A Novel Method of Telomere Extension
Telomeres are the protective caps of repeated DNA sequences found at the end of chromosomes. Telomere length is a part of the regulatory system that prevents cells from dividing indefinitely: a little length is lost with each cell division, and a cell destroys itself or otherwise ceases to divide when its telomeres become too short. In stem cell populations, responsible for delivering fresh batches of long-telomere daughter cells into tissues to replace those lost due to reaching the limits of replication, the enzyme telomerase is active to maintain lengthy telomeres by adding extra repeating sequences to the ends. Cancer cells also make use of telomerase or other methods of lengthening telomeres in order to maintain their ability to rapidly and continually divide, but this process isn't normally active in the majority of the cells in the body. Average telomere length in white blood cells tends to decrease with age and illness, and this is really a proxy measure that blurs some combination of cell division rates and stem cell activity.
Researchers have lengthened healthy life in mice by boosting the activity of telomerase via genetic engineering, though it is still the case that there is no definitive experiment to show which of the possible mechanisms causes this life extension. Is it a matter of more stem cell activity, some secondary effect of having long telomeres such as increased cell life span, or another aspect of telomerase, such as its influence on mitochondrial biology? There is considerable interest in the research community in continuing to explore what might happen when telomeres are lengthened, and so it is inevitable that better methods of lengthening will be developed:
A new procedure can quickly and efficiently increase the length of human telomeres, the protective caps on the ends of chromosomes that are linked to aging and disease. The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases caused by shortened telomeres.The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell's protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase. Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.
The newly developed technique has an important advantage over other potential methods: It's temporary. The modified RNA is designed to reduce the cell's immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would. But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division. "We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase. Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious. In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent."