“There are only two ways to live your life. One is as though nothing is a miracle. The other is as though everything is a miracle.” 

- Albert Einstein

“The virtue of a person is measured not by his outstanding efforts, but by his everyday behavior.”

- Blaise Pascal

“It is never too late to be what you might have been.” 

- George Eliot

A. The Science of Ageing

I recently re-read David Sinclair’s book Lifespan.

Aging is something I have been geeking out on for a while and David’s book is one of the best. Another good one is Juvenescence by Jim Mellon and a more practical one is How Not To Die by Dr. Michael Greger.

One amazing statistic on longevity by the way: our bodies are in a state of continuous regeneration. On an annual basis, 95-98% of our bodies are completely new. 

And one of the great charts:

What it means is that:

It turns out that the United States spends hundreds of billions of dollars each year fighting cardiovascular disease. But if we could stop all cardiovascular disease - every single case, all at once - we wouldn’t add many years to the average lifespan; the gain would be just 1.5 years. The same is true for cancer; stopping all forms of that scourge would give us just 2.1 more years of life on average, because all other causes of death still increase exponentially. We’re still aging, after all.

Aging in it’s final stages is like a fast sprint over an ever-higher and ever-closer set of hurdles. One of the hurdles will eventually send you for a tumble. Take away one hurdle, and the path forward is really no less precarious. That’s why the current solutions, which are focused on curing individual diseases, are both very expensive and very ineffective when it comes to making big advance in prolonging our healthspans. What we need are medicines that knock down all the hurdles.

David’s thesis combines the latest in genetics and epigenetic work with Claude Shannon’s original Information Theory (that the internet is built on top of) to arrive at the Information Theory of Aging.

To simplify something complex into a few sentences, here’s how it goes: We all start with our cells having ‘perfect’ information. Over time, you can think of the data in your cells being like a CD that has gotten scratched or covered in dust (a process called methylation). 

At this point the information or instructions that was meant to be conveyed to your cells is corrupted, which leads to small mistakes, noise, differences between what the CD had on it versus then data being read. This leads to entropy and incorrect expression of genetic data.

But, we are now finding processes by which we can go clean up that CD, to wipe away the dust and return it back to it’s original state. So the instructions look like when you were younger. 

They have already been able to reverse ageing and restore blindness in mice. 

Key terms to know:

Horvath clock - your body’s epigenetic clock

Yamanaka factors - ability to take our cells to their original pluripotent stem cell state.

Great 18-min talk:

One of the best resources I found was a podcast with Peter Attia and David Sinclair - it’s a bit heavy on the science.

In terms of just simple stuff to do if you’d like to live longer, if you don’t want to take supplements like Resveratrol, Rapamycin, NAD+ boosters or Metformin (I have tried the last two), and are already eating well and sleeping well (and not smoking or drinking much), then you can try intermittent fasting and some amount of caloric restriction. 

Here are the big ones to extend / maximize your life:

No. 1: SLEEP: Sleep is when the brain turns on a ‘washing machine’ type mechanism, where the fluid that bathes the brain is washed away and replaced. Sleep is also when short-term memory (things you learned that day) are converted into long-term crystallized memory. Poor sleep is one of the major risk factors for ALL age-related diseases, particularly Alzheimer’s and dementia!

Make sure you get eight hours ideally. If you have trouble sleeping, highly recommend you read Matthew Walker’s Book: Why We Sleep or check out podcast notes here.

No. 2: DIET: Sugar is the worst. Ideally NO sugar at all. Ideally NO “cheap” carbs like pasta, rice, bread. There is low micronutrient value to these ‘filler’ foods. Most people require some carbs, so focus on low-glycemic index carbs such as lentils/beans (well cooked, if you are not sensitive to plant lectins), tubers, vegetables, and oats. Minimize very sugary, high glycemic index fruits such as bananas or melons. If you must eat something sweet, eat it at the end of your meal, after a salad. The rate of absorption will be slower. 

Best diet: High unsaturated fats, low glycemic index carbs, less than 20% calories from protein.

Definitely try intermittent fasting or calorie restriction of some kind.

No. 3: EXERCISE: Good mix of high intensity interval training (HIIT), weight training and stretching is best. Make time for 60-90 mins of physical activity daily - even a brisk walk helps.

No. 4: STATE OF MIND: Preserve and maintain a positive mindset, practice yoga, mindfulness, meditation. Have purpose and love in your life.

No. 5: SUPPLEMENTS: A handful key supplements do help, but focus on No. 1-4 before you take any supplements. I take Metformin, NR, Magnesium Citrate, Vitamin B12 and D. Note: Please consult your healthcare professional, I’m not a doctor and don’t intend to play one on the internet.

Key books to read on longevity and extending a healthy lifespan:

How Not To Die - Dr Michael Greger

Lifespan - David Sinclair

Juvenescence - Al Chalabi and Jim Mellon

Borrowed Time: The Science of How and Why We Age - Sue Armstrong

Regenesis - George Church

The Immortal Cell - Michael West

Transcend: 9 Steps to Living Well Forever - Ray Kurzweil and Terry Grossman

What’s your plan for living longer?

B. The Fourth Turning

The Fourth Turning by William Strauss and Neil Howe, is turning out to be a very prophetic book. We had discussed it previously in May.

The authors wrote in 1997:

“The next Fourth Turning is due to begin shortly after the new millennium, midway through the Oh-Oh decade. Around the year 2005, a sudden spark will catalyze a Crisis mood. Remnants of the old social order will disintegrate. Political and economic trust will implode. Real hardship will beset the land, with severe distress that could involve questions of class, race, nation, and empire.”

The Fourth Turning is due to continue as the great unraveling runs its course until about 2027.

“Sometime before the year 2025, America will pass through a great gate in history, commensurate with the American Revolution, Civil War, and twin emergencies of the Great Depression and World War II.”

According to the authors, prior Fourth Turnings were monumental events:

The 1760s were followed by the American Revolution, the 1850s by the Civil War, the 1920s by the Great Depression and World War II. All these unraveling eras were followed by bone-jarring crises so monumental that, by their end, American society emerged in a wholly new form.

Each time, the change came with scant warning. As late as December 1773, November 1859, and October 1929, the American people had no idea how close it was. Then sudden sparks (the Boston Tea Party, John Brown’s raid and execution, Black Tuesday) transformed the public mood, swiftly and permanently.

Whether it is a contested election, or the potential for a Civil War (discussed in July) after, America is entering it’s Fourth Turning.

C. A Few Things Worth Checking Out

1. Ray Dalio on capitalism’s crisis: The world is going to change ‘in shocking ways’ in the next five years.

2. Obvious Things That Are Easy To Ignore - by Morgan Housel

3. The team at a16z started a new podcast series on biology. Their 1st episode was on the biology of Aging.

4. Dr. Nir Barzilai (expert on Metformin) was on the Peter Attia podcast discussing longevity, immune enhancement and COVID-19.

5. Square is a truly innovative company. Jim McKelvey is the co-founder of Square, and in his book “Innovation Stack” he asks what do all truly innovative companies have in common?

6. On Monday I interviewed the author and spiritual teacher Deepak Chopra on his life, what he’s learnt and his new book Total Meditation (a great read). We finished with a short meditation.

"Success is largely the failures you avoid.

Health is the injuries you don't sustain.

Wealth is the purchases you don't make.

Happiness is the objects you don't desire.

Peace of mind is the arguments you don't engage.

Avoid the bad to protect the good."

- James Clear