Our cells' ability to function declines with age, striking interest into ways in which we could ‘rewind the biological clock’ and restore cells to their former efficiency.
Researchers in the Babraham Institutes Epigenetics research programme have developed a method to transiently reprogram cells based on work by Nobel Prize winner Shinya Yamanaka. Yamanaka was the first scientist to turn specialised cells into stem cells which have the unique ability to develop into any cell type. His method took 50 days and was based on cell exposure to four key molecules referred to as the Yamanaka factors.
By using these same 4 factors over a shorter time frame of 13 days, researchers have been able to halt the reprogramming part of the way through the process and thus not entirely erase the cell's identity. Over time, these partly reprogrammed cells regain their skin cell-specific function. Genome analysis showed that cells regained the characteristic markers of skin cells (fibroblasts), and this was confirmed by observing a recovery of their collagen producing ability.
There are many measures of biological age which can be used to determine the extent of the reprogramming. An epigenetic clock is one measure which is a biological test for the chemical tags present in the genome which indicate age. When these reprogrammed cells were tested, they matched profiles of cells that were 30 years younger.
The capacity to reprogram cells, making them biologically younger, whilst preserving their ability to regain specialised cell function opens up many therapeutic possibilities. A fibroblast is the most common type of cell found in connective tissue. They produce collagen, a molecule which is essential in providing structure to tissues and in healing wounds. The rejuvenated, and therefore biologically younger fibroblasts produced more collagen compared to control cells which did not undergo reprogramming. As well as this, the partially rejuvenated cells were found to more rapidly migrate to an artificially cut layer of cells. Both of these features provide a promising indication that the reprogramming of these cells could have use in improving their healing properties for treating wounds.
Other therapeutic possibilities include a role in the treatment of age-related diseases. It was observed that by reprogramming cells, the transcription levels of genes linked to conditions such as Alzeheimers, reverted back to levels which are associated with young cells. This observed reverse of ageing indicators in genes associated with diseases is particularly promising for the use of this process in regenerative medicine.
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