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Introducing David Sinclair, The Einstein of Longevity?

David Sinclair just came out with a book, Lifespan. He’s one of the experts I’ve been following most closely in longevity, next to Peter Attia and Aubrey de Grey, due to his extensive list of accomplishments across disciplines, all tunnel-visioned towards this problem. He’s been heads-down on solving aging for over thirty years, as a professor and published researcher at Harvard, co-founder of the journal Aging, co-founder of the Academy for Health and Lifespan Research, and advisor/founder of multiple biotech companies. All this and more is enough to consider him at the pinnacle of defining and solving aging today.

I’ve been keeping a pulse on his research, media appearances, speaking engagements, etc. so was super pumped to get my hands on a collection of all his thoughts and work in one place. I’m about halfway through, I’ll write more thoughts once I read through all sections (last section is on the societal implications of indefinite healthspan and lifespan, intrigued to read his take). He’s also been going on a tear promoting it, getting on the top podcasts (e.g. Peter Attia, Joe Rogan, Lifespan.io, David Asprey) and providing good overviews, a few fascinating points stood out to me that I’ll bring up here.

We’re closer to forever than we think

The first thing that stood out is how close he believes we are to having the option to live to 200…500…1000 or longer. David references an eye-opening stat (so eye-opening even Attia questioned it, David said he’ll double-check and tweet it) that every month we stay alive, a week is added to our life due to how quickly the research is progressing. He posits that if he can just keep himself alive until 100 using the tools we have today, at that point, in 2069, there’ll be technology to support living to 4000 or beyond.

I get it, sounds crazy

When I relay stats like this to people I get two forms of information-lacking push backs. The first is a dismissive headshake and hand wave to the truth in it, discounting it as implausible, science fiction, stuff for movies or still 100s-1000s of years away. The second is that they wouldn’t want to live to 4000 even if they had the choice. Both valid responses if you aren’t privy to the underpinnings of what’s really going on behind closed lab doors today, the mountains of research both in the works and already published, and how it’s relevant for not just our duration of life but also our quality of life. Even my most curious, wide-eyed, visionary SF friends doubt the feasibility in it. I get it because I felt the same way before diving deep into this problem, narrowing my focus from consumer health tech to longevity-targeting science and technology about a year ago.

Most scientists don’t care about limelight and hype, they care about results. So even though the progress is excitingly far along, the general populous is in the dark because there’s nothing definitive, comprehensive, or commercialized yet. But we’re getting closer, keep reading for specifics.

This will be big…really big

Just as Wilbur and Orville Wright worked tirelessly on their flying machines in Kitty Hawk while little to no one knew the progress they were making until they were in the air, David argues the same is true for longevity. Scientists are making new discoveries every day that move the needle closer and closer to the most groundbreaking development in human existence. The ability to extend our healthspan and lifespan hundreds to thousands to indefinite years will happen slowly, then all at once and it will shake humanity at its core. Sinclair eloquently puts it “It is a time in which humanity will redefine what is possible; a time of ending the inevitable. Indeed, it is a time in which we will redefine what it means to be human, for this is not just the start of a revolution, it is the start of an evolution.”

But first, what is aging?

Death is the only problem we face that’s entirely pervasive. Everyone dies and most every person fears death and the debilitating struggles that come before it, often 10-20 years of painful physical and mental degeneration. It’s a big problem wrought with complexities. The initial focus from David and his labs, another reason I like this guy, was getting to the first principles of aging. What is it? Why does it happen? He’s come up with a single theory, one he calls the Information Theory of Aging, inspired by Claude Shannon an MIT electrical engineer who wrote The Mathematical Theory of Communications.

David’s Single Theory

The Information Theory of Aging posits that aging is simply a loss of information, and to reverse aging we need to remind cells of the information they’ve lost. Specifically, our epigenetic information. Where our genome is the computer, the epigenome is the software. Every cell in our body has the same copy of DNA, when we’re just a little fertilized egg in our mother’s womb we’re an amorphous blob of 27 billion identity-less cells with the same DNA. What happens as we develop a functioning body is these cells get assigned methyl groups with the help of proteins called sirtuins, which tag the DNA with “I’m a skin cell” or “I’m a liver cell” etc. and effectively turns on or off genes that are relevant for a skin cell or liver cell respectively. As we age, these methyl groups get damaged or lost and could cause a liver cell to start acting like a skin cell or a brain cell to act like a liver cell etc., making a bunch of junk noise in our bodies that causes all sorts of issues.

The Horvath Clock

This discovery led to Steve Horvath developing the most effective biological clock used in labs today, the Horvath Clock. This analyzes DNA methylation to determine our rate of aging, thereby estimating our age of death given the lifestyle at the time of submitting a blood sample. Fascinating and huge commercial opportunities there, but yet to be FDA-approved so no health-related information can be provided to consumers from the results yet. Side note: check out this article by Nature referring to a study published in AgingCell two weeks ago by Horvath and his team, it’s been getting a lot of hype in the longevity community due to unveiling the first evidence of reversing the biological clock using a cocktail of human growth hormone (hGH), metformin, DHEA, vitamin D3, and zinc. Albeit, it was a small, nonrandomized, personalized study done on just 9 men for 1 year so in my opinion (and Attia’s) it’s an interesting preliminary study but requires a lot of follow up.

It’s alone exciting and powerful that David and his teams were able to come up with this single theory. Although it’s one among many and I could name a few aging scientists who’d argue against it or for their own, I’m focusing on David’s here. So what’s next? If this tells us why we age, what can we do about it? By reminding our cells of the information they lost, i.e. restoring what they acquired as a baby—methyl groups that assigned each cell a path and a purpose.

According to David, our cells carry a copy of this somewhere, like a backup disc of what their original tag was. It explains why cloning works. The focus now is to reprogram our cells to think they’re younger by reverting them back to their original copy. David is studying that today.

Sirtuin accelerator: Resveratrol

In the meantime, there are potential ways we can delay this disc scratching and information loss—by bolstering our sirtuins. Sirtuins are protectors of the genome and epigenome. They lose activity as we age. Certain molecules have been found to accelerate and fuel their activity. For accelerating, there’s Resveratrol (or a similar molecule, pterostilbene). And sadly, no we can’t get there just with red wine, you’d need about 100 glasses to get the dose of resveratrol that’s proven to be effective. There are many commercially available resveratrol or pterostilbene supplements, David takes 0.5 g of resveratrol in powder form every morning.

Sirtuin fuel: NAD

For fuel, there’s NAD. NAD is a crucial signaling molecule used in much of our body’s chemical reactions, without it we’d quickly drop dead. It’s a signaling molecule that tells us when we’ve exercised, when we’re hungry, and lots more. It’s also vital for sirtuins to function, i.e. the fuel. We need them more as we age, yet they (very ineptly) deplete as we age. If we can replace NAD levels, we turn on defenses against information loss and boost DNA repair. How can we boost NAD? Still a lot of speculation around this because no long-term, randomized, human clinical study has been done but scientists say supplementing NAD precursors (NR or NMN) may do this.

NAD Boosters: NR or NMN

NR is part vitamin B3 partly a piece of DNA. When it gets into the cell, it becomes NMN, which is then turned into NAD. Some companies currently sell supplements containing NR or NMN that claim to boost NAD. (e.g. Elysium Health, MasterMind). But there are still so many unknowns, here’s a useful article on the summary of current research on NAD-boosting supplementation. David takes 1 g of NMN every morning.

Caveat: These may only be relevant for the old or sick

Many of the studies done to test the effects of NAD boosters have shown that it only benefits people with a compromised immune system or weakened biological state due to illness (ALS, cancer, vision loss, diabetes, obesity) or age (>50), and may do little if anything to a young, healthy individual. E.g. one done on mice showed that NR increased running speed and cardiovascular health in the old mice but not the young. The same is debated for rapamycin and metformin.

There’s more to learn. What do we do till then?

Since most scientists aren’t yet confident enough to prescribe recommendations, I’ll tell you what I’m doing based on everything I’ve read on this. I’m focused on optimizing the 6 pillars of health—sleep, diet, exercise, mindfulness, belonging, and purpose—to survive and thrive until around 50, at which point I’ll reassess the science behind NAD-boosters, metformin, and rapamycin. The goal is to make it to the maximum age of around 100, at which point I fully expect a toolbox of supplements, surgeries, and/or therapies to be available that will take me far beyond that.

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