The Longevity Letter #16: He didn't run until 66. At 82, he beats 20-yo athletes.

Juan López García is 82. Retired mechanic. Toledo, Spain.

He didn't run until he was 66.

His VO2 Max was just measured at 52.8 ml/kg/min - the highest ever recorded for someone over 80. The average for his age group? 17.6.

That alone is a remarkable story. But what landed on my desk the same week makes it a better one: the first randomized controlled trial to show that lifestyle intervention can regress epigenetic aging markers. Not slow them. Move them backward.

One is the case study. The other is the mechanism. Together - the strongest argument I've seen that your biological age is negotiable.

In this issue:

• The first RCT showing lifestyle changes can regress epigenetic aging markers

• How an 82-year-old built a 20-year-old's VO2 Max - and my own cardio protocol

• AI outperforms two radiologists, a brain-rejuvenation protein, and Kennedy signals the biggest food policy shift in decades

The First RCT to Show Lifestyle Can Reverse Epigenetic Aging

We've had observational data for years suggesting that exercise, nutrition, and social engagement slow biological aging. But observational data always has the same problem: maybe healthier people just exercise more. Correlation, not causation.

This month, a paper in Aging Cell (Olaso-Gonzalez, Gomez-Cabrera et al., Feb 2026) gave us the trial we've been waiting for. Researchers randomized frail older adults into two groups. One received a coordinated multidomain protocol - structured exercise, nutritional optimization, cognitive training, and social engagement. The other served as controls.

The results went beyond functional improvement. Participants in the intervention group showed measurable regression of epigenetic aging markers. While the scientific community still debates whether true "reversal" of aging is biologically possible, what's not debatable is that the biomarkers clearly moved in the opposite direction of time. The control group's didn't.

Key findings:

• Study design: RCT on frail older adults - exercise, nutrition, cognitive training, social engagement vs. controls
• Result: Intervention group showed measurable regression of epigenetic aging markers
• What moved: DNA methylation patterns - your body's biological odometer - shifted toward a younger profile
• The key: It wasn't just exercise. The combination - especially social connection - may be the most potent lever

This wasn't an isolated finding. A study published the same week in the Journal of the American Geriatrics Society - using data from the Health and Retirement Study - found that social engagement specifically slows epigenetic age acceleration. Social isolation doesn't just feel bad. It measurably accelerates biological aging.

An important caveat: a recent analysis in eBioMedicine (a Lancet journal) argues that epigenetic clocks still fall short of common standards for individual-level clinical utility. Population-level trends are robust, but telling you your precise biological age remains imprecise.

The science is moving fast - and it's moving in the right direction - but we're not yet at "order this test from your doctor" territory.

What we can say: the inputs that shift these clocks at the population level are clear, consistent, and available to you right now.

Your biological age is modifiable. The first RCT to demonstrate this used no drugs - just exercise, nutrition, cognitive training, and social connection.

"Super López": The 82-Year-Old Who Outperforms Athletes Half His Age

If that RCT is the population evidence, Juan López García is the individual case study.

Juan lives in Toledo, Spain. He spent his career as a freelance mechanic, working long hours fixing vehicles to make ends meet. Sport was a luxury he couldn't afford. He didn't run a single mile until he was 66, the year after he retired - when he walked 800 kilometers of the Camino de Santiago in 20 days and one of his daughters told him to try running.

He started slowly. A local group of distance runners in Toledo took him in. His friend Ricardo Ortega - a doctor and running coach - told him his pace put him among the top five in Spain for his age. Juan was surprised. He'd considered himself a complete beginner.

At 70, he entered his first cross-country championship and became champion of Spain. At 75, he went to the World Championships in Torun, Poland, and came back with four gold medals - 3,000m indoor, cross-country, 10K road (42:32, a Spanish record), and half marathon.

In 2025, he set the world record in the 50K ultramarathon: 4 hours, 47 minutes. Just last year, he won gold at the European Marathon with a time of 3:39 - averaging a 5:11 per kilometer pace. At 81.

His nickname in Spain is "Super López." Also: "the Toledo Kenyan."

Researchers at the University of Castilla-La Mancha and the University of Alcalá recently published their analysis of his physiology in Frontiers in Physiology. The headline number: a VO2 Max of 52.8 ml/kg/min - the highest ever recorded for a person over 80.

To put that in perspective:

• The average 80-year-old has a VO2 Max of about 17.6 ml/kg/min. Juan's is three times that.
• The average sedentary American male in their 30s sits around 35-40. Juan, at 82, beats them comfortably.
• NFL football players typically test between 45-55. Juan is in that range - at more than twice their age.
• His value places him at the 80th percentile of 30-year-old men, meaning his aerobic capacity exceeds 80% of men who are 50 years younger.
• For absolute ceiling context: Norwegian cross-country skier Bjørn Dæhlie holds the highest VO2 Max ever recorded at 96. Elite endurance athletes typically hit 70-85. Juan isn't in that tier - but he's in the conversation with professional athletes a fraction of his age.

At 82, Juan's aerobic capacity exceeds 80% of men in their 30s. He didn't start running until 66.

His muscle composition is equally striking: 77% lean mass, comparable to what's expected of U.S. Marines between 20 and 30.

Why does he do it? Partly for the medals. But mainly because his wife Mari has a disability that requires his daily care, and the fitter he stays, the more he can help her.

"We all have problems at home… and when you start running you have the same problems, but they don't look so bad."

As a mechanic, Juan has his own theory about his longevity:

"I perform well now because I didn't wear out the engine when I was young."

The researchers are less poetic but directionally agree: Juan runs 65-120 kilometers per week across six days - roughly 3,500 km per year. That volume isn't realistic for most of us. But we can approximate the training signal using density instead of volume.

A 2018 JAMA study of 122,000+ patients reinforces the broader principle: cardiorespiratory fitness is inversely associated with all-cause mortality with no observed upper limit of benefit. People in the elite fitness category (≥97.7th percentile) had an 80% lower mortality risk than the bottom quartile.

To put that in clinical terms: a bottom-quartile VO2 Max carries a higher hazard ratio than smoking.

My Cardio Protocol (and How to Build Yours)

You don't need Juan's mileage. You need two things: a wide aerobic base and a high ceiling. Zone 2 builds the base. High-intensity intervals raise the ceiling. Skip either one and you're leaving years on the table.

Know your number first. Apple Watch and Garmin estimates are a starting point, but they can be off by ±5 ml/kg/min. I tested this myself - my Apple Watch estimated my VO2 Max at 40, but my formal CPET lab test came in 5 points higher. That delta is the difference between "above average" and "elite" on the age-adjusted charts. The wrist estimate is useful for tracking trends, but don't anchor your training to it without a lab baseline.

A CPET (cardiopulmonary exercise test) gives you the real number. If you're new to high-intensity work, get cleared by your physician first. Start with 2 intervals and build to 4 over a month. This is a decades-long investment, not a 6-week transformation.

The base: Zone 2, 3-4 sessions per week, 45+ minutes

This is the intensity where your mitochondria get their strongest training signal. It's where your body learns to burn fat efficiently, clear lactate, and regulate insulin - effectively an operating system upgrade for your metabolism.

How hard should it feel? You can speak a full sentence, but you'd rather not. "Conversational, but annoyed about it." Roughly 60-70% of max heart rate. Quick shortcut: 180 minus your age gives you a reasonable ceiling.

Why 45 minutes? It takes approximately that long for slow-twitch muscle fibers to sustain the continuous contraction needed to drive mitochondrial biogenesis. Twenty minutes is better than zero. It's just not the same stimulus.

I personally get 150-200 minutes of Zone 2 per week, split across Wednesday, Saturday, and Sunday in 45+ minute sessions. Modality doesn't matter much - cycling, brisk walking on an incline (I use a treadmill at 11% grade, 3 mph), rowing, swimming. Running works but it's harder to stay in Zone 2 as a beginner because your heart rate spikes easily.

One note: a 2025 review in Sports Medicine (Storoschuk et al.) challenged the "Zone 2 is magic" narrative, arguing higher intensities build mitochondria more efficiently per minute. They're correct, technically.

But they're not arguing against Zone 2 - they're arguing against Zone 2 as the only stimulus. The real power is the combination. Zone 2 builds the base; high intensity raises the ceiling. That's polarized training, and it's how virtually every elite endurance athlete structures their week.

The ceiling: high-intensity intervals, 1-2× per week

To move your VO2 Max, you need to signal to your body that its current oxygen delivery system isn't sufficient, forcing adaptation.

My weekly split:

Tuesday - short HIIT: 30-second all-out sprints with rest breaks, repeated twice. This is pure neuromuscular power and anaerobic capacity. Short, sharp, done.

Friday - the Norwegian 4×4: This is the gold standard protocol for VO2 Max development.

• 10-minute warm-up (fast walk or light jog)
• 4 minutes at Zone 5 - breathless, unable to speak a full sentence, 90-95% of max heart rate. You need to be able to sustain this for the full 4 minutes. If you can't, dial it back - slower pace, steeper incline, different modality.
• 3 minutes active recovery (Zone 1-2). Catch your breath, keep moving.
• Repeat 4 times.
• 5-10 minute cool-down.
• Total: roughly 28 minutes.

If running isn't an option - bad knees, joint issues, recovery concerns - do this on an incline treadmill walk (12-15% grade) or a spin bike. Your heart doesn't care how you get the pulse up. It only cares that you do.

Zone 2 builds the infrastructure - more mitochondria, better fat oxidation, improved lactate clearance. The 4×4 forces your heart to its maximal stroke volume, stretching the cardiac muscle to become more elastic and powerful. Together, they are the most evidence-backed exercise prescription in longevity medicine.

The minimum viable dose:

The minimum effective dose: 3× Zone 2 at 45 min + 1× Norwegian 4×4 = about 3 hours per week.

That's the floor for meaningful adaptation. That's the floor for meaningful adaptation. If you can manage 4-5 hours, even better - the mortality data shows no upper limit.

What you should avoid: spending all your cardio time in Zone 3. Too hard to build an aerobic base, too easy to move the VO2 Max needle. That's metabolic no-man's-land, and it's where most gym-goers live without realizing it.

Quick Hits

AI matched two radiologists at mammography - in a 105K-patient RCT

The MASAI trial (Sweden, The Lancet): one radiologist + AI matched or beat dual-radiologist reads. Bonus: the AI also detected breast arterial calcifications - a cardiovascular risk signal. Your mammogram may soon screen for heart disease.

A protein that reactivates aging brain cells

NUS researchers identified DMTF1 as a master regulator of neural stem cell activity (Science Advances). Mechanism: telomere shortening → DMTF1 loss → brain cell decline. Pre-clinical, but specific and plausible.

Kennedy signals the biggest food policy shift in decades

RFK Jr. told CBS' 60 Minutes the FDA "will act on" reclassifying sweeteners - including corn syrup - as no longer GRAS. No regulatory action yet. Watching for rulemaking, not rhetoric.

Social connection as epigenetic medicine

New JAGS data links social engagement to slower epigenetic aging - directly supporting the RCT above. Call a friend this week. Not a platitude - a data-backed intervention.

Until Next Week

Here's the through-line: a randomized trial showed that lifestyle intervention can regress epigenetic aging markers. An 82-year-old mechanic demonstrated that aerobic capacity is far more plastic than we were taught. And three additional papers confirmed that social connection, physical capacity, and biological age are part of the same interconnected system.

None of this requires a prescription.

Open your calendar. Find 3 hours. Start building.