This week's Genetic Lifehacks newsletter is out. In it, I'm covering the new work on PANS/PANDAS that keeps pointing at IL-17. In a mouse model of PANDAS, repeated strep infections set off a Th17 response that reached the brain through the olfactory bulb. There, IL-17 acted on microglia and made the blood-brain barrier leakier. Human data fits the picture. Kids with PANS/PANDAS have shown elevated IL-17 in blood and CSF, with the spinal fluid signal looking stronger. IL-17 is also the cytokine that helps defend skin, gut, and lung barriers against strep, Candida, and other pathogens. So the research caution matters. Blocking it during an active infection could backfire. The interesting question is whether targeting the receptor after the infection settles could help. Full newsletter (with diet/supplement angles for high IL-17) geneticlifehacks.substack.co…

Melatonin isn’t only a sleep pill. Levels fall with age as the pineal gland changes and calcifies. Animal studies links supplemental melatonin to longer survival in some models, better mitochondrial function, and immune effects. One diabetes-linked melatonin receptor variant (MTNR1B) even interacts with when you eat dinner and diabetes risk. Sleeping in the dark, blocking blue light in the evening, and getting bright morning light still do more for most people than a melatonin gummy. Find out more - geneticlifehacks.com/melaton…

Slow COMT here, this is helpful info 👇

When an older heart is transplanted into a younger person, it doesn't stay "old." Vadim Gladyshev's lab shows the heart actually starts aging on the timeline of the body it's now living in — its biological age shifts to match the recipient, not the original donor, at the molecular level. biorxiv.org/content/10.64898…

This is an interesting new study on PANDAS - group A strep infections that cause BBB dysfunction and affect the basal ganglia. pmc.ncbi.nlm.nih.gov/article… I’m updating my IL-17 article with this information: geneticlifehacks.com/chronic…

I also write at Longevity Lifehacks for people building a longevity stack who want the “why” behind each bottle/supplement. Here’s an example: NAD+ can fall by about 50% by midlife, partly because inflammatory CD38 burns through it. Pairing NMN/NR with a CD38-leaning flavonoid may be better than either one alone. longevitylifehacks.substack.…

COMT clears dopamine, norepinephrine, and some estrogen metabolites. The common Val158Met variant changes the amount of available enzyme. Slow COMT can mean better working memory and more stress sensitivity. Fast COMT often flips that, and it is sometimes called the warrior gene (dumb name). Slow COMT + a sudden influx of methyl donors (e.g. methylfolate, methyl-B12, SAMe, TMG) can feel like mood whiplash - irritability, anxiety, irrational anger. Quercetin/luteolin can inhibit COMT. Check your genes to know (or ask your spouse AITA...) geneticlifehacks.com/comt-ge…

PANS/PANDAS mechanism just published: (They studied strep but it's not limited to strep, I've seen many cases from bartonella) Strep → IL-17A → microglia → leaky blood-brain barrier → sudden personality changes, OCD, tics, & many more. For 20 years parents were told it was psychosocial. It was inflammation due to an infection. It always was.

A Mayo Clinic team just built the cleanest causal test I've seen for NAD's role in aging. They engineered mice whose NAD synthesis depends entirely on dietary niacin, then pulled the niacin. Result: kyphosis, muscle and bone loss, cataracts, frailty, cellular senescence, shortened lifespan. Put niacin back and most of it reverses, without fully restoring NAD. That partial-restoration gap matters. It says NAD depletion triggers senescence programs that do not simply snap back when the cofactor returns. We flagged senescence as a load-bearing hallmark in the Biomarkers of Aging Consortium work (Moqri et al., Cell 2023); this is a rare in vivo model that makes the causal chain from cofactor to senescence to phenotype explicit and reversible. Nat Commun, Benitez-Rosendo, Chini et al. doi.org/10.1038/s41467-026-7…

The blood-brain barrier isn’t just about Alzheimer's. An MRI study in long Covid patients with cognitive symptoms showed BBB leakiness years later. Systemic inflammation plus local barrier failure shows up as a pattern in brain fog research in general. Claudin-5 (CLDN5) holds tight junctions together, but stress and inflammatory cytokines can decrease CLDN5. APOE4 also ties in via MMP9 and barrier wear. Supporting the barrier (decreasing inflammation, sufficient DHA/EPA, metabolic control) is good for everyone. geneticlifehacks.com/blood-b…

Today I met a new patient. She has been treated for Crohn's disease since 1996 without any remission. For the last two years, she has been on Glp-1, and she is in remission, Completely symptom-free. Is it due to reducing pro-inflammatory cytokines, supporting epithelial barrier function, and promoting mucosal repair from Glp-1? We need more research on GLP-1s and their effects on inflammatory bowel disease. #Crohns #Glp1 @BeckyQuick @ScottGottliebMD

Diet soda isn’t always the right move for everyone. In a large cohort, >2 L/week of artificially sweetened drinks tracked with about 20% higher AFib risk (sugar-sweetened drinks raised risk ~10%). Importantly, people already at higher genetic risk for AFib saw a much steeper increase in risk. Separate research found ~30 days of sucralose linked to ~20% lower insulin sensitivity in lean adults, with gut microbiome shifts. To be clear - the risk from diet drinks isn't huge or acute. But it may be worth weighing if AFib, stroke family history, or insulin resistance is already on your radar. geneticlifehacks.com/artific…

Waking at 3 or 4 a.m. and staring at the ceiling isn’t always just “stress.” Or cortisol. Histamine naturally peaks in the early morning (average around 5:30 a.m.) as part of the wake-up system. When circadian rhythm is off, or inflammation is increasing histamine from mast cells, that peak can overshoot. Melatonin normally helps quiet mast cells. Blue light at night decreases melatonin. And allergens in the bedroom (pets, dust, etc) increase histamine. Genetics plays a role in susceptibility - DAO/HNMT variants change how well you clear histamine. To be clear - Not every early waking problem is due to histamine levels rising too earl. However, for some people decreasing histamine (low-histamine diet, DAO supplements) is the exact right thing for sleeping through the early morning hours. geneticlifehacks.com/histami…

Wow! multiple sclerosis is caused by viral reactivation in monocytes and B cells months before clinical onset. nature.com/articles/s41591-0…

GLP-1 drugs get all the headlines for weight loss - and for the contrarian view points. The real question is why so many people seem to need that signal boosted in the first place. There are several environmental and lifestyle things that show up in the research as dampening natural GLP-1. Glyphosate can shift the gut microbiome in ways that reduce GLP-1 production (mouse study, but using realistic exposure levels). Statins have a similar microbiome story in some data. Circadian disruption (blue light at night, screens) also lowers GLP-1. If baseline GLP-1 is getting nudged down by glyphosate, blue light at night, and even some medications -- well, it makes sense and tracks with the obesity epidemic. geneticlifehacks.com/glp-1-a…

Waking at 3 or 4 a.m. and staring at the ceiling isn’t always just “stress.” Or cortisol. Histamine naturally peaks in the early morning (average around 5:30 a.m.) as part of the wake-up system. When circadian rhythm is off, or inflammation is increasing histamine from mast cells, that peak can overshoot. Melatonin normally helps quiet mast cells. Blue light at night decreases melatonin.  And allergens in the bedroom (pets, dust, etc) increase histamine. Genetics plays a role in susceptibility -  DAO/HNMT variants change how well you clear histamine. To be clear - Not every early waking problem is due to histamine levels rising too earl. However, for some people decreasing histamine (low-histamine diet, DAO supplements) is the exact right thing for sleeping through the early morning hours. geneticlifehacks.com/histami…

Would never have thought that defining the brain as two organs would have implications like “…for creating ethical brainless clones for transplant.”