by Patrick Cox
April 20, 2018
For the last few weeks, I’ve been having a conversation with a friend and reader about the difference between geroprotection and induced tissue regeneration (iTR). Based on those conversations, it’s clear that I haven’t done a good job of differentiating these two concepts.
This week, I’m going to refocus on ITR, which is Dr. Michael West’s strategy for activating the embryonic gene pathways that lie dormant inside our cells. There is no more important area of science, and the technology ought to be more widely known.
If it works the way West and his scientific team believe it will, it means that any cellular damage caused by disease, trauma, or aging can be reversed. While this may seem like science fiction, the fundamental science is actually pretty simple.
From Inactive to Active and Vice Versa: The Changing States of Genes
The entire genome exists within the nucleus of almost every cell in our body. Our genomes contain vast amounts of information and instructions, but not all of it is active in every cell. For example, the genes that make and manage our skeletal structure are present but not operational in our eyes and vice versa.
The genome is divided into two sections, the euchromatin and the heterochromatin. The active genes in a cell are located in the loosely packed DNA of the euchromatin, where they are readily available to create proteins, which is their job. The inactive genes in a specific cell are usually part of the heterochromatin, where DNA is tightly and safely packed away.
However, in some situations, DNA may change states. Genes that are active may be silenced and packed away; inactive genes may be unpacked and activated.
The biggest transformations happen at different stages of cell development. For example, the active and inactive genes change when the zygote becomes an embryo. They change again when the embryo becomes a fetus, about eight weeks after conception.
Let’s focus on what happens when the cells of the fetus become, biologically speaking, adult cells. This process is very brief and wouldn’t be noticeable to someone watching an ultrasound scan—but the genetic transition from embryonic to adult status is profound.
Embryonic vs. Fetal/Adult Cells
For our purposes, the most important difference between the embryo and the fetus is how cells replicate. A new embryonic cell gets its instructions from the original genetic blueprint of that specific cell as it exists in the central genome.
This eliminates the chance that a mistake or injury is copied and passed on to future iterations. If an embryo is harmed by some sort of trauma, it will revert to the developmental blueprint and create new damage-free cells.
That’s not practical for adult organisms, though. Adult cells, including fetal cells, reproduce by copying the last version of the genome. If there’s an error, it is copied and passed on. From the cell’s point of view, this makes sense because it requires less time and energy.
For that reason, the developmental, embryonic genetic blueprints are safely packed away in the heterochromatin… but they are not entirely inaccessible.
Under certain conditions, cells can access the original embryonic blueprints. In fact, many animals maintain that ability throughout their lives.
Biogerontologist Valter Longo, director of the USC Longevity Institute, demonstrated that diabetic animals put on his fasting mimicking diet (FMD) can regrow pancreatic beta cells, which store and release insulin when needed. He believes the same process occurs in humans who follow the FMD.
Longo also showed that the immunosuppressant drug rapamycin accesses the same developmental pathways. Rapamycin is the most studied of the compounds that extend healthspans and reverse, at least temporarily, the symptoms of age in older mammals. These are called geroprotectors, and I’ll get to them next week.
What iTR Is All About
Today, we’re focusing on induced tissue regeneration (iTR), which is Michael West’s technology for fully accessing the embryonic blueprints that are silent in the genomes of adult cells.
West, who is the co-CEO of BioTime (*see disclosure below) and CEO of its subsidiary AgeX, has identified the gene that orders cells to change the way they replicate. When that order is given, cells stop drawing on the embryonic blueprint and start copying themselves. From that point forward, any errors in the cell are copied and duplicated.
It reminds me of Nine Inch Nails’ Copy of A. The first line of the song is, “I am just a copy of a copy of a copy.”
In a very real sense, this is true. All of our cells are copies of copies. And because each copy includes all previous genetic errors, copies diverge more and more from that perfect embryonic original as we age.
West used powerful, deep neural network AI to identify the switch that stops embryonic cell replication and starts adult cell copying. It is the Cytochrome c oxidase polypeptide 7A1 (COX7A1) gene, which isn’t located in the central nuclear genome.
Rather, it is found in the mitochondria, the bacteria-like organelles we inherit from our mothers. In the original zygote that ultimately became you, there were mitochondria that had been passed down unchanged through centuries and countless generations.
Though my father warned me never to simplify biological processes by comparing them to electronic devices, I tend to think of the central genome as our computer operating system. The OS, however, is useless until it is given power and its original instructions by the boot firmware.
Mitochondria are biological, nonvolatile firmware. They have barely a dozen protein-expressing genes, compared to tens of thousands in the central genome, but they have major advantages.
First, they are a collective organism that reproduces through fission, so they are in a sense immortal. The mitochondrial colony in your body has existed, with only occasional mutations, since the dawn of human life.
Despite having fewer genes, the mass of mitochondrial DNA is roughly equivalent to that found in the central genomes of our cells. We have a lot of mitochondria, and they communicate with one another and the central genome using chemical signals.
When the first copy of your genome was being created through a merger of your mother’s and father’s DNA, the mitochondria in that original ovum were alive and functioning normally. Without their biological energy and preexisting instruction set, the brand-new genome couldn’t develop.
West’s plan is to tap that ancient firmware, giving the genomic OS instructions to reactivate the developmental pathways that were shut down when the embryo became an adult. He’s done it in cells. The Salk Institute has demonstrated the theory in mice. A scientist from the Weizmann Institute in Israel has tapped the embryonic circuitry to cause damaged hearts in animals to heal themselves.
Fully developed, this strategy would allow doctors to turn on embryonic healing powers to restore any tissue or organ to its perfect, youthful state. We believe that in humans, tissues and organs treated with iTR would be equivalent to those found in a healthy 27- to 29-year-old.
Ultimately, of course, the goal would be to rejuvenate the entire body—though it’s yet to be determined if that process could be done in a single clinical procedure. It may be that the body would have to be regenerated in stages.
There are still a lot of other unanswered questions about iTR, of course. Perhaps the biggest is whether iTR will lengthen telomeres, the biological clock that determines maximum age. I suspect we’ll get the answer to that question within a year or two because AgeX, the company that owns the rights to the platform, is close to launching now.
If iTR doesn’t restore telomeres, we may be able to reset that clock using a geroprotector that specifically hits the telomerase pathway. Next week, I’ll talk more about geroprotectors.
— The Difference between Anti-Aging and True Regenerative Medicine, Part 1 originally appeared at Mauldin Economics.
(*Disclosure: The writer has a position in this security. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)