These are the results produced by a collaboration of 23 Italian universities on new frontiers of cells reprogramming, aimed to determine fate of healthy and pathological stem cells and define incredible regulatory activities of the code that organizes life: the epigenetic code.

The studies on functioning of the epigenetic code made it possible to understand that what had been studied was in fact the code of regulation of gene expression. This code is present in its totality and with all its different functions only at the moment when life is formed. In this moment this code could be studied and understood in its global functioning, even if subdivided and divided into different stages of differentiation. In fact if all the substances present in all the different stages of differentiation had been obtained, we would have had the entire epigenetic code available, that is the code able to regulate all the genes of all the cells that make up an entire organism. In other words we would have had the whole code that regulates life: the “Code of Life”. This possibility of studying the epigenetic code in its entirety exists only in the embryo and only in the moment when all the organs and systems differentiate. In that period from a single totipotent stem cell (the fertilized egg) there is a differentiation of all types of stem cells through various stages: pluripotent, multipotent, oligopotent cells, cells in process of definitive differentiation and finally completely differentiated cells. Once the organogenesis is over, it is no longer possible to study the entire epigenetic code in its whole extent and with its different functions. In fact, when the organogenesis is terminated, the epigenetic code is divided into various organs and tissues and every organ contains that part of the code which serves to control and regulate gene expression of the cells of that specific organ, and there is no longer a possibility of studying all the different and incredible functions of the “Code of Life”. Therefore only in that moment when it was decided to study the epigenetic regulation code, i.e. during the period of differentiation of various organs and apparatuses, it became possible to study all the different and incredible regulatory capacities of this code. And that is what has been done, choosing first of all an embryo as a study model for cell differentiation: i.e. in this case the embryo of Zebrafish.

The study of the entire epigenetic code and its functions has led us to fantastic discoveries. These different functions are here briefly described in order to make it clear what great opportunities the study of the code of life offers.

The different regulatory activities of the epigenetic code are listed below:

• Anti-Aging Activity
• Slowing of the multiplication and growth of cancer cells
• Prevention of Neuro-Degeneration

Preventing senescence with the help of growth and differentiation factors extracted from Zebrafish embryo:

Anti-Aging Action:

For the first time in the world it has been identified a fraction of the epigenetic code which has proved to be able to naturally maintain, without genetic manipulations, stem genes responsible for preventing cellular aging (these are the same genes that Shinya Yamanaka, who won the Nobel Prize in 2012, had artificially introduced within a retrovirus in a differentiated cell. This cell however cannot be used without risk precisely due to the undergone manipulations, which modify the cellular cyclicity and keep the cell in a phase of continuous multiplication. In our research, instead, the cells increase the duration of their life without being manipulated, based only on a physiological regulation of the stem genes. In fact if the administration of these factors is stopped, the cells return to age, thus demonstrating that they have not lost their cyclical nature and normal physiology). The cellular life increase occurs thanks to the impediment of telomere cutting, that is the terminal part of the chromosome composed of repeated sequences of DNA. The function of telomeres is to protect the termination of chromosomes, to allow cell division, to protect against aging and cancer. The telomere prevents the progressive degradation of chromosomes what could bring to the loss of genetic information: telomeres in this way act as a sort of biological clock, linked to a maximum number of DNA replications, at the end of which the cell becomes too old for being kept alive. At that point the cell undertakes the path of programmed cell death and thus concludes its life cycle. The factors isolated in our studies not only prevent the cutting of telomeres, thus lengthening the life span of cells, but also activate other genes, such as Bmi-1, which induce the synthesis of various proteins responsible for preventing cellular senescence.