Unfortunately, scientists are far from curing this universal "disease" known as aging. However, understanding the mechanisms of aging will have a more immediate impact on the development of stem cell therapies, and researchers at the University of Gothenburg in Sweden have discovered that the female egg is capable of reversing this telomere molecular clock.
In stem cell therapy, stem cells are introduced into areas of damaged tissue. To create healthy replacement tissue, somatic cell nuclei of the patient are inserted into undifferentiated cells (egg cells for example). These transformed cells now have the capacity to develop into any tissue type that the patient requires.
On paper, this approach to cure damaged tissue sounds "simple." But alas, since molecular biology is involved, surely we know better than to make such an assumption. Case in point: the telomere shortening problem.
Telomeres are specialized genetic structures at the very ends of chromosomes. Their primary function is to protect genes that are more internally located on chromosomes during replication. When cells complete replicating their genetic material, an enzyme called "telomerase" is recruited which is responsible for the production of telomeres. Unlike unicellular organisms, eukaryotes have a limited supply of telomerase and that supply is dependent on how many divisions the cell has previously gone through.
In prior research, telomere shortening has been shown to limit the life span of stem cells. Since telomere length is a function of age, transferring the aged nuclei of donors into undifferentiated cells to promote new tissue growth is recognized as a potentially serious problem. Therefore, establishing precisely how telomere length affects stem cell longevity is crucial in the development of therapeutic strategies.
The best evidence that supports the notion that telomeres have a direct role in organismal aging comes from studying diseases such as Werner Syndrome which is characterized by having an abnormally high rate of telomere attrition. In contrast, cancer cells are often found to have increased levels of telomerase which is believed to be partially responsible for their immortality.
As telomerase supplies deplete in normal cells, the cells become less efficient at sustaining optimal telomere length. Telomere attrition can cause abnormalities during cell division and even alter the expression of other genes that reside next to telomeres (this is known as the "telomere position effect").
Although there is a great deal of concern with decreasing stem cell life span as a consequence of introducing aged nuclei, researchers have discovered that egg cells are able to re-extend depleted telomeres, thus turning back the molecular clock.
"The genetic stability of the transplanted cells has been a serious concern until now, and it was feared that the life time of these cells would depend on the age of the cell nucleus that was transferred. Our results suggest that this is not the case," explains Associate Professor Tomas Simonsson.
It is well documented that the age of a mother is correlated with an increased risk for fetal genetic abnormalities. In other words, the age of a female's egg cell directly affects the health of a developing fetus. Males on the other hand, are fertile throughout life and their age does not reduce fetal health. However, this does not imply that male sperm nuclei are not susceptible to telomere aging. With these facts in mind, it was speculated that perhaps the female egg might actually extend sperm telomeres—the Swedish research team proved this.
"We are the first to show that egg cells have the ability to rejuvenate other cells, and this is an important result for future stem cell research," says Simonsoon.
The discovery that the egg cell can extend the telomeres of a fertilizing sperm cell is important because it can be used as an undifferentiated cell in stem cell therapy. Upon patient nuclei introduction, this research suggests that eggs cells have the potential to elongate aged telomeres.
To date, reprogrammed stem cells have only been used in animal experimentation. Although the telomere shortening problem may have been solved, more research is necessary considering other literature suggests that other known and possibly unknown variables also play a role in stem cell vitality.
Overall, it is only a matter of time before stem cell therapy becomes an available treatment option for diseases such as Parkinson's, Diabetes Type I and Muscular Dystrophy.
Blasco, M. A. (2007). Telomere length, stem cells and aging. Nature Chemical Biology 3(10):640-649.
Ljubuncic, P. and Reznick, A. Z. (2009). The evolutionary theories of aging revisited; a mini-review. Gerontology 55:205-216.
Marion, R. M., Strati, K., Li, H., Tejera, A., Schoeftner, S., Ortega, S., Serrano, M., Blasco, M. A. (2009). Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4:141-154.
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