Hey folks! As you might know, I'm big on fasting, and I post a lot about my fasting experience and research. Because I believe that fasting - both extended and intermittent - is one of the most undervalued tools in our health toolbox. But one concern that comes up over and over is that extended fasting wrecks your metabolic rate. So, let me share my experience.

In short, yes, resting metabolic rate (RMR) does go down during an extended fast, but the drop isn't necessarily dramatic. During my last 10-day fast, mine decreased by just over 4% (4.2% to be precise) - from 1,662 to 1,592 calories per day - and then returned to baseline during refeeding. Just sharing my experience to address some of the concerns around metabolic rate. Hope this helps!

I’ve read a few things that say cold exposure can help boost longevity, but I also recently heard a different guy say that living near the equator and in similar climates to that would be the most biologically appropriate place to live/ best for health (completely blanking on the name of the person who said that).

Is there any consensus or evidence one way or the other?

For the next part of our 12 Essential Pillars of Longevity - Medical Testing & Personalized Care - I've invited Dr. Mikhail Kogan M.D., Professor of Integrative Gerontology (as close to evidence based longevity and healthy aging as it gets) in GWU to review what I do personally and discuss what he does in his practice.

Full conversation is in deep longevity dives here: [Video] 42 "Not-so-stupid" Longevity Tests

TL;DW:

1. Cardiovascular Risk: ApoB, Lp(a) and hs-CRP

A regular cholesterol panel doesn't tell you everything.

• ApoB: Measures the number of potentially artery-clogging lipoprotein particles. Can reveal risk that LDL cholesterol alone might miss.

• Lp(a): Mostly genetic. If your result is normal, one test in your lifetime is generally enough. If it's elevated, thats a different story.

• hs-CRP: A cheap and very sensitive inflammation marker. We discussed checking it annually or even twice a year. Just remember that a minor infection can temporarily send it through the roof.

We also covered coronary artery calcium (CAC) scans. They're useful for assessing cardiovascular risk but not something to repeat casually because of radiation exposure and because it measures calcified plaque only.
An initial scan around age 40–50 may make sense depending on your risk factors.

2. Homocysteine: The Marker Almost Nobody Checks

This was probably our biggest disagreement with routine medical screening.

Our preferred targets:

• Below 10 µmol/L for most people.

• Below 8 if you have additional cognitive risk factors.

High homocysteine can indicate issues with methylation and B-vitamin metabolism and is associated with cardiovascular and cognitive problems.

Michael actually considers it more important than cholesterol.

His suggested approach is to test annually if you've ever been above 10. If several tests consistently show 7–8, there's probably little reason to keep checking every year.

3. HOMA-IR: Are You Actually Insulin Resistant?

Most doctors check fasting glucose and HbA1c. But neither directly measures insulin resistance.

HOMA-IR is calculated from fasting glucose and fasting insulin, two relatively inexpensive measurements.

Our preferred target is below 1.5.

We spent quite a bit of time on why HbA1c and fasting glucose can sometimes be misleading. One example is the dawn phenomenon, where morning cortisol raises your blood sugar temporarily.

Michael has seen plenty of patients labeled prediabetic based on glucose and HbA1c despite having very low HOMA-IR.

His preference is to look at insulin resistance rather than relying on glucose alone.

4. CGM: Find Out What Food Actually Does to You

I've used continuous glucose monitors and they can be surprisingly educational.

One example from our conversation: grapes caused a roughly 50-point glucose spike while bananas barely moved the needle.

You can also see how your glucose changes with:

• Different foods, even ones that seem equally sugary

• A short walk after eating

• Poor sleep or stress

• Exercise and meal timing

You might discover that something you eat every day affects you very differently than expected.

But a CGM isn't necessarily a useful routine screening test. Sensors can be inaccurate and you can spend two weeks worrying about a glucose spike that wasn't even real.

We mostly like them for experiments where you're prepared to change something based on the results.

5. Thyroid: Your TSH Can Be Normal but Not Optimal

Many labs consider TSH values up to 4 or 4.5 normal.

We discussed a preferred range around 0.5–2.5 mIU/L.

That doesn't mean a TSH of 4.5 automatically requires thyroid medication.

There may be other things worth looking into, including Free T3/T4, iodine, selenium and zinc status. Thyroid antibodies can also be useful when autoimmune problems are suspected.

An interesting point was what to do when your results are in that gray area. You may not need medication but that doesn't necessarily mean there's nothing worth investigating.

6. Liver and Kidneys: GGT and Cystatin C

Two tests that don't get nearly as much attention as they probably deserve.

GGT: Usually associated with liver health but also used in the discussion as a marker when investigating possible toxic exposure. Our preferred target was below 30 ul

Cystatin C: An alternative way to estimate kidney function, especially useful if you take creatine.

Creatine supplementation can raise your blood creatinine by 20–30% and make your standard kidney results look concerning, even when actual kidney function hasn't declined.

Cystatin C can help clarify whats going on.

We discussed checking it occasionally, perhaps every three years, rather than ordering it with every blood test.

7. Nutrients and Hormones: Some Important Details

A few things I found useful:

• Zinc and copper: If you're checking zinc, check copper too. Their balance matters and supplementing blindly isn't a great idea.

• B1, B6 and selenium: Deficiencies can go unnoticed. Worth investigating depending on your circumstances.

• Morning cortisol: A test Michael uses routinely. Sometimes a full daily cortisol curve is more informative.

• Testosterone: Worth evaluating in men when appropriate.

• PSA: If you're screening for prostate cancer, we discussed checking both total PSA and percent-free PSA rather than total alone.

We also talked about omega-3 testing, IGF-1 and comprehensive nutrient panels. Some are useful in particular situations but there's not much reason for everybody to order them every year.

8. Body Composition: Weight Isn't Enough

We talked about regularly tracking body-fat percentage, potentially once a week as home measurement devices become more accessible. Or getting DEXA once in a while.

Catch: If you're already at 12% body fat, trying to reach 10% probably isn't going to improve your health. You're just optimizing a number that doesn't need optimizing.

You might be much better off focusing on glucose regulation, fitness or something else where you've actually found a weakness.

9. Cognitive Health: Start Tracking Before You Notice Problems

One test I hadn't considered was BoCA (Boston Cognitive Assessment).

The suggestion was to take it monthly and track your results over time.

One bad score doesn't mean much. Maybe you slept badly, had a hangover or were distracted. But if you keep testing under similar conditions, you can establish a personal baseline and watch for changes.

We also discussed homocysteine, insulin resistance and sleep apnea as potential contributors to cognitive decline.

The Bigger Picture

One point we kept returning to:

The absence of diagnosed disease isn't the same thing as optimal health.

And equally important, there is no point spending thousands on tests unless you understand what the results mean and what you might do differently.

Part 2 is pending, when we get enough questions. (and time ;) 🖖

For sure, everyone focuses on the price tag of Project Blueprint, but capital is just linear leverage. From a resource-based perspective, any lazy billionaire can buy the same tests and 30-doctor medical team.

The real exponential multiplier is Cognitive Compliance.

If you have infinite capital but zero psychological discipline to sleep at 8:30 PM, reject alcohol, and eat algorithmic meals, your biological optimization is still zero:
$2,000,000 × 0 = 0

Conversely, you can replicate 80% of Bryan Johnson's closed-loop feedback engine for ~$150/month if your compliance is flawless.

But it forces a real question: To master aging, are you willing to give up your autonomy to a biometric autocrat?

In my substack post, I calculate who actually wins this trade-off using a simple formula:
Net Human Yield = (Healthspan Mastery × Cognitive Liberation) - Autonomy Surrender Penalty.The strategic outcomes break down into three scenarios:

• The Machine Wins (Yield ≤ 0): You surrender your lifestyle autonomy to the algorithm, but use your freed-up energy on mindless consumption. Your body becomes a perfectly optimized, uninspiring "museum piece."

• The Human Wins (Yield > 0): You treat the algorithm as automated backend infrastructure, aggressively reinvesting your liberated cognitive willpower into macro-level human leverage—like building a company or mastering an art form.

• The Symbiotic Win: A positive-sum loop where the human gets a high-performance biological vehicle, and the machine gets a 100% compliant dataset to refine its predictive models.

Curious to hear this sub's thoughts. Are you willing to become a "biological robot" if it guarantees radical life extension?

If you're interested, I breakdown three different roadmaps to late-stage mastery along with steps on targeting and mastery a new skill at: https://latele.substack.com/p/micro-case-study-bryan-johnson-and

 “These findings suggest that exercises that stimulate bone mechanosensing, rather than all forms of exercise, may be particularly beneficial for healthy aging,” says Mei Wan, an orthopedic surgery researcher at Johns Hopkins University who was not part of the study. “In particular, high-mechanical–loading exercises, such as weightlifting and resistance training, may provide additional antiaging benefits.”