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- Shinya Yamanaka won the Nobel Prize in 2012 for his discovery of “Yamanaka factors,” which can revert cells to their embryonic state.
- The factors seemed promising for reversing the signs of aging, but they reset the age of cells much earlier.
- New research may stop the reverse-aging process at the precise time before the cell returns to its embryonic form, turning its clock back 30 years.
Fifteen years ago, scientists made a provocative discovery when they showed they could reverse the aging process in cells. By activating a set of four factors in the DNA, they reset the cell clock to zero, returning adult cells to their embryonic state. The factors were named the Yamanaka factor after their discoverer, Shinya Yamanaka, and a few years later, it won them the Nobel Prize. For the first time, scientists saw a glimmer of hope that aging could be reversed.
“It’s quite surprising if you think about it,” says molecular biologist Wolf Riek of the Babraham Institute in the United Kingdom. popular mechanics, “You can potentially reset the age of human cells to zero.”
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The scientists hoped that these cells could be used to repair and rejuvenate damaged organs, eliminating the signs of aging. Smaller, healthier nerve cells, for example, can take in for brain cells killed by a stroke, or collagen-boosting skin cells can be injected directly into stubborn wounds. The only problem is that Yamanaka factors reset the cells too far. A cell that is zero days old cannot send electrical nerve signals or produce collagen, or perform any other function. Like stem cells, it is nothing more than a drop of potential.
To overcome this, scientists are tinkering with time and looking for ways to stop the reverse-aging process at the precise time before the cell returns to its embryonic form. Previous efforts in mice have shown some promise, but the gains have been modest, with only three years or so reversing the clock.
But now, a group of scientists led by Rieck have shown they can turn back the clock by 30 years. This is the furthest person who has gone without going too far. In April, they published the results eLife,
What is new and interesting in this study is that they push cells into reprogramming in a time-controlled manner, said Manuel Serranoa molecular biologist at the Barcelona Research Institute in Biomedicine who was not involved in the study. tells popular mechanics, Serrano says that until now, scientists hadn’t really been able to control for the Yamanaka factors with much certainty.
To start, the researchers collected skin cells from middle-aged adults between the ages of 38 and 53. They specifically collected skin fibroblast cells, which are essential for wound healing and whose effectiveness declines with age. Using viral vectors, they injected Yamanaka factors (a set of four genes) into the cells and turned them on. Previous research has shown that it takes a total of 50 days for the Yamanaka factors to reset the clock to zero, and that between day 10 and day 17, the cells were 20 to 40 years old, respectively. The researchers decided to block the action of the Yamanaka factors, looking at the effect on cells between day 10 and day 17 during this period.
Epidermis and dermis of human scalp under 100X magnification. The epidermis is composed of keratinized stratified squamous epithelium. The color of gold is the stratum corneum made up of a tough, protective protein called keratin. The basal layer is on top of the dermis (blue). A flattening of the epithelial cells is also evident as they move towards the surface. The dermis is bluish in color and is composed of a large amount of fibrous connective tissue, irregular.
Getty Images Ed Reschke
At each pause, the researchers evaluated the biological age of the cells using molecular “aging clocks.” Changes in DNA that cause cancer, called epigenetic changes, were measured. They also measured collagen production because this protein infuses youthful skin with its distinctive firm and plump texture, but it declines with age. They also measured cell motility. When the skin is damaged, fibroblasts physically move into the wound to kick-start collagen production and begin the repair process. Fibroblasts slow down as they age, which explains why older skin takes longer to heal.
Scientists found the sweet spot after just 13 days. The cells were young, but still retained their ability to produce collagen and move quickly to the damaged areas. “Understanding that we can rejuvenate cells was amazing,” Ines Milagrea researcher at the Gulbenkian Institute of Science in Portugal and an author on the new studytells popular mechanics, “But the most exciting thing was to see that the cells were functionally small,” she says.
According to Milagre, the work is an important milestone and proof that Yamanaka factors can be corrected. However, she says we shouldn’t expect the technology to be available in a clinic anytime soon. Activation of Yamanaka factors can lead to cancer, and it is still unclear whether this process will work in other types of cells. “There are still so many unknowns,” she says.
Riek echoed these concerns and plans to develop a safer strategy. He thinks that by better pinpointing how Yamanaka factors work, he will be able to find downstream molecules that are turned on by genetic factors. By identifying those factors, which could be RNA or proteins, he could develop therapeutics that do not require tampering with genes in the cell, therefore reducing the risk of cancer and other side effects.
“We could call them ‘rejuvenation factors,’ and they would provide a safe way to rejuvenate cells,” Riek says.
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