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.
🚨The New Dietary Guidelines Are Internally Inconsistent
1/7) Publicly, RFK Jr. says “we’re ending the war on saturated fat.” The iconic food pyramid has been flipped, with butter and beef now at the top.
But read the actual guidelines, and you’ll find the exact same restriction: saturated fat still capped at 10% of daily calories. No change.
(People may not like this thread or the linked long-form letter. But I'm not here to pander or choose political sides. I'm here to seek the clarifications I know Americans want and to 'tough love' this step in the right direction into a proper leap...)
cc @RobertKennedyJr @HHSGov
2/7) How can one recommend:
👉Cooking with butter and tallow
👉Eating full-fat dairy three times a day
👉Prioritizing red meat…
🚨Yet still limit saturated fat to 10% of calories? That’s not an opinion. The math doesn’t math?!
1/10) No word yet from 'Dr' Johnson. So, I've decided to use this as a springboard to deeper learning.
Quick review: in a recent Twitter exchange between @chamath and @bryan_johnson, Bryan proclaimed: “Definitely do not stop statins.”
Today, we deconstruct common logical missteps that could lead to this misguided medical mandate.
A 🔗 to the full letter is at the end.
This won't be shallow reaction content, but an opportunity to dive deep...
2/10) Main Point #1: Causality is Overrated
Just because a molecule or biomarker plays a causal role in a disease process does not mean it is sufficient to cause disease.
More importantly, it does not mean intervention is the prudent path.
The presence of a “causal” variable does not ensure disease nor is the treatment benign.
3/10) Let me emphasize the point with an intentionally absurd analogy.
A penis is part of the causal pathway by which a biological male contracts a sexually transmitted disease. Amputation of the causal variable will reduce STD risk.
But in this case, as with the case of LDL cholesterol, presence of the causal variable does not ensure disease nor is the treatment benign.
1/6) The bile acid and supplement, TUDCA, has the potential to reduce atherosclerosis.
And it appears to do so not by lowering cholesterol, but by reducing inflammation inside arteries. (Red = fatty deposits in arteries)...🔗 in 6/6
2/6) In atherosclerosis, macrophages in the artery wall take up too much oxidized LDL.
This can trigger *ER stress* and activate inflammation, pushing the macrophages into *foam cells* that are a cause and hallmark of atherosclerosis.
3/6) In TUDCA supplementation experiments, TUDCA did not alter total cholesterol or LDL cholesterol levels but led to a significant reduction in arterial fatty deposits in arteries (red staining).
5 Things to Know About Cholesterol-Lowering Drugs 🧵
1/6) Statins are the go-to prescription — but with baggage.
They can:
👉Deplete GLP-1
👉Cause insulin resistance
👉Trigger muscle pain/damage and potentially muscle loss
These risks aren’t often mentioned, but they should be part of a real cost-benefit analysis.
🔗 to the letter at the end, including all hyperlinked references
2/6) Lp(a) and Drug Effects
👉PCSK9 inhibitors = tend to lower Lp(a)
👉Statins = tend to raise Lp(a)
This often-overlooked detail could matter a lot depending on your individual risk profile.
3/6) Ezetimibe blocks cholesterol absorption in the gut — both dietary and recirculated. Liver compensates by increasing LDL receptors.
Its effects are usually modest compared to statins and PCSK9 inhibitors, but if you're low-carb/high-fat you’re naturally recirculating more cholesterol + bile.
Thus, if you’re low-carb, ezetimibe becomes a much more powerful tool for ApoB and LDL lowering.
Creatine Explained: How One Molecule Boosts Muscle and Brain Health 💪🧠🧵
1/11) Creatine is one of the most extensively studied performance-enhancing supplements in the world of exercise science and nutrition.
And yet, despite its popularity, few people truly understand how it works or what its full range of effects might be.
So, let’s break down what you need to know about creatine.
💪Muscle Hypertrophy Mechanisms
💪Brain Health
💪Protocols
2/11) There are several mechanisms through which it can support muscle growth (a.k.a. hypertrophy):
First, Satellite Cell Activation
When muscle fibers grow, they require additional nuclei to manage the increased protein production.
Unlike most cells, which contain only one nucleus, muscle cells are multinucleated. These extra nuclei come from satellite cells—a type of muscle stem cell.
Combined with resistance training, creatine stimulates satellite cell activity, which helps supply growing muscle fibers with the extra nuclei they need to expand.
In simpler terms: creatine makes it easier for your muscles to grow by helping recruit and integrate new cellular “command centers” (nuclei) into the muscle fibers.
3/11) ii. Cell Volumization: Creatine draws water into muscle cells, increasing intracellular hydration.
This “cell swelling” is more than just cosmetic—it acts as a signal that stimulates protein synthesis.
Over time, this contributes to an increase in muscle mass.