iiinova — where your digital self keeps evolving

Jon Brudvig @jonbrudvig.bsky.social · 24/09/2025

Very excited for my next full length Substack post, which will be a deep dive into thymic regeneration, complete with history, risks & benefits, and pharma protocols. In the meantime, here’s a teaser on the topic, shared earlier this year 🧪: #Longevity #Aging

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Jon Brudvig @jonbrudvig.bsky.social · 15/09/2025

In Part 1, we explore: 🧪 Why lysosomes are the forgotten organelle for longevity How longevity interventions are discovered and what this means for their applications in humans. How promising interventions SGLT2 inhibitors are already showing longevity promise in humans.

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Jon Brudvig @jonbrudvig.bsky.social · 15/09/2025

Recently, I sat down with Paul Taylor to discuss the intimate links between lysosomal health and aging. We touched on so many important topics in this one, with an overarching focus on practical, science-backed strategies for living a healthier life. 🧪 #Longevity

podcasts.apple.com

Unpacking Longevity and Cellular Health: A Conversation with Dr. Jon Brudvig - Part One

Podcast Episode · The Paul Taylor Podcast | Expert in Hardiness and Mental Fitness · 05/09/2025 · 41m

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Jon Brudvig @jonbrudvig.bsky.social · 10/09/2025

David is building a fascinating resource: a curated database of personal “longevity stacks” from scientists, physicians, and health optimizers with very diverse backgrounds. 🧪 Check it out at wellstackedlife.com

wellstackedlife.com

Wellstackedlife

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Jon Brudvig @jonbrudvig.bsky.social · 10/09/2025

Last week, I sat down with David Blackmore to walk through my personal #longevity strategy. He did an excellent job distilling our conversation into key takeaways, focusing on diet, exercise, and drugs/supplement approaches. 🧪

wellstackedlife.com

Lysosomes, Wine, and a Real-World Longevity Stack – Wellstackedlife

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Jon Brudvig @jonbrudvig.bsky.social · 27/08/2025

I'm looking forward to joining David and John Gildea tomorrow to record a new episode of the Mara Labs podcast! Stay tuned.

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Jon Brudvig @jonbrudvig.bsky.social · 27/08/2025

David Roberts and Mara Labs just posted a nice, concise article on the #microplastics health problem and #sulforaphane as a potential tool for liberating the particles from cells. 🧪 Definitely worth a read if you are looking for a quick intro. mara-labs.com/blogs/journa... #Longevity

mara-labs.com

Microplastics: A Growing Threat + A Promising Solution

Most people have heard that plastic pollution is choking the oceans. Fewer realize that plastic has also invaded our bodies, even reaching our brains and blood. Startling new research reveals that the...

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

Key sources 2: 🧪 📰 Lithium stabilizes cognitive impairment in AD: pubmed.ncbi.nlm.nih.gov/22746245/ 📰 Mechanistic insights in mice and observational data in humans: www.nature.com/articles/s41...

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

Key sources 1: 🧪 📰 AD incidence with and without APOE4: www.nature.com/articles/s41... 📰 Lithium in drinking water and AD prevalence: jamanetwork.com/journals/jam... pmc.ncbi.nlm.nih.gov/articles/PMC...

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

Observational and interventional studies tell us that microdoses in the range of 0.02–0.3 mg/day are protective. That’s thousands of times lower than psychiatric doses, with a nearly zero risk of toxicity or side effects, and very inexpensive. This is easily achieved with lithium supplements. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

So, why aren't we using it? Experts are hesitating to recommend lithium until optimal doses are confirmed in large, definitive trials. But in high-stakes scenarios like this, waiting for confirmatory evidence could mean missing the window for prevention. Acting now is wise. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

🧠 Mechanisms: blocks tau phosphorylation, shifts amyloid processing, clears plaques. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

💊 Supplementing with 0.3 mg/day slows cognitive decline in Alzheimer's patients. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

🫗 Natural lithium in drinking water → 20%+ reduction in Alzheimer’s rates. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

This is supported by robust observational data from many thousands of individuals, small interventional studies in Alzheimer’s patients, and a relatively robust understanding of mechanism. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 21/08/2025

If you live to 95, your risk of developing dementia is 42%. For APOE4 carriers, it’s as high as 59%. A trace mineral, lithium, can lower that risk at extremely low doses. So potently, that it could even counteract the impact of the worst genetic and environmental risk factors. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 16/08/2025

Huge disappointment is an understatement. We have massive incentives to prioritize the health of ourselves and the planet over economic growth, but again and again we fail to do so. Devastating.

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Jon Brudvig @jonbrudvig.bsky.social · 14/08/2025

Even as evidence builds, many experts hesitate to recommend lithium for Alzheimer’s prevention. That’s a mistake. 🧪 My latest post breaks down the science and gives practical recommendations for implementation. jonbrudvig.substack.com/p/lithium-pr... #Alzheimer's #Longevity #BrainHealth

jonbrudvig.substack.com

Lithium Prevents Alzheimer’s—Here’s How to Use It

Even as evidence builds, most experts hesitate to recommend lithium for Alzheimer’s prevention. That’s a mistake.

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Key Sources 3: 🧪 📰 Metformin blunts exercise adaptations: pmc.ncbi.nlm.nih.gov/articles/PMC... 📰 The case against metformin in healthy individuals: drglorioso.substack.com/p/should-you...

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Key Sources 2: 🧪 📰 Low dose metformin improves healthspan and lifespan in mice: pmc.ncbi.nlm.nih.gov/articles/PMC... 📰 Metformin decreases PD risk only when used at low doses: pmc.ncbi.nlm.nih.gov/articles/PMC... 📰 Metformin blunts exercise adaptations: pubmed.ncbi.nlm.nih.gov/31557380/

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Key Sources: 🧪 📰 Metformin MOA: www.nature.com/articles/s41... 📰 Metformin promotes metabolic health, prevents diabetes, and promotes modest, durable weight loss: pubmed.ncbi.nlm.nih.gov/11832527/ 📰 Metformin reduces systemic inflammation: pubmed.ncbi.nlm.nih.gov/33412927/

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

We don’t yet have RCTs that can confirm the benefits in healthy individuals, and we likely won’t for quite some time. But with current evidence pointing towards benefits across many aging organs, one must also consider the risks of waiting for that evidence to exist.

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

While Peter Attia calls 500 mg a “homeopathic” dose, I disagree. In a healthy individual shooting for gut AMPK activation, a boost in incretin hormones, and mild glycemic benefits, 500 mg ER is plenty. Low doses will also minimize risks from drug effects outside of the gut. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Risks can be mitigated by using a low dose (e.g., 500 mg ER 1x or 2x daily) paired with B12 supplementation, taking periodic breaks, and combining with resistance training to prevent muscle loss. Work with a good longevity doc and stop the drug if you feel worse or see deterioration in biomarkers. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Is it wise to use this drug off-label for longevity purposes? 🧪 My read of the current evidence is a qualified “yes.” In a healthy person that leans towards overnutrition moreso than undernutrition, metformin likely offers systemic benefits and protects against metabolic and inflammatory diseases.

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

What are the key risks? 🧪 🚫 Vitamin B12 deficiency 🧠 Increased risk of Parkinson’s disease in some (not all) observational studies, presumably from brain penetration of higher doses 💪 Potential for blunted adaptive responses from exercise

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

Why might metformin be good for longevity? 🧪 ☑️ Supports metabolic health, prevents diabetes, and promotes modest, durable weight loss ☑️ Decreased inflammation in tissues throughout the body, strongly linked to positive health outcomes ☑️ Extends lifespan (modestly) in animal models at low doses

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

These hormones then exert a range of beneficial effects on target tissues, improving metabolism, increasing satiety, and decreasing inflammation in tissues throughout the body. This is quite similar to #GLP-1 injectables, but occurs in a more coordinated, integrated way. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 13/08/2025

What’s the rationale for and against metformin for #longevity? First, how does it work? As we’ve discussed in recent posts, metformin acts in the gut by binding a lysosomal protein called PEN2 and activating a response that increases production of incretin hormones like GLP-1, GIP, and PYY. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 09/08/2025

Thank you! I’ll check it out.

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Jon Brudvig @jonbrudvig.bsky.social · 07/08/2025

Just realized part of the issue here. Look at the years on the y-axis. The gaps between ticks change from three years before ~2020 to 11 and then 15 years after 2020, which exaggerates the impression of acceleration.

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

And still, there are other examples where the predictions proved to be accurate or even understated. For example, the global rise in CO2 levels and temperatures.

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

Yes, criticised mostly by people with close ties to the plastics industry. There are known limitations with the methodology (some inevitable noise from contaminating lipids), but that does not call the conclusions (trends over time, dementia vs. healthy) into question. It is an excellent paper.

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

In doing so, we can help build support for global treaties aimed at minimizing plastic pollution, and for finding creative solutions that address the health consequences. Please read The Lancet Countdown on Health and Plastics. DM for a copy.🧪 www.thelancet.com/journals/lan...

thelancet.com

The Lancet Countdown on health and plastics

Plastics are a grave, growing, and under-recognised danger to human and planetary health. Plastics cause disease and death from infancy to old age and are responsible for health-related economic losse...

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

What can we, as scientists, healthcare professionals, and humans do about this? We can care enough to spread the word. To educate the public on this very real health concern. To help people understand that this is not a fringe concern, pseudoscience, or internet hype.🧪

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

And this is about to get much, much worse, as plastic production triples from current levels by 2060. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

As plastic production and pollution has increased, levels of microplastics in our brains and bodies have increased in parallel. 🧪 (This figure from another recent paper, in sources at the end)

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

This new report on the health implications from plastics pollution doesn’t mince words. Evidence is piling up that “plastics are a grave, growing, and under-recognised danger to human and planetary health.”🧪

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Jon Brudvig @jonbrudvig.bsky.social · 06/08/2025

This week in the Lancet: “Plastics cause disease and death from infancy to old age and are responsible for health-related economic losses exceeding $1.5 trillion annually.” 🧪 A quick break down and call to action in this thread. #Microplastics #Longevity

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Jon Brudvig @jonbrudvig.bsky.social · 05/08/2025

It was fun to see Felix Harder break down my #microplastics experiments on YouTube 🧪: www.youtube.com/watch?v=JZaJ... I'm working on a follow up post now, with a science update and protocol insights. Stay tuned! Original post on Substack: jonbrudvig.substack.com/p/first-evid...

youtube.com

We Finally Know How To Detox Microplastics From Our Cells

YouTube video by Felix Harder

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Jon Brudvig @jonbrudvig.bsky.social · 29/07/2025

I take that as a major compliment!

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Jon Brudvig @jonbrudvig.bsky.social · 29/07/2025

In other words, metformin isn't just a glucose-lowering drug—it's a top-down rewiring agent for gut nutrient sensing and hormone modulation, which likely underlies the benefits observed across so many organ systems. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 29/07/2025

🧩 Together, these studies reinforce a clear effect on the gut–brain axis: metformin activates AMPK in enteroendocrine cells, restoring their ability to sense nutrient status and secrete hormones that shift metabolism in a positive direction. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 29/07/2025

🧬 Study #2 (Diabetes, July 2025): In high-fat-fed rats, met restored lipid sensing in the upper intestine, triggering release of the gut hormone GIP. • A chronic high-fat diet blocks GIP secretion in response to feeding. Metformin relieves this blockage, restoring nutrient sensing and satiety. 🧪

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Jon Brudvig @jonbrudvig.bsky.social · 29/07/2025

🔬 Study #1 (Lancet eBioMedicine, July 2025): Longitudinal plasma proteomics in ~100 humans before and after met revealed 23 consistently altered proteins. Top hits are signatures of the enteroendocrine cells that produce GLP-1 and GIP, reinforcing that these are the key cellular targets. 🧪

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