🧬 Twenty-One Hundred #1

A weekly dose of evidence-based insights to live a longer, healthier, happier life

Welcome to the first edition of Twenty-One Hundred: a weekly dose of evidence-based insights that help you live a longer, healthier, happier life. 🙌

Thanks for signing up! I hope this newsletter, and all those still to come, extend your life with many years of joy.

The first few editions of this newsletter are going to focus exclusively on simple, easy, scientifically-proven, but above all obvious methods to extend our lifespan and healthspan. Why? Because there are a ton of them out there, most of us already know about them, yet we still fail to take action. I want to change that.

I’ll begin by focusing on the big three: Diet. Exercise. Sleep.

For the first few editions of this newsletter, expect me to experiment with the format and mix up the content as I find my stride. But whatever happens, my goal will always remain the same: help you live to be happy and healthy in the year 2100.

If you’ve chosen to spend your precious time reading this newsletter, please tell me what you thought! Write a comment or DM me on Twitter.

And with that, let’s dive right into this week’s insights. 🫀🤔📚

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1 evidence-based action you can take to a live a longer, happier life

Before I introduce the first evidence-based action you can take to live a longer, happier life, let me describe it. See if you can guess what it is.

  • You don’t need to buy anything. In fact, you’ll save money.

  • You don’t need to go anywhere or do anything outside your usual routine.

  • You don’t need to stop eating any particular foods or stop any specific activity.

Sounds good! But just wait until you hear the benefits:

  • You will lose body fat, especially dangerous visceral fat.

  • Your blood glucose and insulin levels will fall, dramatically reducing the risk of metabolic diseases including heart disease, stroke and type 2 diabetes.

  • You will reduce inflammation, including chronic inflammation.

  • Your bone density and brain neurone development will increase, boosting your cognitive performance.

  • You will reduce your risk of developing cancer.

This sounds like snake-oil bullshit, right? How can there be something so powerful yet so simple? And how can it be free?

The magic I’m talking about is fasting. Specifically, time-restricted feeding, the practice of only eating during a specific 8 hour window each day.

Study after study after study has shown that permanent calorific restriction extends life in humans, in primates, in mice, in yeast — you name it. But nobody wants to go through life being perpetually hungry. So instead, scientists have spent decades investigating the benefits of reducing calories temporarily through fasting.

And there’s good news. Studies found that by restricting how often we eat (intermittent fasting), the benefits were almost as great as restricting how much we eat — even if we consume the same amount of food.

This got famous in the last decade with the 5:2 Diet (500 calories for 2 days per week) or the Every Other Day Diet (500 calories on alternating days). But the problem with those diets are that they’re psychologically very hard — especially in the long-term. Our bodies don’t really adapt to the routine, and so we constantly feel hungry during the fasting periods. Luckily, there’s an easier alternative.

When studies compared intermittent fasting to time-restricted feeding (only eating during a specific 8 hour window each day), they found that time-restricted feeding produces better results than the intermittent fasting diets mentioned above. And while 20% of study participants bailed out of the intermittent fasting regimes, only 10% of study participants couldn’t handle time-restricted feeding. It’s easier on the body and mind.

So I tried it. For the last few months, I’ve only eaten between the hours of 12pm and 8pm. The only thing that passes my lips from the time I wake up until midday is black coffee or water.

For the first few weeks, I hated it. Every single day was an exercise in misery. I realised precisely why nobody seems to adhere to this lifestyle. I spent my mornings hungry, exacerbated by tiredness and longing for my favourite breakfast foods (fruit and fibre cereal with yoghurt, blueberries, and milled flaxseed). It was not fun.

But over time, the hunger pangs disappeared. I forgot about eating until 11am or even later. I no longer felt miserable — in fact, I felt energised.

It turns out there’s a scientific explanation for this, too. Our bodies have a second circadian rhythm which is regulated by the liver, and this can be trained over time just by eating at consistent times of day. Nice! So my body literally no longer expects food in the mornings.

What about performance, mentally and physically?

Since I started skipping breakfast and fasting until midday, I’ve run 4 half marathons on an empty stomach. Each time I consumed nothing but water. Yet somehow my performance didn’t suffer! And I get a lot of my best work done between the hours of 10am and 12pm.

In short: once you adapt to time-restricted feeding, it’s easy. And you get those ridiculous health benefits listed above for free. 🤯 Please enjoy several more years of healthy life courtesy of saving money, being slimmer, and feeling more energised.

Try it. Within 3 weeks of skipping breakfast and fasting until midday, I almost guarantee you’ll be converted. Let me know how it with a comment or on Twitter!


2 challenges and questions to shape your thinking

Stop me if you’ve heard any of this before:

You don’t need to lose any more weight!

Isn’t it bad for your knees to run so far?

I wouldn’t want to put on too much muscle and look all bulky.

Don’t you want any of these donuts?

Aren’t you going to have another beer?

Anyone who ever lost weight, gained muscle, got fit, or improved their diet has faced these kinds of questions and objections. Even the most supportive friends and family members seem to offer up resistance or incredulity when we take positive steps to improve our health and longevity.

These actions will help us live longer, healthier, happier lives! So why do we face resistance?

Sometimes I catch myself reacting in the same way. When I do, I try to examine why I felt so negative. And I think I’ve found the answer.

It all comes back to the cognitive bias known as hyperbolic discounting:

The most important consequence of hyperbolic discounting is that it creates temporary preferences for small rewards that occur sooner over larger, later ones. Individuals using hyperbolic discounting reveal a strong tendency to make choices that are inconsistent over time – they make choices today that their future self would prefer not to have made, despite knowing the same information.

In other words, our brains default to lazy, short-term thinking and neglect the long-term possibilities of self-improvement. As a result, we experience cognitive dissonance — and that uncomfortable feeling makes us react negatively.

Next time someone close to you takes steps to improve their life and longevity:

💪 Challenge yourself: Suppress any negative reaction and offer your full support.

🤔 Ask yourself: How might taking similar steps improve my life and longevity?


3 recommended articles, books, or links

📚 Breakfast is a Dangerous Meal: Why You Should Ditch Your Morning Meal for Health and Wellbeing, by Terence Kealey

Cyclical fasting diets are more effective, both in terms of weight loss and in terms of health, than simple calorie restriction. Of the fasting diets, the 8-hour diet is the best. And of the 8-hour diets, the one that skips breakfast, mid-morning snacks and supper will be the best of all.

Don’t be fooled by the clickbait title. This book was written by a Professor of Clinical Biology, and it’s one of the most informative, well-referenced popular science books I’ve ever read. It’s also my primary source for this week’s recommendation to adopt time-restricted feeding.

Most pop-sci books hide a couple of citations in footnotes or eschew them altogether. Not so here. This book is absolutely packed with citations. More importantly, Professor Kealey spends a huge amount of time discussing the strengths and weaknesses of each study, putting them in context with meta-reviews and later publications, and exposing problematic funding sources. It’s eye-opening, and builds a huge amount of trust for what the author has to say.

🎧 The Peter Attia Drive Podcast #114 – Eileen White, Ph.D.: Autophagy, fasting, and promising new cancer therapies with @PeterAttiaMD

Imagine we had a drug that could cure cancer but we didn’t know how much to give, or when to give it. We wouldn’t tolerate it for a minute. But in fasting, we have one of the most potent tools […] with which we can affect human health but we don’t have a clue how to dose it or with which frequency to use it. I find that ridiculous.

Staying on the topic of fasting: this podcast sees Dr. Peter Attia (Stanford/Hopkins/NIH-trained MD) talk about autophagy, fasting, and cancer with Eileen White, Chief Scientific Officer at the Rutgers Cancer Institute.

Peter’s podcast consistently delivers insights that can’t be readily found anywhere else outside the scientific literature. This episode is well worth a listen because it discusses specific fasting “doses” we can adopt to maximize longevity.

If you only have 10 minutes, listen from 1:13:50 onwards.

Key takeaways:

  • Autophagy (the body's way of cleaning out damaged cells) is triggered by nutrient deficiency. This is why fasting is such a powerful tool for life extension.

  • Exercise, hypoxia, and temperate extremes also strongly induce autophagy, and improve our health and longevity.

  • We don’t know which fasting regimes or frequencies have the optimal effect on our health, or what the minimum effective “dose” might be. For now, the best we can do is perform a water-only fast for 3 days a month and hope it’s enough.

📺 Epigenetic Aging: How old is your DNA? by @foundmyfitness

Rhona Patrick, Ph.D (@foundmyfitness) studies biomedical science and is an expert on nutritional health, the brain, and aging. Her YouTube channel puts out a ton of amazing videos that explain the latest discoveries in the field.

This video is particularly relevant to our goal of living to 2100, because it discusses a state-of-the-art method to identify our actual biological age called GrimAge. Using epigenetic markers, we can understand how old we really are in terms of biological markers rather than clock time. More importantly, we can predict risk of cancer, longevity, and disease risk.

The video also discusses progress towards reducing epigenetic age with the goal of effectively reducing biological age and preventing or even reversing aging itself. Dr. Steve Horvath, the scientist behind the GrimAge clock, thinks that treatments for epigenetic aging may be closer than we think.

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