How fit are your cells?
Within the cell nucleus, our genes are arranged along super coiled, double-stranded DNA molecules known as chromosomes. At the ends of the chromosomes are stretches of DNA called telomeres. They protect our genetic information, help in cell division, and associated with cellular ageing and cancer. Telomeres have been compared with the plastic tips on shoelaces, because they keep chromosome ends from fraying and sticking to each other, which would destroy or scramble an organism’s genetic information. Yet, each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive, enters into a senescent or growth-arrest phase and produces different products and it dies. The mechanism of this shortening process is not clear so far. However a recent novel research conducted by a group of cell biologists from UT South-western Medical Centre sheds light to this area. They demonstrated a unique looping mechanism of telomeres and their association with cellular aging, initiation and transmission of diseases. They found that length of telomeres are involved in the determination of silencing of certain genes early in life and activating them later when telomeres are progressively shortened, thereby contributing to aging and disease transmission processes. The group also observed that before the telomeres shorten to the critical length, the slow erosion in length has an effect on the cell’s regulation of genes that potentially contribute to aging and onset of disease. Particularly, the team showed that when a telomere is long, the end-cap forms a loop with the chromosome that brings the telomere close to genes, which were previously considered to be very far away to be regulated. Once the telomere and the far-away genes on the same chromosome are close to each other, the telomere can generally switch those genes off. Conversely, when telomeres are short after repeated cell-division, they do not form a loop. The distance between the genes and the telomeres increases. The telomere can no longer influence the target genes to switch them on or off. The scientists were able to identify three genes whose expression patterns are altered by telomere length. However they believe that this number is just the tip of the iceberg. Thus telomere shortening could be used as a timing mechanism to respond to physiological changes in very long-lived organisms, such as humans, to optimize fitness in an age appropriate manner. Experts think that this is a new way of gene regulation which is controlled by telomere length. The findings, published in the journal Genes and Development, required the researchers to develop new methods for mapping interactions that occur near the end-caps and to use an extensive array of methodologies to verify the impact.
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