Is biological age reversal really possible?
Is there an upper limit to the human lifespan?
I recently sat down with Dr. David Sinclair, Professor of Genetics at Harvard Medical School and author of Lifespan, to discuss these topics during a recent episode of my Moonshots and Mindsets podcast.
I opened with a question of how long might humans be able to live? Is there an upper limit? Sinclair’s answer was inspiring:
“There is no biological limit... of course there isn’t,” he began. “We are the same stuff as a whale that can live a lot longer than us (200 years), we’re built of the same stuff as tortoises, pretty much the same stuff as trees that can live thousands of years, it’s a software problem.”
“I’m putting my career on the line,” he continued. “It’s a software problem and what’s interesting about biology is that software encodes the ability to rebuild the hardware. So, we need to reset the software. And when we do that in my lab, we find that tissues regenerate in animals; Organoids, which are mini human organs, regenerate, they fix themselves and they function like they are new again. So it is, in my view, 99 percent a software problem.”
In this blog we’ll get into the question of why we age in the first place, based on Dr. Sinclair’s Information Theory of Aging. Then, we’ll zoom into drugs which may slow down our aging process, and peek into the FDA approval process for these and other emerging therapies.
Let’s dive in!
NOTE: Dr. Sinclair will be joining us at next month’s Abundance360 Summit for an engaging conversation on Age Reversal and Epigenetic Programming.
(This blog is written by Peter H. Diamandis, MD and Raiany Romanni)
Our genome doesn’t change over the course of our lifespan. When we are born, when we are 20, 50 or 80 years old, our genome sequence is identical. In other words, our genetic information—the 3.2 billion letters of DNA inherited from our mother and father—doesn’t change over time.
If that’s the case, why do we look different as we age? Why do we develop diseases later in life?
Those 3.2 billion letters of life code for about 20,000 different genes. While our genes don’t change over time, what does change is the expression of our genes—in other words, which genes are turned on and which genes are turned off—also known as our epigenome (“epi” coming from the Greek word for “above”).
This nascent field of epigenetics made a huge leap forward on January 12, 2023 when a landmark paper was published in the prestigious scientific journal Cell, by Harvard geneticist Dr. David Sinclair. In this paper, Dr. Sinclair and his colleagues 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 authored by Dr. Sinclair and his team, they were able to not only age mice on an accelerated timeline, but also reverse the effects of aging 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."
In his book Lifespan, Dr. Sinclair brilliantly points out that if we cloned a 65-year-old, the clone wouldn’t be born old—which says a lot about how their genetic sequence or information remains intact, even if this 65-year-old’s genetic expression and cell regulation mechanisms are presently malfunctioning.
Genetic mutations, in other words, seem not to corrupt our essential hardware. There is, as Dr. Sinclair points out, a “back-up copy” within all of us, which remains retrievable.
When asked when we might expect to see FDA approved “age-reversal” drugs, Dr. Sinclair’s response was that drug development “is hard...super hard.”
It often takes billions of dollars to complete clinical trials, often after many failed attempts.
But, Dr. Sinclair adds, health-span extending drugs may already be here. They just haven’t yet gone through the painstaking process of FDA trials yet.
"In my view,” Dr. Sinclair notes, “we've got some drugs already–Metformin, Rapamycin–that I strongly believe can slow down aspects of aging, so we already have some technologies. They're not evenly distributed. It's not available to everybody because most doctors are unaware or unwilling to prescribe these medicines to people who are healthy…but the data looks good."
Metformin is usually used on diabetic patients, while Rapamycin is often used to prevent organ transplant rejection.
But studies have shown that Metformin's effect on cellular metabolism and many other diseases that come with aging (diabetes, cardiovascular disease, cognitive decline) can substantially delay mortality.
So much so, that patients with diabetes and on metformin often live longer than patients without diabetes, not on Metformin.
Rapamycin similarly shows a delay in age-related pathology.
Yet, Dr. Sinclair explains, a number of safety and efficacy measures need to be cleared so that drugs can be approved for “healthy” patients.
What we're talking about is a radical departure from traditional medicine.
We've all come to expect that we go to the doctor for our once-a-year physical (if we're lucky); the doctor listens to our lungs and our hearts; and notes that our test results are not ideal, but natural “for our age.”
We don't fight against aging. We try and do a gentle landing, if you will.
The FDA, too, is an organization built around safety, and as such is risk-averse.
If the FDA approves a drug that inadvertently kills even one person, that one life is perceived as more valuable than all the lives lost by not approving a drug.
And, as such, until the science is rock solid, they're going to be hesitant to approve a longevity drug.
With advancements in AI, the drug development timeline is compressing. But still, much work remains to be done before we can democratize aging therapies.
Dr. Sinclair notes that the first step in having the FDA approve any drugs to slow, stop or reverse aging, is to have the agency recognize that aging is a disease.
He shared with me that the FDA is “surprisingly receptive to the idea that aging can be treated with a medicine, and they are still in favor of the opinion that if we can show that aging may be slowed with treatment, they would strongly consider approving that medicine for the treatment of aging.”
The $55-million Targeting Aging with Metformin (TAME) trial, run by Dr. Nir Barzilai at the Albert Einstein College of Medicine, aims to do just that: prove that aging itself can be targeted with an existing drug (Metformin).
Similar trials to evaluate the efficacy of Rapamycin and senolytic medicines are also under way or in planning stages.
Dr. Sinclair concludes by saying that “the FDA is a bureaucracy–a big organization with lots of rules and procedures, and those rules dictate how quickly we can move.”
Ultimately, increased pressure from the public and from politicians is essential “to increase the dialogue and help the FDA find a way to make it easier for us to get a drug on the market that's based on aging research.”
“If you’re offended by the idea that you have a slow, progressive disease, you’re in denial. If you think you can’t do anything about it, you’re even more in denial.”
- David Sinclair, PhD, Professor of Genetics at Harvard Medical School
If aging is a disease, then we’re all sick, and we’re all dying.
As Dr. Sinclair puts it, “aging is very, very risky.”
I half-jokingly added, “and it’s a known cause of death.”
Dr. Sinclair and I both agree that the longer we can “kick the mortality can down the road” (as one of our Twitter commentators put it)—the longer we can delay our perhaps inevitable end—the closer we will be to benefiting from next-generation age-reversal therapies, which will in turn add additional healthy years to our lives. Believing that is possible and maximizing your efforts towards that end is part of having a Longevity Mindset.
So, what’s your Longevity Mindset?
If we’re enjoying life, if we’re fulfilled at work and if we feel a sense of purpose in solving the world’s grandest challenges, then you’ll probably want to live longer to enjoy the future. As my friend and coach Dan Sullivan puts it, “one key to having a Longevity Mindset is having a future that is bigger than your past.”
And in calculating how long we may live, it’s important to remember that 20 years from now (say 2043), the world will look radically different.
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.”
By 2043, 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.
Regardless of our shifting conceptions of “health” and “disease,” the idea of being able to play with my great-grandchildren, live on the Moon, or travel to Mars is extraordinary.
Personally, it compels me to wake up each day and focus on my Massive Transformative Purpose (MTP) of increasing human healthspan, and on doing everything I can to “kick the mortality can down the road” for long enough that just maybe, new technologies allow me to keep “kicking it” indefinitely.
Click here to listen to or watch the whole conversation I had with Dr. Sinclair!
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Applications close and we go to Waitlist Only on Thursday, February 23, 2023.
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