Telomere Shortening.....

Microbiol Mol Biol Rev 2002 Sep;66(3):407-25, table of contents Related Articles, LinksHuman telomerase and its regulation.Cong YS, Wright WE, Shay JW.Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA. Yu-Sheng.Cong@UTSouthwestern.eduThe telomere is a special functional complex at the end of linear eukaryotic chromosomes, consisting of tandem repeat DNA sequences and associated proteins. It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. The synthesis of telomeres is mainly achieved by the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase that adds telomeric DNA to telomeres. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. In humans, telomerase activity is tightly regulated during development and oncogenesis. The modulation of telomerase activity may therefore have important implications in antiaging and anticancer therapy. This review describes the currently known components of the telomerase complex and attempts to provide an update on the molecular mechanisms of human telomerase regulation.

Dolly was cloned from an adult somatic cell. The nucleus was injected into an oocyte that was enucleated. It was then zapped with electricity to mimic the voltage change induced by fertilization when sperm penetrates the cell membrane (may be wrong on specifics since I studied repro biol about 15 years ago). Thus the telomeres of Dolly never had the chance to go through the maintanance process that would normally occur during oogenesis or spermatogenesis. If you clone a clone that already starts with chromosomes that are degraded i.e. take cells from Dolly right before she was euthanized and make clones they will start with an even shorter set of telomeres than Dolly had...keep re-iterating the process and soon you won't get viable clones.If you want imortality (or at least to slow aging down) you need to control telomerase activity to maintain the chromosome ends, not just add to them uncontrolled. Otherwise, expect to have a nice constellation of cancer types in short order.

Thanks for the references WK. Ease of cloning itself seems to be highly variable i.e. mice are easy but cats and dogs are more difficult. I am also not yet convinced that the telomere hypothesis of aging really plays such a causative role as some of its proponents suggest. Of course if the telomeres shorten to the point of knocking out genes that would be sub optimal. But does this happen in every cell? In enough cells to make a difference? Is it more importatn than loss of mtDNA function with age? Accumulation of DNA damage from exposure to oxygen radicals over time? However, it is interesting that telomerase can re-activate in some cancers suggesting a dedifferentiation of the specified cell types and re starting of the developmental process (at least in part).I only have a minor side interest in cloning that derives from having had to debate groups that claimed mammoths would be cloned out of extinction from DNA extracted from fossils...which is pure nonsense.
Otherwise, I will just read whatever Ian Wilmut writes