The Oldest Woman (117) Had “High” Cholesterol 🩸— Here’s What That Really Means🤔(Link 🔗 in 8/8)
1/8) The world’s oldest woman just died. Before she passed, she pleaded, “Please study me.”
A new paper in Cell Reports Medicine (PMID: 39322234) just published provides a deep dive into her genes, metabolism and microbiome. What made this 117-year-old such a supercentenarian?
As a metabolism scientist, this is the kind of data I’d die for (figuratively speaking). Stick with me. I’ll break down what her biology really tells us about aging, and why we might be obsessed with the wrong biomarkers.
2/8) When I first read the paper, I noticed something odd.
The authors detailed her lipid profile (HDL, VLDL-TG, etc.) but her LDL-C and ApoB—the numbers most doctors obsess over—was nowhere in the main text.
I had to go hunting in the supplementary data. There it was, buried in a single line of Supplemental Figure 8B: elevated, and in the “red.” -- Granted, it wasn’t super high… but it wasn’t low either.
So what gives? Why was it not mentioned in the main text. I provide thoughts (not conspiracy theories) in the letter. But now I know I have your attention…
cc @realDaveFeldman @AdrianSotoMota
3/8) Now for the next “paradox” - her telomeres 🧬😲
Telomeres are the protective caps on our chromosomes. Think of them like the plastic tips on a shoelace. The prevailing wisdom is that as they shorten with age, our health declines.
You’d expect a 117-year-old to have either freakishly long telomeres or be riddled with disease. Maria Morera had neither.
Her telomeres were tiny!!! I was expecting Godzilla telomeres and was met with chihuahuas exactly as short as you'd predict for her chronological age.
Yet, she was remarkably healthy. This is a crucial finding: telomere length may simply be a clock, not a direct measure of your healthspan.
cc @bryan_johnson, of interest?
4/8) So if it wasn't long telomeres, what set her apart?
Her mitochondria. As every high schooler knows, these are the “powerhouses in our cells,” and their decline is a key hallmark of aging.
Maria’s, however, were functioning like those of someone decades younger. The paper notes her mitochondria showed "not only preserved but also robust mitochondrial function."
cc @ChrisPalmerMD @MitoPsychoBio
5/8) The evidence for her low "inflammaging" status is compelling. Beyond her genetics, her bloodwork showed remarkably low levels of GlycA and GlycB—advanced biomarkers of systemic inflammation. 🔥
Summary so far: Genetics gave her an edge → leading to highly efficient mitochondria and a low inflammatory burden → which created a biological environment where factors like high LDL or short telomeres didn't lead to disease.
6/8) So, what about her lifestyle? For the last 20 years of her life, she ate a consistent diet that included a conspicuous amount of yogurt—three servings per day.
And the paper even specified the bacterial strains: Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. She was also a heavy user of egg protein and olive oil.
I feel almost as if I designed her diet!
P.S. Smoked Maldon Salt Greek Yogurt is a 12/10
7/8) The clinical implications here are profound. Her case suggests that a state of low inflammation, a “highly engaged lipid metabolism,” and good mitochondrial health can grant resilience against factors we typically view as "bad." Yes, she was genetically gifted. But we can still turn her insights into action… What do we do with this knowledge?
8/8) In the rest of the letter (linked below), we turn these insights into action.
While you can't change your genes, you can support your mitochondria.
I break down her full meal plan, the specific U.S. yogurt brands I found that contain those exact bacterial strains, and actionable strategies — from fasting protocols to light exposure — that support the same mitochondrial resilience seen in this remarkable supercentenarian.
Most Promising Molecules that Fight Alzheimer’s (New Science)
1/12) Here are five molecules that might protect the brain against Alzheimer’s based on new 2025 – 2026 science.
Lock in. This one goes deep!
2/12) The first is lithium.
• Across geographies, higher trace lithium levels in drinking water are associated with lower Alzheimer’s rates.
• Brains with Alzheimer’s disease show lower lithium levels.
• And lithium inhibits a protein (GSK3β) that plays a central role in promoting Alzheimer’s.
3/12) There may even be a vicious cycle.
Research suggests amyloid pathology in Alzheimer’s can sequester lithium, lowering available levels → which may promote more pathology → more sequestration → and downward spiral towards dementia.
1/7) I have astronomically high cholesterol (>700 mg/dl) and high Lp(a) (194), but my arteries are perfectly clear. I mean perfect! 0 mm³ of any measurable plaque upon expert read and AI-guided quantification of my coronary CT angiogram—a finding that left several cardiologists stunned.
2/7) And although I'm young, at levels like mine, this is still stunning. The only historical comparator group are those with a 1-in-1,000,000 genetic condition: homozygous familial hypercholesterolemia (hoFH). Now, I don't have this hoFH. These children typically get severe advanced atherosclerosis and even a heart attack as young as age 8 or 10.
In fact, I have far more lifetime exposure than these children, yet my arteries could not be more perfect.
3/7) I'm not going to chalk up my good cardiovascular health to any supplement one singular aspect of my health routine. Nothing beats being overall metabolically healthy and eating and living well.
Nevertheless, my personal story has inspired a curiosity in readily available natural compounds that can improve heart health. Today's deep dive letter is a result of my obsessive fascination in heart health—a synthesis of tens of thousands of written words and hundreds of papers that I've gobbled up over time.
The Peptide Proven to Cut Visceral Fat (In RCTs) 🧵
1/6) There is a peptide proven in multiple double-blinded, placebo-controlled randomized controlled trials to reduce visceral fat.
It’s called tesamorelin. (link at the end)
2/6) Tesamorelin is an analog of growth hormone–releasing hormone, a hormone released by the brain that signals the pituitary to release growth hormone.
Its main advantage over growth hormone is that it stimulates the body’s natural release of growth hormone, rather than adding a non-physiologic dose that doesn’t align with biological rhythms.
3/6) To give you just a taste of data: in a landmark 2007 New England Journal of Medicine study, patients with HIV on antiretroviral therapy and excess abdominal fat were given 2 mg of tesamorelin or placebo for 26 weeks.
Visceral fat decreased by ~15% in the tesamorelin group, while it increased in the placebo group. Subcutaneous fat did not change, and there was no loss in lean mass.
*Nuance note: Historically, the patient population studied has been patients with HIV taking antiretroviral therapy. Why? These therapies can cause visceral fat gain. So these patients aren’t biologically unique to HIV—they’re just a particularly vulnerable population in which these drugs have been assessed and FDA-approved.
After 7 Years, I Changed My Mind on Cholesterol Meds (Or Did I?)
🚨You'll want to read this one all the way though. Link at the end🚨
1/7) After seven years of living with astronomically high cholesterol, I’ve decided to start two medications. Not statins, but ezetimibe and bempedoic acid.
But that’s NOT the real story. The real story is WHY… and it has nothing to do with cholesterol🤨🤔...
Quick preface: “cholesterol-lowering drugs” are named for one effect, not their full biological impact.
Molecules don’t respect our labels. These drugs can influence multiple systems, including metabolism and brain health.
And in this case, they likely do.
2/7) Take ezetimibe. Beyond lowering LDL, evidence suggests it crosses into the brain and influences neurobiology.
Specifically, is disrupts the interaction between 14-3-3 and hexokinase, reducing protein aggregation.
Full video:
3/7) That means less amyloid, less tau, and even improved autophagy.
Even more interesting: retrospective analyses have found up to an ~8x lower risk of Alzheimer’s in patients on ezetimibe.
Not causal. Not definitive. But a signal worth paying attention to—especially in the right context.
1/5) Here are four things statins do in your body.
First: A human controlled trial found statins reduced GLP-1 levels by 50% in 16 weeks.
The clinical implications aren’t fully clear—but the fact this isn’t discussed is a disservice to science and to patients.
2/5) Statins disrupt mitochondrial function.
They reduce CoQ10 synthesis (a key electron carrier) and directly inhibit Complex IV in the electron transport chain. These are biochemical effects—but they matter for informed decisions. staycuriousmetabolism.substack.com/p/the-mitochon…
3/5) Statins are sexist. Women face higher risk of muscle pain, potential muscle loss, and statin-induced diabetes.