Hi Reader,

Surprise! The world's oldest woman had some of the shortest telomeres on record. Meanwhile, researchers just proved your water bottle might be better stress medicine than your meditation app. And Eli Lilly wants you to swallow your GLP-1 instead of injecting it (spoiler: it comes with extra nausea, but worth it?)

The 117-Year-Old Who Broke All The Rules

Maria Branyas Morera died at 117 last summer, but not before diving a major gift to the longevity research community.

The most comprehensive genetic analysis of a supercentenarian ever published dropped this week in Cell Reports Medicine, and it breaks a few of our prior beliefs.

The Telomere Situation Remember how we're all obsessing over (longer) telomere length? Well, Maria had some of the shortest telomeres ever recorded in healthy people.

Some researchers think those stubby telomeres might have actually saved her life by making it nearly impossible for cancer cells to go rogue. Cancer needs long telomeres to replicate endlessly. Short telomeres = cellular retirement plan.

Another explanation: older people simply have shorter telomeres.

Low‑inflammation, efficient lipid metabolism: Maria's NMR metabolomics showed exceptionally favorable lipoprotein profiles—very low VLDL/TG, high HDL with more medium/large particles, larger LDL particles—and low GlycA/GlycB (systemic inflammation markers).

If that sounds like a bunch of gibberish, the main takeaway is she had fantastic lipids and very low inflammation, leading to low risk for heart, brain, and other major diseases.

The Real Magic: Biological vs. Chronological Age While her telomeres were screaming "ancient," her epigenetic clocks were 23+ years younger than her actual age. Her DNA methylation patterns looked like someone in their 90s, not pushing 120.

The Yogurt Theory Maria had one unusual habit - she ate three yogurts, every single day. Her gut microbiome was absolutely loaded with anti-inflammatory Bifidobacterium.

Correlation isn't causation, so I don't think we all will live past 100 with this one trick. But luckily, eating yogurt is at least relatively harmless compared to most longevity supplements.

What You Can Actually Do (backed by Maria's case study and others):

• Eat like you live in the Mediterranean
• Avoid smoking and alcohol
• Move daily (Maria walked an hour per day until 90)
• Manage stress and stay connected to people
• Maybe reconsider that probiotic supplement vs yogurt

The study identified some promising drug targets for immune function and brain health, but don't hold your breath for a longevity pill. We're still years away from translating this into anything you can buy.

💧 Your Water Bottle > Your Therapist?

New research just proved something your mom knew all along: drink more water. But not for the reasons she thought.

Turns out chronic dehydration doesn't just make you thirsty—it basically hijacks your stress response and makes you a cortisol-producing maniac.

The Study That Changes Everything Researchers in the Journal of Applied Physiology tracked 32 people: the well-hydrated (4.4L/day) vs. the chronically parched (1.3L/day - wait...this is me!). Then they stressed them out with standardized tests.

Result? The dehydrated group had 55% higher cortisol spikes. That's not a rounding error—that's your body screaming.

Why This Ruins Your Day (and Your Health) Exaggerated cortisol responses don't just feel terrible—they predict heart disease, metabolic dysfunction, and faster aging. The mechanism involves increase of arginine vasopressin (AVP), which moonlights as both your water regulator and stress hormone DJ.

The Bathroom Test Researchers found that people with dark morning urine (color 4+ on an 8-point scale) consistently showed higher stress reactivity. No blood test, no fancy lab work—just look in the toilet.

If your morning pee looks like iced tea, your stress response is probably broken.

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The Fix

• Aim for pale yellow morning urine (colors 1-3)
• Most adults need 2-2.5L daily minimum
• Track how you feel when properly hydrated vs. when you're running on fumes
• Consider this when your stress levels seem unreasonable

This isn't about becoming a water-chugging influencer. It's about not sabotaging your resilience with something as basic as hydration.

💊 Swallowing Your GLP-1: The Good, Bad, and Nauseous

Eli Lilly just dropped Phase 3 results for orforglipron—basically like an Ozempic you can swallow instead of inject. The results are... interesting.

The Wins:

• 11.2% weight loss at highest dose vs. 2.1% placebo over 72 weeks
• 54.6% of people lost 10%+ of their body weight
• Blood pressure and cholesterol improved
• No more needles (huge win for needle-phobic people)

The "But Wait" Moment: Dropout rates were concerning. 5.3-10.3% quit due to side effects vs. just 2.7% on placebo. The GI side effects seem worse than current injectable GLP-1s, which already make people feel like they have the flu.

How It Stacks Up:

• Semaglutide (Ozempic/Wegovy): ~15% weight loss, weekly shot
• Tirzepatide (Mounjaro/Zepbound): ~20% weight loss, weekly shot
• Orforglipron: ~11% weight loss, daily pill + bonus nausea

The Real Talk An oral option removes the injection barrier, even if the side effects are similar or even slightly worse. I'm predicting FDA approval right around the corner.

Plus, these drugs are showing benefits way beyond weight loss—potential brain protection, heart benefits, maybe even dementia prevention. A daily pill forever, at the right dose to avoid side effects, beats a weekly injection for most.

⚡ This Week's Longevity Speed Round

📱 The $11B Ring Wars​
Oura just raised $875M at an $11B valuation while suing competitors Ultrahuman and RingConn over patents. Ultrahuman is redesigning their entire ring to avoid the lawsuit. Meanwhile, Oura is now hitting $1B in annual sales. 📖

🔍 Plastic's $250B Health Tax​
NYU research reveals childhood plastic exposure costs the US $250 billion annually through hormone disruption and inflammation. Time to rethink that plastic water bottle habit.

🛑 No Agreement in Geneva
​Unfortunately, the Global Plastics Treaty was again not passed given lack of agreement in August 2025's Geneva meeting. This is a major international issue that, unfortunately, we can do very little about without international agreements.

🍫 Inflammation Trends Up with UPFs
​Ultra-processed foods dominate U.S. diets (60% of daily calorie intake) and are linked to elevated hs‑CRP, indicating higher inflammation and increased risk for cardiovascular disease, cancer, and other chronic conditions.

A recent review demonstrated that risk is greatest among older adults, smokers, and those with obesity, showing that the unhealthier you are, the unhealthier you get.

Where You Can Find Me

I've got some cool events coming up where we can geek out about longevity in person:

🔥NYC Longevity Panel – Sept 28, NYC. This is a free panel (tomorrow!) so come join if you can squeeze in past the waitlist!

🎤 Ageless Evolution Summit – Oct 10, Silicon Valley. I'll be speaking First Principles Longevity in Mountain View. Come say hi! Use code DRLIN30 for 30% off your ticket.

⭐ DOC Longevity – Oct 12-14, Napa Valley. I'll be a DOC Fellow this year!

🌐 HLTH USA – Longevity Session – Oct 19–22, Las Vegas. Panel: “Death Becomes Optional.” I'm on stage with the CEO of Nestle Health Science and CSO of Niagen Biosciences. Use code 25HLTH_SPKG_250 for $250 off

Finally, NeuroAgeTx is offering the most comprehensive and science-backed brain aging package to The Longevity Letter readers at up to 61% off (affiliate link here).

Longevity science is getting less about chasing single magic bullets and more about understanding wildly complex, individual patterns.

Maria Branyas breaks our telomere obsession. Hydration research shows how basic physiology trumps fancy interventions. GLP-1 results suggest metabolic health could be managed with a pill a day.

My take: Focus on fundamentals that work for most people (sleep, food, movement, stress, relationships) while staying curious about emerging tools. But don't get seduced by any single biomarker or intervention.

The future isn't one-size-fits-all longevity—it's precision interventions based on your unique biology, psychology, and circumstances.

Hillary Lin, MD

Co-Founder & CEO

​Care Core​

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Follow me for more longevity insights: YouTube | LinkedIn | Instagram | TikTok​

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