Friday, March 13, 2015

Age-Related Condition and Disease Therapy With Telomere Extension

     Can modern medicine eventually actually allow people to live forever? This is a question that still has no answer, but maybe is one step closer to being answered. In a recent study published in the FASEB journal, researchers have discovered how to extend telomeres in cells and increase the length of time they remain able to proliferate without mutation.

     Telomeres are short repeated segments thaw work together with various proteins to protect the ends of important DNA from becoming damaged. These sequences do not code for anything important, so they are essentially disposable by the cells. Overtime, the telomeres shorten with each division, as well as for other reasons and eventually they become too short to protect the DNA anymore. When this happens, pathways in the cell caused by senescence that prevent mutation take over and force the cell to die through apoptosis. Normal humans have many years before their telomeres shorten to a deleterious point, generally marked by the onset of age-related disease and ailments. However, those born with diseases like Duchenne Muscular Dystrophy have extremely short telomeres and their cells are only able to divide a few times before the tissue severely deteriorates and senesces. 

     A research team has found a way to artificially lengthen the telomeres of a cell using a modified TERT mRNA, which is involved in telomerase, or the protein that lengthens telomeres in stem cells, activity. They tested this new mRNA in fetal lung fibroblast cells and 30 year old skeletal myoblasts, both of which are cell types that generally senesce quickly. Cells were treated either once, twice, or three separate times in order to measure the effectiveness and risks of multiple doses, and each dose was found to successfully increase telomere length. Overall, treated cells were found to have a ten-fold increase in cell number in culture versus those not treated with the TERT mRNA. This integral treatment passes through the cell quickly and does not linger, but still effectively extends the telomere length noticeably. 

     This new method also avoids several risks that come with increase telomerase activity, the largest of which is cell immortalization, which leads to tumor growth. The results showed that at cell type increased significantly for a time, but their growth curves leveled off to that of a normal cell, suggesting that they are not immortal. The reason for this is the brevity of the action of the telomerase as well as the fact that the modified TERT mRNA does not integrate with the genome, so once it has been used it no longer function and the cell returns to its normal state, just with longer telomeres, and do eventually show signs of senescence.
     This new discovery could possibly hold many benefits for people if it reaches the stage of therapeutic use. It could help those with telomere linked diseases such as Duchenne Muscular Dystrophy because it represents a novel new treatment method to fix the problem DMD patients suffer from directly. Since their telomeres are short to begin with and their muscle tissue degrades rapidly, this treatment could help to rapidly extend their telomere length and give cells ten more years of healthy proliferation with each dose of treatment. Also, it could help with roadblocks in regenerative medicine such as not having enough of the desired cell type, like stem cells, and having them die in culture before they can be used in treatment. With lengthened telomeres, these cells could proliferate much more and provide the numbers that are needed for more efficient and effective regenerative medicine techniques. Along with this, the telomere extension also holds promise for being able to relieve age-related illness and ailments that come from cell senescence as the telomeres shorten. If the telomeres in the cells of the part of the body that is degrading are lengthened, it would allow for the body to possibly recover from the disease or ailment caused by the senescence of cells as the body ages. The brevity of the treatment’s action in cells makes it the most viable and valuable form of telomere extension yet discovered and although the therapeutic uses for it have yet to be tested, this discovery holds exciting promise for the future through all of its possible applications. 


Future Timeline:

Ramunas, John, et al. "Transient Delivery of Modified mRNA Encoding TERT Rapidly Extends Telomeres in Human Cells." The FASEB Journal.January (2015)Print.


  1. Reading about technologies like the one that you discuss reminds me how careful the scientific community needs to be in the way it presents new technologies that some people might see as ethically problematic. Once words like "immortality" start getting thrown around, real impediments to further scientific progress can be thrown up by the non-scientists who make our laws. Existing within a conservative American culture, the scientific community needs to frame dialogues in a way that will survive scrutiny by men and women who are suspicious of efforts to address problems with fundamental life processes.

    1. I agree with Joe. I think this topic is very interesting and could have many medicinal applications that could change the way many diseases are being treated currently. However, scientific research also comes with an ethical component and presenting ideas such as "immortality" or similarly with the crispr/cas system the idea of "modifying the human genome" can pose potentially problems to the scientific community. Because not everyone understands the level of complexity behind these ideas and that these ideas are still in the works, the way information is presented should not jump to any conclusions that are not necessarily true.

  2. I could imagine a lot ethical issues stemming from the abuse of this type of technology, and I believe that there would need to be many regulations and screenings, both physical and psychological, before a person would be accepted to use this therapy for real. I think that people would maybe try to use it for age reversal/rejuvenation, similar to how plastic surgery is used today. However, it is definitely an exciting idea and I could see it being a great alternative for people with telomere-linked diseases.