We do not have to die

What is it about?

All cells in our body have a relatively short lifeline. The life of some of the major building block of cells, such as proteins, is even shorter. Many cells and their constituents are replaced every day. Thus, when we wake up every morning, we are practically newborn people. If the biochemical mechanisms of rejuvenation work perfectly and we do have any deadly accidents, we should ideally live forever. However, we do not. Why? The main reason is in the mechanisms of cell death and DNA replication. According to contemporary science, the process of programmed cell death, apoptosis, leads to morphological cell changes and death. Some of these changes are blebbing, cell shrinkage, and nuclear fragmentation 1. During the fragmentation, chromosomes are packed in so-called apoptotic bodies that are expelled outside of the dying cell. The phagocytic cells engulf and digest the apoptotic bodies and destroy the chromosomes. To sustain life, the dead cell needs to be replaced. This replacement is assumed to occur by the replication of stem cells. The stem cells divide and a daughter cell replaces a dead cell. Every time a stem cell divides and its DNA replicates, it has to copy and transmit the same sequence of 3.7 billion nucleotides 2 to its daughter cells. While most DNA replicates with reasonably high accuracy, mistakes (mutations) do happen 3. The reported rates of mutation during the replication of human DNA is one mistake per 100 to 1000 nucleotides 4. As about 50 and 70 billion cells die each day due to apoptosis in an average human adult and 6 billion bases are in the human genome, one can estimate that in the worst-case scenario, mistakes accumulated for 30 years can reach up to 20% of all 37 trillion cells of the human body. Of course, not all mutations are harmful, and DNA repair fixes many mistakes, but some of the mutations could cause cancer. Thus, the main “evil” in our life is the DNA replication that causes mutations. It seems impossible to replenish naturally dying cells without cell division and replication of DNA, however, it is quite possible! Sixty years ago, when stem cell science was in infancy, a Korean scientist Bonghan Kim discovered and studied a new primo vascular system (PVS) with the main function of regenerating cells and tissues. The PVS is composed of very thin (diameter, 20–50 μm) vessels and small (<1500 μm) nodes that are connected to primo vessels. He reported that the replacement of dying cells could be achieved without cell division and replication of DNA by recycling of the DNA of the expiring cells 5. According to Kim’s model, the cell that is preparing to die experiences chromatin condensation and packing into membrane-bound capsules; the deformation and rupture of the nuclear membranes release these capsules into the cytoplasm; and ruptures of the external membrane releases the capsules to the outside. Kim named these capsules sanals, and claimed that each sanal contains a single chromosome. So, if the dying human cell produces 46 sanals, these sanals are subsequently used for cell regeneration. The process, described by Kim, is almost identical to apoptotic cell death and the generation of apoptotic bodies but it has a major difference: phagocytic cells destroy apoptotic bodies; however, in contrast, PVS protects sanals and uses sanals to regenerate cells. The expelling of the apoptotic bodies outside and digesting them by phagocytic cells is the end of a cell’s life, but the release of sanals that preserve DNA is the beginning of a new cell’s life. Kim further showed that the expelled cell sanals are collected by the PVS, assembled into the cell with a complete genome, and then positioned to replace a dead cell. The most significant factor in this process is that the DNA is recycled and not duplicated or mutated. Kim demonstrated that both DNA duplication and DNA recycling mechanisms coexist for the replacement of dead cells. The DNA recycling method provides no errors and promises a longer life. In my laboratory, we were able to reproduce some of the experiments described by Bonghan Kim 6. We have found conditions when some blood cells in vitro undergo the process of death with the release of sanals, small uniform ~1-µm size subcellular bodies, that tend to assemble in groups. We further harvested rat primo vessels and nodes, and then, from the nodes, we extracted and purified sanals, which in a high-resolution microscope looked like micron-size bubbles carrying a speck of matter inside. We have demonstrated that sanals merge and create cell-like structures. 7 We plan to carry out DNA and RNA analysis of sanals and observe the movement of labeled sanals in the cell-sanal cycle in the animal models. We hope that in the future, the practical application of the PVS system will save and prolong lives. References 1 Levi, C. A. et al. Apoptosis: Its Physiological Implication And Therapeutic Possibilities. IOSR Journal of Pharmacy and Biological Sciences 9, 38-45 (2014). 2 Bianconi, E. et al. An estimation of the number of cells in the human body. Annals of Human Biology 40, 463-471, doi:10.3109/03014460.2013.807878 (2013). 3 Pray, L. DNA Replication and Causes of Mutation. Nature Education 1, 214-219 (2008). 4 Johnson, R. E., Washington, M. T., Prakash, S. & Prakash, L. Fidelity of human DNA polymerase eta. J Biol Chem 275, 7447-7450 (2000). 5 Vodyanoy, V., Pustovyy, O., Globa, L. & Sorokulova, I. Primo-Vascular System as Presented by Bong Han Kim. Evidence-Based Complementary and Alternative Medicine Volume 2015, 17 pages, doi:10.1155/2015/361974 (2015). 6 Vodyanoy, V., Pustovyy, O., Globa, L. & Sorokulova, I. Evaluation of a New Vasculature by High Resolution Light Microscopy: Primo Vessel and Node. arXiv:1608.04276v1 (2016). 7 Kang, K. A., Pustovyy, O., Globa, L., Sorokulova, I. & Vodyanoy, V. in Oxygen Transport to Tissue Xl Vol. 1072 Advances in Experimental Medicine and Biology (eds O. Thews, J. C. LaManna, & D. K. Harrison) 413-418 (Springer International Publishing Ag, 2018).

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