Nick Norwitz MD PhD Profile picture
Sep 28, 2025 8 tweets 5 min read Read on X
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.Image
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 @AdrianSotoMotaImage
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?Image
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 @MitoPsychoBioImage
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.Image
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.

Premium subscribers get full access for less than 67 cents per letter. Read the full breakdown here → staycuriousmetabolism.substack.com/p/the-oldest-w…Image

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More from @nicknorwitz

Apr 7
Eating 1000 Sardines Gave Me THIS Superpower
(New 2026 Findings!)

1/8) I ran a self-experiment where I ate 1000 sardines in a month.

Sure, it made me stink—but it also gave me one epic superpower. Let me explain. 🧵 (link at the end)

We all know sardines make your breath stink and that they’re nutrient-dense.

That’s basic.

But eating that many sardines changed me. It gave me a “superpower” that had my inner Marvel nerd activated—and my scientist brain scrambling to explain it.

Eventually, I found those data.Image
2/8) It was new paper in a top journal turned confusion into clarity and left me in awe of how much we’re still uncovering about human physiology.

The superpower…

Full deep dive link: staycuriousmetabolism.substack.com/p/why-stinking…Image
3/8) I became cold resistant. The effect wasn’t subtle. I could stand shirtless in a Boston blizzard without so much as a goosebump. Image
Read 8 tweets
Apr 4
Citrus Bergamot for Cardiovascular Health

1/5) One meta-analysis of controlled human trials found that citrus bergamot extract lowers triglycerides, increases HDL, and lowers LDL — to a substantial degree.

But that’s not all... (link at the end) Image
2/5) More interestingly, one trial showed that while bergamot decreased small dense LDL, it increased‘large, fluffy’ LDL.

This shift towards a preponderance of large LDL vs small LDL is a metabolic fingerprint of improved metabolic health. Image
3/5) So how does citrus bergamot work?

Citrus bergamot isn’t a single nutrient — it’s a cocktail of polyphenolic compounds that influence multiple metabolic enzymes.

For example, the bergamot polyphenols inhibit the enzyme ACAT, contributing to downstream increase LDL receptor expression.Image
Read 5 tweets
Mar 31
1/7) Is garlic the new metformin?

A strange new 2026 study suggests compounds in garlic might:
👉Extend lifespan (11.4% in animals)
👉 Improve insulin sensitivity (lower glucose and insulin levels)
👉Reduce fatty liver & reduce inflammation

Let’s break down this bizarre but compelling research.Image
2/7) Garlic is rich in diallyl sulfides (DAS) — sulfur compounds that increase hydrogen sulfide (H₂S) levels. H₂S acts like a hormone: it diffuses through membranes, triggering cellular pathways across the body.

Researchers fed mice a diet enriched with DAS, leading to an 11.4% increase in lifespan, more than double the effect of metformin.Image
3/7) Furthermore, on a glucose tolerance test, DAS-treated mice showed: Lower total glucose and much lower insulin levels

This is evidence of improved insulin sensitivity.Image
Read 7 tweets
Mar 28
How Sleep Deprivation Causally Drives Atherosclerosis

1/5) It’s well established that poor sleep is associated with an increased risk of cardiovascular disease.

But the big question has always been: How… Exactly?

Impressive research published in Nature — one of the world’s top scientific journals — reveals a fascinating biological mechanism. (link at the end)Image
2/5) To test for a causal connection between sleep deprivation and atherosclerosis (the buildup of plaque in arteries), researchers sleep-deprived mice genetically predisposed to developing atherosclerosis.

Compared to well-rested healthy control mice, the sleep-deprived mice developed significantly more atherosclerotic plaque (quantified on the right).

But that’s not all…Image
3/5) The sleep-deprived animals also accumulated more inflammatory immune cells inside their arteries — the very cells that drive plaque formation and instability.

Below you can see a quantification of the immune cells (three types) in the arteries of sleep deprived animals (green) versus healthy controls.Image
Read 5 tweets
Feb 19
1/6) Let’s make this quick, because you don’t have much time…

New research suggests aging isn’t what we thought it was.

It’s not a passive decay process… it’s more like a violent molecular explosion!

Allow me to explain… Image
Image
2/6) The scaffolding beneath your skin, made of collagen, elastin, and other proteins is called the “Extracellular Matrix” (ECM).

Over time, that matrix weakens. But according to new science, aging isn’t just a slow collapse.
It’s a BOOM!

But understanding this BOOM may open a path to stopping it.Image
3/6) When the ECM breaks down — due to aging, injury, or stress — it leaves behind fragments. These aren’t just passive debris.

Many of them act as bioactive signaling molecules known as “matrikines.”
Read 6 tweets
Feb 5
As a Neuroscientist, this Graph changed how I think about Dementia Risk Factors

1/5) Microplastics are accumulating in the human brain at an alarming rate. Over the past ~8 years, brain microplastics have increased by ~50%.

But that’s not the worst part…

Consistently, microplastic levels in the brain are much higher in people with dementia (purple) than in those without dementia.

The association is so massive the graphs needs a Y-axis break!Image
2/5) The researchers behind this work hypothesize that the exponentially increasing concentrations of micro- and nanoplastics in the environment are driving a parallel increase in plastic accumulation in the human brain.

True—correlation ≠ causation. But you cannot do randomized controlled trials here. It’s neither ethical nor feasible.

And when an association is this large—and reverse causality is unlikely—it demands serious attention.Image
3/5) Mechanistically, this makes sense. Microplastics can drive oxidative stress, chronic neuroinflammation, and vascular injury—three core pillars underlying dementia. Image
Read 5 tweets

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