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Why telomeres shorten and restoration strategies in aging

VIDEO SPONSOR - Longevity.Technology: https://www.longevity.technology/?utm... Telomeres are DNA repeats found at the ends of chromosomes. They serve to maintain chromosomal stability. The caveat is that they shorten each time the cell divides due the end replication problem. That is, unless the cell expresses telomerase. Telomerase is a ribonucleoprotein complex (a complex containing protein and RNA) that can add back telomeric repeats. So what happens if telomerase isn't expressed? Well, after ~50 divisions the shortened telomeres induce a cellular state known as replicative senescence. Basically, the cell stops dividing. This is thought to be beneficial since it acts as a tumour protective mechanism by preventing uncontrolled cells from replicating too many times. However, it can also reduce the regenerative potential of tissues. Senescent cells accumulate with age. Moreover, a weak negative correlation is also seen between age and telomere length. For these reasons there is much interest in using telomere restoration strategies to target aging and for treatments people suffering with telomeropathies. But how would this be achieved and would it pose a cancer risk? In this video we will address these questions and provide the details of why telomeres shorten with age and how the length could be restored. TIMESTAMPS Intro - 00:00 Why telomeres shorten - 00:45 Telomerase - 03:20 Cellular senescence & Hayflick limit - 04:30 Aging link (organismal/mouse studies) - 06:00 Telomere restoration strategies - 08:15 REFERENCES Telomeres: history, health, and hallmarks of aging - https://doi.org/10.1016/j.cell.2020.1... Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells - https://doi.org/10.1016/j.stem.2020.0... Jaskelioff, M., Muller, F., Paik, JH. et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469, 102–106 (2011). https://doi.org/10.1038/nature09603 Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice - https://doi.org/10.1016/S0092-8674(00... Icons in intro; "https://www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com