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What if you could reverse your biological age? Turn back the clock to an earlier, youthful age?
Epigenetic reprogramming is one of the key technologies that may allow us to reverse aging and extend human healthspan.
But what exactly is epigenetic reprogramming and how does it work?
Dr. David Sinclair, Professor of Genetics at Harvard Medical School and author of Lifespan, is perhaps the world's leading thinker on age reversal. I can't think of a better person to describe the details of epigenetic reprogramming—and the promise it holds for all of us.
In today's blog, based on some of my recent conversations with Dr. Sinclair, I'll discuss his Information Theory of Aging, what may ultimately be possible with epigenetics, and why you have more control over your longevity than you might think.
Epigenetic reprogramming, along with the 10+ root causes of aging, is a key topic I explore every year during my Longevity Platinum Trip.
Let's dive in…
A Brief History of Epigenetics
Our genome remains unchanged throughout our lifespan. From birth through age 80 or more, our genetic sequence—the 3.2 billion letters of DNA we inherit from our parents—stays the same. Yet, we look different as we age and develop diseases later in life.
Why is this? Why do we look different and develop disease while the software of life, our genes, is unchanged?
The answer lies in our epigenome, which controls the expression of our genes (“epi” coming from the Greek word for “above”). While our genes don't change over time, the way they are turned on or off—known as epigenetics—does.
In 2006, Shinya Yamanaka's groundbreaking discovery showed that just four genes could turn adult cells into age-zero stem cells, capable of repairing or replacing any tissue in the body. This Nobel Prize-winning finding opened the door to erasing decades of epigenetic damage.
A decade later, Juan Carlos Izpisua Belmonte from the Salk Institute took this further by activating all four “Yamanaka factors” in prematurely aged mice. After refining his approach, he achieved “molecular rejuvenation,” refreshing the animals' mitochondria and increasing their lifespan by an astonishing 30%.
Building on these discoveries, Dr. David Sinclair's Harvard lab made significant strides in 2019. They activated three of the four Yamanaka factors in mice with age-related glaucoma, a condition that typically leads to irreversible vision loss. Remarkably, the treated mice—dubbed REVIVER mice—had their sight restored. This marked the first treatment to reverse vision loss in a glaucoma model, and none of the mice died during the process.
Sinclair's team then put his Information Theory of Aging to the test using the “epigenetic clock” developed by UCLA's Steve Horvath. This clock measures methylation, a chemical change that accumulates with age, much like rust on a car. After activating the three Yamanaka factors, the REVIVER mice showed less methylation—they had actually become younger, and their glaucoma had vanished.
Sinclair's findings suggest that the epigenetic clock doesn't just measure time, but can also control it.
The Information Theory of Aging in Action
This nascent field of epigenetics made a huge leap forward in January 2023 when Dr. Sinclair and his colleagues published a landmark paper in the prestigious scientific journal Cell.
They showed that epigenetic change is a major cause of mammalian aging—and tweaking the epigenetic information of mice can actively speed up or reverse the effects of aging.
According to the Cell paper, they were able to both accelerate and reverse the effects of aging in mice, and restore some of the biological markers of youthfulness in the animals.
This reversibility supports Dr. Sinclair's theory that the primary causes of aging are not mutations in DNA, but rather errors in epigenetic instructions.
Dr. Sinclair has long held the belief that aging is a result of losing crucial instructions that cells need to function, which he refers to as the Information Theory of Aging. He states, "Underlying aging is information that is lost in cells, not just the accumulation of damage. That's a paradigm shift in how to think about aging."
These latest findings appear to back up his theory, and Dr. Sinclair likens it to how software programs depend on hardware, but can sometimes become corrupted and require a reboot.
He adds, "If the cause of aging was because a cell became full of mutations, then age reversal would not be possible. But by showing that we can reverse the aging process, that shows that the system is intact, that there is a backup copy and the software needs to be rebooted."
Whole-Body Rejuvenation
So, if eventually a real rejuvenation therapeutic works for one tissue or organ, could it work for the entire body? Could we see whole-body rejuvenation?
I asked Dr. Sinclair this question when he was on stage with me at the Abundance Summit, and here's what he had to say:
"In mice, I'm shocked that what works in the eye, in the optic nerves, the nerve cells, works in the epithelial cells in the retina, works in the outer layer of cells on the retina, works in the kidney. If it works in all those different cell types, I think it's a universal process of biology to be able to be reset. And so that's why I'm not exaggerating when I think a whole-body reset is coming."
Why This Matters: You Have More Control Than You Think
"This is why I actually now bother to worry about my health. I thought we could affect it only slightly, but no. We really do have our longevity in our hands."
- David Sinclair, PhD, Professor of Genetics at Harvard Medical School
Today, and every year hence, exponential technologies are accelerating and we're in the steepest part of the curve in terms of biological breakthroughs coming from AI, quantum technologies, CRISPR, and gene therapies (just to name a few).
As Dr. Sinclair points out, "a number of new technologies will emerge which we cannot predict or even imagine today."
For example, in 20 years, I may want to reset my epigenetic age, and/or upgrade my body. The conversation may shift from maintaining our biological vessel towards designing disease-free, synthetic bodies or body parts.
But it turns out that as we await these new technological wonders, there are things we can do TODAY to reduce the effects of aging and increase our chances of intercepting these technologies once they arrive.
As Dr. Sinclair notes, "We know a lot about how to slow down the aging process … you don't just look younger, you actually are biologically younger. And that's why if you exercise, you eat right, you eat less often, you take the right supplements, you will be biologically younger and you'll actually stave off disease until much later."
Indeed, the older we get, the more important our habits and lifestyle become.
