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The reprogramming of cells is a well-established technique in medicine and has been for over a decade now. It allows the en masse creation of patient-matched cells and is the basis for multiple current therapies.

Cellular Senescence and Cellular Reprogramming share mechanisms

Induced pluripotent stem cells (also known as iPS cells or iPSCs) can be created directly from adult cells. The iPSC technology was pioneered by Shinya Yamanaka, who demonstrated in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells[1]. These factors are Oct4, Sox2, Klf4, and c-Myc (OSKM), or as many call them, the Yamanaka factors.

Today, we have a new paper that discusses how induced pluripotency and cellular senescence, two of several possible cellular states, share similarities[2]. It is likely no surprise that the two states are closely related and that some of the mechanisms for one process are shared by the other. It appears that certain key signaling molecules are important in determining both cell fate and senescence.

Controlling cell behavior in living animals

As our understanding of guiding cell fate grows rapidly by the passing year, it has huge implications for therapies that seek to control cellular activities and encourage certain types of cells to be created. Research is now starting to move beyond the petri dish and to where cells are being programmed in situ in living animals.

In 2013, the Hallmarks of Aging proposed that epigenetic changes are a primary reason we age, but, at the time, the evidence in living animals was lacking[3]. All this changed in late 2015 when researchers induced pluripotency in living animals using the OSKM reprogramming factors, in much the same way as iPSC technology creates on-demand cell types outside the body. In this case, they only very briefly induced OSKM so that the aging markers in cells were reset but not long enough to cause the cells to revert to a developmental state.

The results of this first attempt to reprogram cells in living animals resulted in the cells of the mice becoming functionally younger in many ways and increased their healthy lifespan[4]. These results lend yet more support for the hypothesis that epigenetic alterations are one of the reasons we age and that reversing those changes is a path to maintaining health and tissue function as we age. A number of research teams are now exploring cellular reprogramming in living animals with a view to translating this to humans. We discussed the findings of this paper during our monthly Journal Club here.

Conclusion

This paper may be of interest to those wishing to delve deeper into the world of cell fate and understand the connection between cellular senescence and induced pluripotency. This builds on the knowledge we already have, and it is not difficult to imagine a time in the near future when we will have a very high level of control over our cells via reprogramming techniques.

If the hypothesis of epigenetic alterations being one of the causes of aging turns out to be correct, then that would be a real game changer. We are likely not too far off from determining if this is the case or not, and we may have the answer in the next few years, given the current pace of progress.

Literature

[1] Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 126(4), 663-676.

[2] Mosteiro, L., Pantoja, C., Martino, A., & Serrano, M. (2017). Senescence promotes in vivo reprogramming through p16INK4a and IL‐6. Aging cell.

[3] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[4] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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