prompter: What effect does turning on the Yamanka factors have in human cells?

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.

prompter: What you just told me describes an experiment on mice. Tell me how it affects human cells.

assistant: Turning on the Yamanka factors in human cells has been found to modulate the expression of genes related to nutrient sensing and metabolism. This can lead to increased production of proteins that are involved in energy production, cellular growth, and repair. Additionally, it has been shown to increase the efficiency of energy production in mitochondria, which can lead to improved cell survival in stressful conditions.

prompter: CAn you describe in detail how the Yamanka factors work?

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.

assistant: The Yamanaka factors are a set of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) that can reprogram adult cells into pluripotent stem cells. When introduced into mature cells, these factors can activate genes that are typically only expressed in embryonic stem cells, thereby allowing the cells to revert to a stem cell-like state. From there, the cells can differentiate into any cell type in the body, which makes them useful for a variety of medical and research applications. However, the exact mechanisms by which the Yamanaka factors work are still not fully understood, and more research is needed to determine the best way to use these factors to create safe and effective treatments for a range of diseases.

assistant: The Yamanaka factors work by binding to specific regions of DNA, called enhancer regions, that control the expression of genes. By binding to these enhancer regions, the Yamanaka factors can modify the activity of the genes they regulate, leading to changes in the cell's behavior and fate. For example, when the Yamanaka factors are introduced into differentiated cells, they can activate genes involved in pluripotency and repress genes that maintain the cell's differentiated state. This results in the conversion of the specialized cells into iPSCs. The exact molecular mechanisms underlying the effect of the Yamanaka factors are still being studied, but they appear to involve changes in chromatin structure and the recruitment of other regulatory proteins to enhancer regions.

prompter: How can one induce the Yamanka factors?

assistant: The Yamanka factors can be induced in human cells through a variety of methods, including genetic manipulation, chemical compounds, and the use of viruses. Depending on the desired outcome, different methods may be more or less suitable for a given situation. Ultimately, the best method for inducing the Yamanka factors will depend on the specific application.

prompter: How are they involved with stem cells?

assistant: Turning on Yamanaka factors in human cells has the effect of inducing cellular reprogramming, converting the cells into a pluripotent state similar to that of embryonic stem cells. This can potentially have applications in regenerative medicine, disease modeling, and drug discovery.

prompter: when was that effect discovered and in which context ?

prompter: is it something I can do now ?

prompter: How where the Yamanaka factors discovered?