CONCEPTUAL ARTICLE
Why Do We Age?
Except for the heart, all organs in the human body have large numbers of cells dying and regenerating every day. These regenerated cells come from the self-replication and cell differentiation of stem cells; therefore, stem cells must divide repeatedly. However, the number of divisions of stem cells is limited, and each time a stem cell divides, it ages somewhat. Thus, our bodies slowly grow old in this way. So why is the number of stem cell divisions limited?
It turns out that in the cell nucleus there is a clock that limits the number of cell divisions, called “telomeres”. Telomeres are composed of multi-copy tandem repeat sequence DNA and proteins, including the tumor suppressor protein p53. The higher the p53 level, the more difficult it is for cells to divide. Each time a cell divides, the telomere array shortens by a small segment. Therefore, as telomeres gradually shorten, the p53 level in the cell becomes higher and higher, until the cell can no longer divide.
However, in some types of cells, whether they divide or not, telomeres do not shorten, yet the cells still slowly age. Therefore, besides telomeres, there should be another set of things similar to telomeres in the cell nucleus that regulates the process of cellular aging. After searching and searching, it was finally found: “ribosomal DNA (rDNA)”. Like telomeres, rDNA is also multi-copy tandem repeat sequence DNA, and it also binds p53. rDNA arrays shorten in both dividing and non-dividing cells, thereby causing the p53 level in the cell to become higher and higher. And so I proposed the “Telomere DNA and ribosomal DNA Co-regulation Model for Cell Senescence (TRCS)”: the fundamental cause of cellular aging is the shortening of telomere and/or rDNA arrays.