The Longevity Letter #2: Why your 40-year-old body betrays you at the gym (solved)

Korean scientists just solved why your workout stops working after 40

Remember bouncing back from everything in your twenties? Korean researchers found the smoking gun.

There's a protein called CLCF1 that surges after exercise in young people but barely budges in older adults. When they gave this protein to old mice, it was like installing a new engine - stronger muscles, denser bones, better mitochondrial function.

The breakthrough? It takes 12+ weeks of consistent exercise for older adults to see the same CLCF1 response that happens immediately in young people.

This completely reframes how we think about exercise prescription. Instead of telling patients "just be consistent," we now know we need to warn them they won't feel the magic for three months. And this opens the door for CLCF1-based therapies - imagine getting the metabolic benefits of a marathon runner's workout from a simple injection.

Immediate Action Items from the CLCF1 Research:

Week 1-4: Focus on consistency over intensity - your body is still “learning”

Week 5-8: Track energy levels, not just performance metrics

Week 9-12: This is when metabolic magic happens - don’t quit at week 10!

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The metformin reality check that wasn't really shocking

A massive meta-analysis of 167 studies from the University of East Anglia and University of Glasgow confirmed what many longevity physicians have been quietly observing.

Rapamycin extends lifespan almost as reliably as caloric restriction across species.

Metformin shows little consistent effect on lifespan when you look at the data objectively.

Many longevity physicians have been noting this pattern in their own reviews. If you're taking metformin purely for longevity (not diabetes), this data might inform your longevity stack.

Side note - I'm still not 100% sold on rapamycin for everyone. Dosing - both dose and timing - remains tricky in humans. On the other hand, I'm not worried about immune suppression concerns at low, intermittent doses. At those levels, it acts more as an immunomodulator than a suppressant. Plus, there's fascinating ongoing research about rapamycin for ovarian preservation that could change everything.

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The brain scan that predicts your death 20 years early

Researchers created an AI that can predict your biological age from a single brain MRI - think of it as a molecular stopwatch for your brain. The fastest agers were 18% more likely to develop chronic disease and 40% more likely to die in following years.

They've filed a patent for DunedinPACNI. This could finally give us surrogate endpoints for anti-aging trials - instead of waiting decades to see if a drug prevents dementia, we could measure "slowing of brain aging" in months.

I'm a big fan of earlier and more regular, even continuous, monitoring in general. We need early warning systems if we're aiming to be healthy for the long run.

What this actually means for your longevity

If you're optimizing yourself - consistency beats intensity, but now we know why. The CLCF1 research proves the magic happens when you do basics reliably for months, not when you chase extreme interventions occasionally.

The hierarchy that still matters:

• Sleep 7-9 hours on a consistent schedule
• Exercise regularly for 12+ weeks to see metabolic changes
• Eat more plants, avoid processed food
• Manage stress and social connections
• Consider evidence-based interventions after these basics are solid

Chemical reprogramming is 8-12 years away. CLCF1 therapies, maybe longer. So we have to stay healthy long enough to benefit from any of this. The most exciting longevity breakthrough means nothing if you're not around to use it.

Do the boring stuff now so you're healthy enough to try the cool stuff later.

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Reply with your biggest longevity question - I personally read and respond to every email, and the best questions become next week's deep dive.

Hillary Lin, MD

Co-Founder & CEO

​Care Core​

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