The Greatest Revolution You Likely Haven’t Heard Of
We all grow old. Most of us view this as something inevitable — nature taking its course.
But what if I told you it doesn't need to be this way? What if we could not only live longer but also healthier lives? What if there was a universal solution to the diseases that plague us in our older age?
There is a revolution happening quietly at this very moment. Scientists are hard at work on technologies to reverse aging.
To better understand this revolution, let’s consult Dr. David Sinclair. He is a professor of genetics, a co-director of the Center for Biology of Aging Research at Harvard Medical School and one of the most prolific thinkers in the field of longevity research.
Dr. Sinclair is also an excellent educator and communicates complex subjects in a relatable way. Across his plentiful research, writing and talks he aims to make things as simple as possible, but no simpler.
In 2019 he published a book called Lifespan: Why We Age – and Why We Don't Have To, in which he thoughtfully examined the past, present and future of aging. It is a treasure trove of information and will help us navigate the terrain.
What is aging anyway?
Aging is notoriously hard to define. A common way to think about it is an organism drifting away from a healthy state with multiple systems slowly breaking down over time.
If this sounds similar to a definition of a disease, you are not wrong. The only reason why aging is not yet considered one is that it affects… more than half of the population, or 100% to be precise.
According to Dr. Sinclair, aging is a disease. If we universally recognize it as such and attract more funding to longevity scientists, we will be able to switch from doing whack-a-mole medicine — targeting age-related diseases one by one — to addressing a lot of them at once.
Why do we age?
In short — we don’t really know. Our best understanding thus far is that there is no single root cause of aging, but rather several interconnected ones. These are also known as hallmarks of aging, and there are at least nine of them (you can find the full list below).
One of them is genomic instability caused by DNA damage. Every day trillions of DNA breaks occur inside our bodies. We have built-in cellular machinery to fix those. But as we age, the damage piles up and becomes harder to repair.
Another is cellular senescence. Our cells eventually stop dividing. Some refuse to die and become inflamed. These cells are akin to zombies: they send out panic signals and inflame other healthy cells. They are called senescent cells, and as we grow old, we accumulate more of them.
Most scientists agree that if we address some or all of the hallmarks, we can slow down aging.
But there might still exist a single explanation. Aging, Dr. Sinclair claims, is a loss of information.
Information Theory of Aging
There are two kinds of information in our bodies. The first is genetic information (DNA). DNA is digital, as it is represented using a finite set of possible values — four nucleotides Cytosine, Thymine, Adenine, Guanine — much like 0s and 1s in our computers. This allows for storing and copying DNA with high precision.
But how can we have exactly the same genes in all of our cells, yet have entirely different cell types — skin, hair, eyes? That’s where the second kind of information comes in, also known as the epigenome.
It plays a key role in gene expression and controls which genes are turned on or off using special proteins. Much like a thread wound onto a spool, DNA is wrapped around these proteins. There is an almost unlimited number of ways in which DNA can be packaged, which makes this information analog.
Dr. Sinclair likens these to a DVD — the original information stored on a disk is digital, but the machine reading it is analog. The disruptions to epigenome with age — epigenetic noise — are like scratches on a DVD from its wear and tear.
Just as it’s harder to read a scratched surface, the altered epigenome causes cells to lose their identity and whole tissues and organs stop functioning correctly.
Could we find a way to restore the original epigenetic information that is lost when we are old? Can we polish the DVD?
Information theory of aging, as proposed by Dr. Sinclair, says that there should be a backup copy of that information preserved somewhere within us, and a correcting device that can use this backup to reset our cells to their younger state.
We still don’t know where or how the backup is stored, but we may have found the biological correcting device (our DVD polish).
Cellular reprogramming
There are four special genes, known as Yamanaka factors. These genes can reprogram any adult cells into embryonic-like stem cells that can be then transformed into any cell type.
Dr. Sinclair’s lab set out to regenerate optic nerves in mice using these genes — an ultimate test for rejuvenation. They chose one of the hardest tasks: the nerves of the central nervous system, which the optic nerves are part of, never grow back.
They damaged a mouse’s optic nerve with tweezers, causing the nerve cell connections to die and blinding the mouse.
Then they applied a treatment using three out of four of the Yamanaka factors. In two weeks the damaged nerves regrew and the mouse regained eyesight.
Optic nerve regeneration
Since then they were also able to restore vision in regular old mice. This technique, known as cellular reprogramming, has the potential to reset the epigenome of our entire body to its younger version, thereby reversing aging.
While this is a ground-breaking discovery and is likely the future of life extension, it won’t be available to consumers any time soon. But there are existing treatments out there that could help us live longer.
Existing Treatments
Metformin and rapamycin are two drugs that are safe and have been used to treat people for decades. They have also been shown to increase the lifespan of laboratory animals.
Metformin is taken by type 2 diabetic patients to lower blood glucose levels. It is one of the most widely used compounds in the world. Recently, researchers noticed that people taking it also tend to live healthier lives. So do the lab mice: metformin increased their healthy lives by 6% — 5 years in human equivalent.
Rapamycin was originally found on Easter Island. Ironically, it was already repurposed once: it was first meant to be an antifungal remedy. Today it is used to lower the immune system’s response during organ transplants, allowing the body to accept new organs. Small doses of rapamycin given to old mice gave them 9-14% longer lives, or an extra decade in human terms.
Turns out that both metformin and rapamycin mimic aspects of caloric restriction, which itself was demonstrated to increase lifespan in mice back in the 1930s. In other words, by taking them, you can fool your body into thinking that you are eating less without actually eating less.
Trials are underway for both metformin and rapamycin to prove their effectiveness in extending human lifespan.
The future
As my parents are getting older, I naturally worry about their health and well-being. And as I watch my grandparents get frail and lose the spark they once had, it emphasizes how precious the time with our family is.
A few months ago I didn’t even know it was possible to slow down or reverse aging. Then Dr. Sinclair took me on a whirlwind tour of progress in life extension. As I was reading Lifespan, the topics didn’t feel overwhelming — it felt like someone reassuringly put his hand on my shoulder.
Now I know that technology might be able to give my parents an extra decade or two of healthy life. And I can’t wait for all of the dinner conversations we’ll have and the trips we will take together when they are 100.
Hallmarks of aging
Dr. Sinclair lists the following hallmarks of aging in his book:
Genomic instability caused by DNA damage
Attrition of the protective chromosomal endcaps, the telomeres
Alterations to the epigenome that controls which genes are turned on and off
Loss of healthy protein maintenance, known as proteostasis
Deregulated nutrient sensing caused by metabolic changes
Mitochondrial dysfunction
Accumulation of senescent zombielike cells that inflame healthy cells
Exhaustion of stem cells
Altered intercellular communication and the production of inflammatory molecules