<|im_start|>system
You are a helpful AI assistant.<|im_end|>
<|im_start|>user
What effect does turning on the Yamanka factors have in human cells?<|im_end|>
<|im_start|>assistant
A cell dosed with the Yamanaka factors erases the marks on the epigenome, so the cell loses its identity and reverts to the embryonic state. Erroneous marks gathered during aging are also lost in the process, restoring the cell to its state of youth. Dr. Yamanaka shared the 2012 Nobel Prize in medicine for the work.

But the Yamanaka factors are no simple panacea. Applied to whole mice, the factors made cells lose their functions and primed them for rapid growth, usually cancerous; the mice all died.

In 2016, Juan Carlos Izpisua Belmonte, of the Salk Institute for Biological Studies in San Diego, found that the two effects of the Yamanaka factors — erasing cell identity and reversing aging — could be separated, with a lower dose securing just age reversal. But he achieved this by genetically engineering mice, a technique not usable in people.

In their paper on Tuesday, the Stanford team described a feasible way to deliver Yamanaka factors to cells taken from patients, by dosing cells kept in cultures with small amounts of the factors.

If dosed for a short enough time, the team reported, the cells retained their identity but returned to a youthful state, as judged by several measures of cell vigor.

Dr. Sebastiano said the Yamanaka factors appeared to operate in two stages, as if they were raising the epigenome’s energy to one level, at which the marks of aging were lost, and then to a higher level at which cell identity was erased.

The Stanford team extracted aged cartilage cells from patients with osteoarthritis and found that after a low dosage of Yamanaka factors the cells no longer secreted the inflammatory factors that provoke the disease. The team also found that human muscle stem cells, which are impaired in a muscle-wasting disease, could be restored to youth. Members of the Stanford team have formed a company, Turn Biotechnologies, to develop therapies for osteoarthritis and other diseases.<|im_end|>
<|im_start|>user
CAn you describe in detail how the Yamanka factors work?<|im_end|>
<|im_start|>assistant
The Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are a group of protein transcription factors that play a vital role in the creation of induced pluripotent stem cells (cells that have the ability to become any cell in the body), often called iPSCs. They control how DNA is copied for translation into other proteins.

They are sometimes referred to as (OSKM genes). In 2006, Professor Shinya Yamanaka generated iPS cells from human adult fibroblasts, and, having started with 24 transcription factors known to be important in the early embryo, he and his research team whittled that down to 4 key transcription factors – Sox2, Oct4, Klf4 and c-Myc.

The factors are highly expressed in embryonic stem cells, and their over-expression can induce pluripotency in human somatic cells. These factors regulate the developmental signalling network necessary for embryonic stem cell pluripotency.

Yamanaka factors are often used to transform an adult cell into induced pluripotent stem cells; these have become important tools in longevity research, but they are a double-edged sword, as over-exposure can lead to a cell’s identity being erased.
The discovery of the Yamanaka Factors and the ability to generate iPSCs has had a significant impact on the field of aging research and the development of therapies for age-related diseases. By generating iPSCs from adult cells, researchers are able to create an “unlimited” supply of cells for use in regenerative medicine, drug development, and the study of cellular aging.

Using the Yamanaka factors could allow us to make the clock tick backwards, moving from aging research to epigenetic rejuvenation research.<|im_end|>