In late 2020, the Sinclair lab at Harvard Medical School published a breakthrough in which molecular biologists were able to reverse poor eyesight and damage to the retinas in old mice. This was achieved by altering the epigenome of adult DNA skin cells to return them to their original state as embryonic stem cells using proteins known as Yamanaka factors. The altered cells were then introduced into the retina, where they were activated by an antibiotic. Once activated, they begin repairing the damaged tissues and simultaneously replicating healthy tissue.
The results weren’t just promising; they were astounding. Elderly mice with severe retinal degeneration were now able to see as well or better than their own children. Since that time, the team has restored brain, muscle, and kidney cells in mice using the same technique. Given time, scientists may be able to do the same for humans as well.
Let’s delve a little deeper into how that works and what that might mean for the human population.
Understanding the Process
The rejuvenation procedure described here employs powerful tools in molecular biology.
Stem cells are unique from the other cells in our body in that they can divide and self-replicate. When a stem cell divides, it can either produce two new stem cells, two non-stem cells, or one stem cell and one non-stem cell. Humans produce two types of stem cells:
Adult Stem Cells
Most adult tissues contain a small number of adult stem cells. They are at the ready to replace cells lost through injury, disease, or normal wear and tear. Adult stem cells are more restricted in what they can become than embryonic stem cells and often remain dormant until needed.
Embryonic Stem Cells
These stem cells are normally only present during the first 3 to 5 days of an embryo’s existence. At this point, the fertilized egg is known as a blastocyst and has just started dividing. Embryonic stem cells, unlike mature stem cells, are pluripotent, meaning that they could develop into any type of human cell. Because of their pluripotency, embryonic stem cells can be employed to regenerate or repair diseased tissues and organs. The use of embryonic stem cells is controversial in some circles as the cells must be harvested from a blastocyst.
What Are Epigenomes?
The term epigenome can refer to a multitude of chemical compounds that are able to affect a person’s genome. These chemical compounds are able to turn the genes within the DNA on or off, changing the overall expression of the genome. Some of these epigenomes are passed down from parent to child, others can become active or inactive due to environmental factors or lifestyle choices.
Infectious diseases, smoking, and dietary choices can all have an effect on an individual’s epigenome. Changes to the epigenome can have a number of different effects. This may include the possibility of uncontrolled cell growth, better known as cancer.
Yamanaka Factors
As we age, our cells change. Telomeres, the protective structures at the end of each chromosome, shorten, and the cells become less able to divide. They function less optimally and regenerate more slowly.
Yamanaka factors, named after the Nobel Prize-winning scientist that discovered them, Dr. Shinya Yamanaka, are a group of four key protein transcription factors that control how DNA is expressed. They are made up of four genes listed as Oct4, Sox2, Klf4, and c-Myc, and are also known by the acronym OSKM. When used in the right combinations, these factors were able to reset cells back to their embryonic state. Unfortunately, they also tended to induce uncontrolled cell growth.
When researchers introduced three rather than four of the Yamanaka factors, the cells were successful in rejuvenating and regrowing the damaged neurons in the eye without the propensity to trigger tumors. This is because using just three of the Yamanaka factors inhibited how far the cell reverted. Instead of the cell reverting to age 0, the cells reverted to between 50 and 70 percent of their original age. It’s this mechanism that helps prevent the overgrowth of cells that leads to tumors.
Of Mice and Men
For mice, the results of the original procedure were remarkable. The cells in the eyes of the old mice even grew new axons, the neural pathways from the eye to the brain. According to David Sinclair, Australian biologist and professor of genetics at Harvard Medical School, scientists may be tapping into an ancient regeneration system that is still occasionally activated without intervention. Animals like starfish and salamanders can spontaneously regenerate limbs. Even human children can regenerate an entire fingertip if stem cells from the bed of the fingernail are still present.
The cells that were reset did not revert to their aged state, but they started aging again at a normal pace. This meant that for mice, the renewed vision lasted for just a few months. Scientists were, however, able to repeat the procedure and reset the animals’ cells again after they had aged the second time.
Human Applications
Unfortunately, there are still a few hurdles to overcome before this type of rejuvenation is available for the human population. And these tools are not without their drawbacks. For instance, though earlier experiments were successful in rejuvenating the organs they were targeting, they also tended to cause cancerous tumors to form.
Human trials are in the early stages, but it will be years before the results are known. Another caveat is that they have only been able to rejuvenate a few organs at a time, rather than the whole mouse, as yet, anyhow. While the ability to reverse aging in one or more organs in humans appears to be on the horizon, that horizon is likely at least a decade or two in the future.
Epigenetic Anti-Aging Steps to Take Now
Fortunately, we have also learned that our lifestyle and environment play a large role in which epigenetic messages are shared with our DNA. Traits that can reverse the effects of aging on our cells include:
- Consuming fewer calories
- Eating more plants
- Getting enough exercise
- Maintaining muscle mass
- Managing stress
- Sleeping enough
According to Sinclair, he has been able to reverse some of the effects of aging in his own cells. He has done this by embracing a healthier lifestyle and including supplements in his daily routine. Some supplements in his diet include Vitamins D and K2, resveratrol, and nicotinamide mononucleotide.
The Takeaway
While scientists have made huge leaps forward in our understanding of aging and how to reset aged cells, there is still a great deal of knowledge that we don’t yet have. Treatments like those used on the experimental mice in this study appear to have great promise for people as well. They are unlikely to be proven safe and effective enough to be available to the general public for decades, however. In the meantime, managing your health and lifestyle choices is the most effective way to slow or reverse the effects of aging.
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