Turning Back the Cellular Clock

It’s 7:00 a.m. on a Wednesday morning and you’re shuffling up the stairs and out of your local subway station, fatigued from the four hours of sleep you got last night. Your phone vibrates and you take it out of your pocket. It’s a Google Classroom notification that reads “Ms. Smith posted a new material: Homework for Thursday, Quiz on Friday.” With a defeated expression, you groan, “God, I wish I was six years old again.”

It’s your lucky day! Scientists from the Babraham Institute at Cambridge have created a new technique—maturation phase transient reprogramming (MPTR)—that can do just that. Unluckily, however, the good news is from 53-year-old skin cell donors, not you.

Earlier in April, Diljeet Gill, a Ph.D. student at the Babraham Institute, and his supervisor, Wolf Reik, a leading authority in the epigenetic field, took their discoveries to the science journal “eLife.” They discussed the creation of the MPTR method, in which reprogramming factors are selectively applied to somatic cells until the desired regeneration point is achieved.

The origins of the MPTR technique stem from the late 1900s, when researchers at the Roslin Institute in Scotland developed the method of turning adult mammary gland cells from a sheep into an embryo. They created Dolly, the first mammal cloned from an adult somatic cell. Seven years later, the Dolly technique was simplified by professor and Noble Prize laureate Shinya Yamanaka at Kyoto University, who created the induced pluripotent stem cell (IPS) method. The method involves adding chemicals to adult cells for 50 days, turning the adult cells into stem cells.

However, both of these methods were unable to benefit patients directly as the stem cells must be regrown into the cells and tissues that a patient may require. In other words, cells treated with IPS lose their original cell type and functionality, which proved to be too complex for medical use.

Setting out to create embryonic stem cells that can divide into any type of cell in the body, Reik and Gill’s team created the MPTR technique when they used Yamanaka’s IPS technique on 53-year-old skin cells, but cut the 50-day chemical bath period to only 12 days. The researchers found that age-related changes in the skin cells were removed and the cells temporarily lost their identity. However, after allowing the cells to grow under normal conditions, the cells displayed normal skin behavior and returned to their previous states, except for one small difference: the skin cells now matched the profile of skin cells 30 years younger. The 53-year-old skin cells appeared and functioned like 23-year-old skin cells.

The potential applications of MPTR are linked to the difference in the capabilities of re-youthed versus old, damaged cells. The skin cells that were tested were fibroblasts that produce collagen, a molecule found in bones that provide structure to tissues while healing wounds and moving into areas that need repairing. The rejuvenated fibroblast skin cells produced more collagen and moved into gaps (wounds) in artificial layers of cells faster than control, older cells that did not undergo MPTR. Such results provide evidence that one day, this research may be used to create cells that are more efficient at healing wounds. The method provides added relevance to the medical field because the cells would not be rejected by the patient’s body since the cells would be their own. The cells could help speed up healing time in burn victims and may eventually extend human life with further research.

The technique has also recently been applied to restoring the pancreases of genetically modified mice. If applicable to humans, the technique may potentially fight diabetes and other diseases linked with aging, such as Alzheimer’s disease. Another trial rejuvenated the APBA2 gene linked to Alzheimer’s disease and showed promising improvements.

Unfortunately, the team has been unable to take the technique to a clinic for true medical use because MPTR was found to increase the risk of cancer because it creates lasting genetic changes within cells. However, Reik is confident that with the newfound possibility of rejuvenating cells, his team can find a safer alternative. If they are successful, the MPTR technique will become a revolutionary turning point in regenerative medicine.