health, highlighting very recent and surprising research in this area. 




Here's a somewhat scary point. Seems some of the tech bros, like Elon and Peter Thiel, are early adopters of this pharma science. And they may have induced Trump to take one of these drugs too. I usually am happy for anyone able to improve their health, but it would be ironic if the most damaging and destructive president in our history is enabled to hang on to the bitter end, despite advanced dementia, by drugs created by the very public/private cooperation in scientific research that his regime is trying to destroy. 

09 May 2025

A chat with chat GPT about GLP-1 receptor agonists

This may turn out to be super-important. 

Me:
Please explain how GLP-1 receptor agonists like ozempic work and how they might play an anti-inflammatory role in various "diseases of aging" including cancer, cognitive decline, digestive disorders, overweight, and cardiovascular disease.
ChatGPT said:

GLP-1 receptor agonists like Ozempic (semaglutide) mimic a naturally occurring hormone called glucagon-like peptide-1 (GLP-1), which is secreted in the gut in response to food. These drugs were originally developed to treat Type 2 diabetes, but they have since shown promise in a wide range of conditions—including obesity, cardiovascular disease, cognitive decline, and even cancer—thanks largely to their systemic metabolic and anti-inflammatory effects. Here's how they work and why they may be beneficial across so many domains of aging-related illness:


Mechanism of Action: Basic GLP-1 Physiology

GLP-1 is an incretin hormone produced in the L-cells of the small intestine. It has several roles:

  • Enhances insulin secretion in a glucose-dependent manner

  • Suppresses glucagon release, which reduces hepatic glucose output

  • Slows gastric emptying, prolonging satiety

  • Reduces appetite through central nervous system (CNS) pathways

  • Improves beta-cell function and possibly survival

GLP-1 receptor agonists (GLP-1 RAs) like semaglutide are modified versions of GLP-1 that resist breakdown by the enzyme DPP-4, giving them a longer half-life.


🧠 Anti-Inflammatory and Multi-System Effects

GLP-1 receptors are widely distributed, not only in the pancreas but also in the brain, heart, kidney, vasculature, and immune cells. This broad expression pattern enables GLP-1 RAs to act beyond glucose regulation:


1. Obesity and Metabolic Syndrome

  • Appetite suppression via action on the hypothalamus

  • Improved insulin sensitivity and weight loss, which reduce inflammation

  • Fat loss leads to a decrease in adipose-derived inflammatory cytokines (like IL-6, TNF-α)

  • Lower visceral fat reduces liver steatosis and systemic metabolic strain

These mechanisms help break the vicious cycle of obesity, insulin resistance, and low-grade chronic inflammation.


2. Cardiovascular Disease (CVD)

  • GLP-1 RAs reduce blood pressure, improve endothelial function, and reduce LDL cholesterol modestly

  • Anti-inflammatory effects on vascular walls slow atherosclerosis

  • Multiple large trials (e.g., LEADER, SUSTAIN-6) showed reductions in heart attacks and strokes

  • May also reduce oxidative stress and inflammatory infiltration in vascular tissue


3. Cognitive Decline and Neurodegenerative Disease

  • GLP-1 receptors are expressed in brain regions tied to learning and memory, like the hippocampus

  • Animal models and early trials suggest:

    • Reduced neuroinflammation (glial activation and cytokine expression)

    • Improved synaptic plasticity

    • Increased insulin sensitivity in the brain, which is impaired in Alzheimer's

  • A current trial of semaglutide for Alzheimer's disease (EVOKE) is testing these ideas

Mechanistically, this may relate to decreasing microglial inflammation, reducing amyloid burden, and promoting neurotrophic support.


4. Digestive Disorders

  • By slowing gastric emptying, GLP-1 RAs reduce gastroesophageal reflux and may ease symptoms in gastroparesis

  • Some emerging research suggests beneficial effects in NAFLD/NASH (fatty liver), likely via:

    • Decreased hepatic fat

    • Reduced inflammatory infiltration in the liver

    • Indirect benefits from weight loss and improved glycemic control


5. Cancer (Possible but Controversial)

  • Chronic inflammation is linked to carcinogenesis

  • Weight loss, improved insulin sensitivity, and reduction of systemic inflammation could plausibly lower cancer risk

  • Some lab studies show inhibition of tumor growth (in colon, pancreas, etc.) under GLP-1 RAs

  • BUT: There are also concerns—though not well-substantiated—that long-term use might promote thyroid C-cell tumors (in rodents, not clearly in humans)


⚠️ Why It's Not a Panacea (Yet)

  • Side effects: Common ones include nausea, vomiting, diarrhea; serious ones may include pancreatitis

  • Cost and access: These drugs are expensive, and many insurers (especially Medicare) restrict off-label use

  • Long-term safety data in non-diabetic, non-obese populations is still lacking


Summary

GLP-1 receptor agonists are not just glucose-lowering agents—they appear to be systemic modulators of metabolism and inflammation, with downstream benefits across multiple age-related diseases. Their ability to reduce inflammation, improve metabolic health, and engage receptors in the brain, vasculature, and immune system may account for their broad therapeutic potential.

Would you like a visual chart summarizing their effects across different organ systems?

You said:
yes
ChatGPT said:
GLP-1 Receptor Agonist Effects Across Organ Systems
Output image

Here's a visual summary of how GLP-1 receptor agonists affect various organ systems. Each listed effect contributes to their growing use not only for diabetes but also in addressing chronic inflammation, obesity, cardiovascular disease, and even cognitive decline.   


Jim Long

I am remembering my former partner of over 15 years, and many years after that as family, Jim Long. Today is the anniversary of his death. He was 82. He lived a reasonably long, mostly healthy, and meaningful life. We shared many special connections and Brad and I both miss him terribly. The past year has been difficult, especially the first few months. I am not religious, but I share his belief that there is something transcendent. If some essence of him is out there among the stars, I say, good venture, love, old friend. 

08 May 2025

Pearls Before Swine

Recent entry for my favorite comic of the year

07 May 2025

New Musical "Antichrist"

OMG. A friend sent this link. 

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.............
El pueblo unido jamás será vencido. 
The People united will never be defeated.
DO NOT CAPITULATE! DO NOT BE SILENCED! RESIST!
IMPEACH and REMOVE.