Thursday, May 10, 2012

The Tricks of Telomeres, Aging, and Cancer

http://www.johnfegy.com/
I found an article in Nature that talks about how telomerase activation could be a potential valuable therapy to treat some disorders characterized by premature aging, and even offer the possibility of slowing down the normal aging process by reawakening telomerase. However, this article introduces the reactivation of telomerase as a potentially harmful process that could instigate the occurrence of cancer. The article serves as a great initial tool to understand the link between telomeres, aging, cancer, and the many difficulties of why the relationship among these three is highly misunderstood. After all, it is difficult to understand how telomeres can have such contradictory connotations - as a  revolutionary therapy against aging diseases, and on the other hand, being part of the major six hallmarks of cancer by enabling replicative immortality. 

The purpose of this blog is to illustrate why the views on telomeres posses such a contradictory nature, and why it seems unlikely to view them only as cancerous agents or therapeutic tools.  However, in case a refresher is needed as to what telomeres are, please direct your attention to this short video.

The idea that telomere activation could be the foundation of developing a technique that relieves premature aging, and even halts the normal process of aging to some degree is based on a study performed by a group of scientists that found the reactivation of telomeres to be capable of reversing degenerated tissue in aged mice deficient in telomeres. In this study the reactivation of telomeres was done by engineering mice in which inactivated telomeres could be switched to active by administering a chemical  called 4-OHT.  This chemicall has the faculties to allow telomeres to be turned on and off. Thus, allowing to see the effect the reactivation of telomeres has on mice by comparing tissue before and after it was treated. 

From this study it was determined that activating telomeres in mice who did not have previous cell activity and were affected by aged related disorders reduced DNA damage signalling and associated cellular checkpoint responses, allow the re-entry of cells into the cell cycle, reduced apoptosis of tested germ cells and intestinal crypt cells, eliminated degenerative phenotypes across multiple organs such as testes, spleens, and intestines, improved neurogenesis in the brain, alleviated myelin levels in neurons, increased repopulation of white matter structure, as well as other positive side effects of reactivation. 



a) Haemotoxylin and eosin-stained section of testes. b) Splenocytes stained.    
c) small intestine sections. d) Tested weights of adult males. e) nuclear foci per 
100. f) nuclear foci per 100 crypts.g) Litter size. h) spleen weight. i) Apoptotic
cells per 100 intestinal crypts. G0 represent cells with intact telomerase, G4 
cellsdeficient in telomerase, and vehicle represents control treatment. Open
bars have not 4-OHT, close bars have 4-OHT. 
This figure represents the extent that telomerase reactivation  has on damaged organs affected by the deficit of telomeres. In this illustration, it can bee seen that damaged cells from the testes, spleen, and intestinal crypts show a significant improvement in the presence of  4-OHT in comparison to when telomerase was inactive. Cells with intact telomeres are represented as G0 and those that are labeled as G4 posses dysfunctional telomeres.  Results show that treatment rejuvenation was seen despite an entrenched degenerative state by the incidents of reduction of apoptosis in cell testes and intestinal crypts, decrease of instances atrophy with restoration in normal testes and spleen size, and increase fecundity. Interestingly, however, in this study, and as represented in this figure, cells whose telomerase were intact did not show much effect when 4-OHT. This could suggest that unlike how the Nature article believe that reactivation of telomeres could improve or halt the normal parameter of aging, there is not effect to cells that have functional telomeres. Thus, telomeres might serve as a therapeutic approach to improve premature age associated diseases, but not as an enhancer to rejuvenate cells to an abnormal condition. 


This article serves as a powerful tool to understand the  extent of the effects that telomerase has on maintaining the stability and integrity of our genome, yet this study fails to address the consequences that  reactivating telomerase could have in the long run. The fate of the mice in the study is not known; it could be possible that the rejuvenation of the cells was followed by cancerous circumstances. After all, cancer formation can be possible if cancerous cells acquire the mechanism to restore and stabilize telomerase to avoid death. In addition, as it was discussed in class, when telomeres are disrupted the DNA damage produces a fueled chain reaction that increases the change of incidents of cell formation as more biological paths are disrupted. For more information about how telomeres cause cancer please direct your attention to this blog (this blog is in the making...so please be patient).