Ground Truths

Yo-El Ju is the Barbara Burton and Reuben Morris Professor of Neurology at Washington University, St. Louis. She got her AB from Harvard and MD from Columbia and actively practices sleep medicine and is a prolific researcher, one of the top sleep scientists in the country.
Here are some of the topics we discussed and a few related hyperlinked citations:
—Importance of Deep Sleep (and her paper on what happens when deep sleep is purposely disrupted, how it is modulated, effect of alcohol
—The Orexin Antagonist drugs that promote sleep (and a study that shows they can reduce p-tau217 and other neuroinflammation markers
—Link of sleep regularity with less all-cause, cardiovascular, and cancer related mortality
Figure 3.9 from SUPER AGERS (SRI-sleep regularity index)
More things we discussed:
—A sleep foundation model that predicts 130 diseases
—Impact of menopause on sleep
—Getting to sleep vs staying asleep
—Role of naps
—Impact of interruptions of sleep
—Sleep apnea and new interventions
—Vagal nerve stimulation and sleep
—Cerebrospinal fluid wave that occurs during attention lapse after poor sleep
—cognitive behavioral therapy for improved sleep
—Wearables, sleep scores, and effect on sleep
—Any supplements that help sleep?
—The rare genetically endowed short sleepers

Thank you Jeoffry Gordon, MD, MPH, Dr. Sara Wolfson, Lynn L, Vau Geha, Bernie Newman, and more than 600 others for tuning into my live video with Yo-El Ju! Join me for my next live video in the app.
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Thanks to Ground Truths subscribers (> 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
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I also want to thank the National Academies of Science, Medicine and Engineering for their recent recognition.



Get full access to Ground Truths at erictopol.substack.com/subscribe

Get full access to Ground Truths at erictopol.substack.com/subscribe

The vagus nerve, also known as the Great Nerve, connects the brain to all parts of the body, like an internet (Figure below). Every week we’re learning more about its importance for health and disease. Until recent years the brain and immune system were thought to be in separate “firewalled” compartments. But that turned out to be far from the truth.

Dr. Kevin Tracey, who directs the Feinstein Institute at Northwell Health, has been studying the vagus nerve for more than 3 decades. In the early 1990’s he made the seminal observation that stimulating the vagus reduces the inflammatory cytokine known as tumor necrosis factor (TNF), what he described at the time as a “holy s**t” moment. In 2025 he published the book THE GREAT NERVE with many rich patient anecdotes and the history for how this field developed.
I wrote about the brain-immune axis previously on Ground Truths, spotlighting the vagus nerve’s role. That included much more on depth of the pathways if you are interested.
We discussed the recent FDA July approval for refractory rheumatoid arthritis (RA)(unresponsive to medications or intolerance to medical therapy) based on a sham-controlled randomized trial published in December 2025 in Nature Medicine. It is striking that the benefits were derived from 1 minute of vagal stimulation per day. That stimulation is barely perceived (tingling, many not at all) by device recipients. The surgery takes one hour to implant the tiny stimulator device along side the vagus nerve in the neck.
But this is much bigger than a treatment for RA. It is now being tested for lupus, Crohn’s disease, and other autoimmune conditions. That’s beyond the role vagus nerve stimulation (VNS) has played for epilepsy and depression, independent of VNS’s anti-inflammatory impact (Tracey named it “the inflammatory reflex”).
We also discussed handheld VNS devices, potential use for Long Covid and POTS, cold plunges, heart rate variability, stress, and other topics related to the vagus nerve and parasympathetic nervous system (the brakes, “rest and digest” as opposed to the sympathetic nervous system (the gas, “fight or flight”).
Most people are not aware of this device approved treatment for an autoimmune disease. Our treatments are so drug-centric but they are immunosuppressive, have important side-effects, and are expensive. It’s good to see a non-drug approach get compelling data as an alternative. Moreover, as I recently wrote about, there’s a shift ongoing from treatment to cures vs autoimmune diseases that will be adding to the mix.

Here are some very recent papers about the vagus nerve to give you a sense about how its prominence is getting appreciated more all the time
Gut-brain-vagus axis for reward circuit and addiction, 30 Jan 2026, Science Advances
Randomized trial of VNS for depression , Int J of Neuropsychopharm 2026
The vagus nerve role in heart function after a heart attack, Cell, February 2026
Vagus receptors and hemorrhage, blood volume, Nature, 28 Jan 2026

A Quick Poll

Thank you Harshi Peiris, Ph.D., Tay MacIntyre, David Dansereau, MSPT, Max Manwaring-Mueller, RJ, and over 600 others for tuning into my live video with Kevin J. Tracey, MD! Join me for my next live video with Robert Wachter Feb 4th, 12:30 PM PT in the app.
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Thanks to Ground Truths subscribers (approaching 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.


Get full access to Ground Truths at erictopol.substack.com/subscribe

Back in 2005 Dan Buettner patented Blue Zones. He’s written 9 books, of which 5 were NY Times bestsellers, and has another one in the works. His 2023 Netflix documentary series “Live to 100: Secrets of the Blue Zones” won Emmy awards and was widely viewed. Many of the main points that Dan has emphasized over the years—healthy diet (he highlighted whole grains, beans, nuts, greens, and “peasant food” here), physical activity, social engagement, and sense of purpose—are backed up by randomized trials and/or large, prospective studies, as I reviewed in Super Agers.
In this interview, I asked Dan about the critique he’s faced, predominantly from Saul Newman, a biologist in the UK, about accuracy of the data for extreme longevity in the blue zones. In December 2025, two of his collaborators published in The Gerontologist a rebuttal response (open-access) entitled “The validity of Blue Zones demography: a response to critiques” on the rigorous demographic work they’ve done.
We also discussed the marketing and business operations of Blue Zones LLC, the company he sold to Adventist Health in 2020. His son, Danny, is the EVP of the company and likely successor to Dan’s work in the future. As Dan said, “He’s my genetic upgrade.”
I hope you find this conversation informative. An AI-generated transcript is available in the tab at top right above.
Some biomedical updates from the past week:
* A vaccine to prevent colon cancer in carriers of mutations of Lynch Syndrome looks good for strong immune response and safety, ready for Phase 3 clinical trials
* A review of the data of Tylenol during pregnancy reaffirms its safety and lack of increased risk for autism, ADHD, and intellectual disability.
* Our perspective/review on how AI and large language models can reduce global health inequities
* Another big jump vs refractory autoimmune diseases, this time for hemolytic anemia, using engineered T cells. See my recent review of this topic, from treatment to cures.
* A pair of new large prospective cohort studies that reinforce the importance of even small increases in physical activity, along with sleep and diet, for reduction all-cause mortality and improvement in healthspan.

Thanks to Ground Truths subscribers (nearly 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026

Thank you Annie Fenn, MD, Harshi Peiris, Ph.D., Strategy Shots, Rebecca Moore, Lynn L, and many others for tuning into my live video with Dan Buettner! Join me for my next live video in the app.


Get full access to Ground Truths at erictopol.substack.com/subscribe

Jonathan Kipnis is a neuroscientist, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at Washington University, St. Louis, who discovered meningeal lymphatics and has been a prolific researcher in brain drainage and the continuous immune system surveillance of the brain.
I made this infographic with the help of Notebook LM to summarize many of the concepts we discussed. (Notebook LM is free and worth trying)

We went over his new review with 24 co-author leading experts in the recent issue of Neuron
A Clever Cover
The drainage system anatomy on influx and efflux (blue arrows)
The 3 ways the flow of glymphatics are modulated. I mentioned the recent studies that show atrial fibrillation, via reduced cardiac pulsation, has an effect on reducing glymphatic flow.

We also discussed his recent review on the immune surveillance system in Cell:
A schematic of key channels for the “faucet” and “drain”
and how the system changes from healthy to central nervous system autoimmune diseases (such as multiple sclerosis) and aging with different immune bar codes.
The outsized role of astrocytes in the brain, a subject of recent Nature feature, was also mentioned.

Our understanding of the brain’s immune system has been completely revamped. Kipnis’s recent review in Nature Immunology highlights the critical role of the outer layers —the skull, dura and meninges—as an immune reservoir that is ready to detect and react abnormalities in the brain with a continuous “intelligence report.”
Notably, Kipnis touched on lymphatic-venous anastomosis (LVA) surgery (Figure below) for Alzheimer’s disease which is popular in China, available at 30 centers in multiple cities, and the subject of multiple randomized trials as a treatment for Alzheimer’s. Trials of LVA surgery are also getting started in the United States for treatment of Alzheimer’s and Parkinson’s diseases.
Here is a Figure to show the surgical anastomoses (connections) from the deep cervical lymphatics to external jugular and internal jugular veins
This podcast was packed with insights relevant to health, spanning sleep quality, sleep medications, autoimmune diseases, and Alzheimer’s disease. I hope you find it as informative and engaging as I did.
A Poll
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This is my 4-year anniversary of writing Ground Truths. Post number 250! That’s an average of more than 1 per week, nearly 5 per month. Hard for me to believe.
Thanks to Ground Truths subscribers (approaching 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!

If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026

Thank you EG, Alan, Lynn L, Stacy Mattison, Jackie, and many others for tuning into my live video with Jonathan Kipnis! Join me for my next live video in the app.


Get full access to Ground Truths at erictopol.substack.com/subscribe