Biomarker of Cellular Senescence
Replicative Senescence
Cell Cycle and Replicative Senescence — Hayflic’s limit
Early in life, nearly all of the body’s cells can divide. But this process doesn’t go on indefinitely. Cells have finite proliferative lifespans,After a certain number of divisions, they enter a state in which they no longer proliferate and DNA synthesis is blocked. For example, young human fibroblasts—structural cells that hold skin and other tissues together—divide about 50 times and then stop. This phenomenon is known as the Hayflick limit, This special aspect of cellular senescence is known as replicative senescence.
Normal Cell Cycle (cell division, proliferation) is regulated by 2 groups of counteracting genes — the proliferative genes and anti-proliferative genes (also known as tumor suppressor genes). A multi-layer control system is proposed as the intricate mechanisms that interact to maintain a balance between the two kinds of genes. Some gene’s function is to suppress (or silence) other genes. Mutations in these silencing genes have been found to affect the lifespan of yeast suggesting the role of replicative senescence in human aging and life span.
Telomere Shortening and Damage
Telomeres refer to the structure at the end of every chromosome. It contains the same short sequence of DNA bases (TTAGGG) which repeats thousands of times and pack itself into a structure to form the cap at the ends of chromosomes. Telomeres DNA sequences do not encode any gene for protein. Telomere is found to get shorter as a cell divides due to the mechanism that during mitosis, the extreme ends of chromosomes can not be replicated/synthesis by DNA replication protein system. So each time a cell divides, the telomeres get shorter. Over time, telomeres become so short that their function is disrupted, and this, in turn, leads the cell to stop proliferating. Average telomere length, therefore, gives some indication of how many divisions the cell has already undergone and serves as the molecular meters of cell division and cell’s age. Furthermore, besides its length, telomere’s 3-D conformation may also affect cell division and replicative senescence.
Telomerase is an enzyme which can enable cells to replace lost telomeric sequences and divide indefinitely, making telomere no longer shrink with each cell division. This enzyme was found to be abnormally active in cancer/immortal cells while it is not active in most adult cells (egg and sperm cells are among the exceptions). How the gene for telomerase is turned on in cancer cells is the area of research for cancer treatment.
