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telomeres implication for research, health, and lifespan
Cell Cycle Biology
patho midterm 1 function of telomerase in cancer cells
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Structures and Roles of Telomeres
Telomeres are essential structures in eukaryotic cells. Through repeat nucleotide sequencing of TTAGGG and their six associated protein complexes, they provide a “cap” over the rest of the chromosome, which protects the genetic material contained within the chromosome from instability1. Without the telomere structures, chromosomes are prone to tearing due to the action of nucleases and other damaging components within the nucleus. Torn chromosomes prove to be unstable, often fusing end-to-end or rearranging. The result can be catastrophic for the cell and eventually bring about cellular death.2 Consequently, telomeres are essential to cellular homeostasis.
In many cells, telomere length decreases with each replication. Because of this phenomenon, the cell has a limited number of divisions before apoptosis occurs. The number of divisions a cell can undergo before apoptosis ensues is known as the Hayflick limit3. The Hayflick limit states that there are about 50 generations of cellular division within each cell before cellular proliferation ceases due to apoptosis3. Therefore, telomere length has a direct correlation to how many times a cell divides. Once the telomeres are too short to protect the rest of the chromosome, degradation can occur. This creates a barrier to cellular immortality. Telomerase can help remove that barrier by its reverse transcriptase action4.
Composition and Function of Telomerase
Telomerase is a ribonucleoprotein DNA polymerase that catalyzes the lengthening of DNA on telomeres5. It accomplishes this by adding repetitive sequences of nucleic acid that are abundant in guanine2. Human telomerase consists of two major complexes, one being human telomerase reverse ...
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...Bache Nicolai. Robinson Phillip J. Reddel Roger R. Protein composition of catalytically active human telomerase from immortal cells. Science 2007:352:1850-1853.
7Mason Mark. Schuller Anthony. Skordalakes Emmanuel. Telomerase structure function. Current Opinion in Structural Biolog. 2011:21(1):92-100.
8Friedman K L. Cech TR. Essential functions of amino terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants. Genes Dev. 1999:13(21):2863-2874.
9Hengesbach Martin. Akiyama Benjamin M. Stone Michael D. Single-molecule analysis of telomerase function and structure. Current Opinion in Structural Biology. 2011:15(6):845-852.
10Podlevsky Joshua D. Chen Julian. It all comes together at the ends: Telomerase structure, function and biogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2012:730(1-2):3-11.
Miller, Kenneth R. and Joseph S. Levine. “Chapter 12: DNA and RNA.” Biology. Upper Saddle River: Pearson Education, Inc., 2002. Print.
Inside the nucleus of our cells, our genes are on double-stranded molecules of DNA called chromosomes. At the top and bottom of the chromosomes are fragments of DNA known as Telomeres which defend our genes, give us the ability for our cells to divide, and hold secrets to how we age and how we get cancer. Telomeres are like the ends of shoelaces (because they keep the chromosomes’ ends from fraying). But when a cell divides, the Telomere gets smaller and shorter. When they get too short, the cell can’t divide. The Telomeres then become “senescent” or inactive. This shortening is linked with aging, cancer, and death-risk. Telomeres should also be compared to a bomb fuse. Without Telomeres, the main part of the chromosome would get smaller whenever the cell divides. This can cause a malfunction or cancer. An enzyme named telomerase adds bases to the ends of Telomeres. In young cells, telomerase keeps Telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the Telomeres grow shorter and the cells age. Telomerase remains active in sperm and eggs, which are passed from one generation to the next. If reproductive cells did not have telomerase to maintain the length of their Telomeres, any organism with such cells would soon go extinct.
9. Travis, John. "End games: tips of chromosomes may contain secrets of cancer and aging." Science News 25 Nov. 1995: 362+. Science in Context. Web. 20 May 2014.
Hall, Linley Erin. “Understanding Genetics DNA and RNA.” New York: The Rosen Publishing Group, Inc., 2011. Print. 01 Apr. 2014.
Progeria occurs because there is a mutation in LMNA, a gene that produces specific protein, lamin A protein, that plays an integral role in holding a cell’s nucleus together. This mutation leads to the production of progerin, a protein that causes the nucleus to be unstable. With this instability comes “the process of premature aging and disease in Progeria.(1)” The accumulation of the protein Progerin also affects telomeres, proteins that contribute to the aging process of cells and leads to telomere disfunction.
Humans undergo several stages during their lifetime including growth, development, reproduction and senescence. Senescence is defined as the deteriorative biological changes that organisms experience as they age eventually leading to death. These changes include low metabolism, a weak immune system, memory loss, poor vision and loss of hearing. Senescence begins in humans during their post-reproductive years. However, gerontology research has shown that individuals who reproduce late have longer life spans compared to individuals who reproduce early. Nonetheless, it does not indicate that senescence is inevitable. All organisms experience senescence, but at different rates and time. Many genetic diseases such as Alzheimer’s disease and Huntington’s disease are prevalent in older individuals and the symptoms being to appear in middle adulthood. The causes of genetic diseases and disabilities in older individuals are explained by three evolutionary theories: antagonistic pleiotropy theory, mutation accumulation theory and disposable soma theory. These theories suggest that favorable natural selection and heavy allocation of resources for somatic maintenance during the reproductive period decreases the chances of genetic diseases in younger individuals.
3. Corey, E. J., Barbara Czako, and Laszlo Kurti. Molecules and medicine. New Jersey: John
DNA Timeline: DNA Science from Mendel to Today. (2014). Retrieved May 29, 2014, from http://www.dnai.org/timeline/
doi:http://dx.doi.org/10.1007/s00424-009-0728-1 Tümpel, S., & Rudolph, K. (2012). The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Annals of the New York Academy of Sciences,1266(1), 28-39. doi:10.1111/j.1749-6632.2012.06547.x Yang, Q. (2009).
'Telomere at senescence' A chromosome of an adult cell with the telomere labeled 'Telomere shortens after multiple replications' In 1961, Leonard Hayflick and Paul Moorhead made an astonishing discovery that human cells originating from embryonic tissues could only divide a limited number of times in culture, known as the Hayflick Limit.2 This is called cellular senescence and eventually leads to cell death. According to the National Institute of Aging (NIA),3 “DNA damage build-up occurs when a cell divides and passes its genetic information on to its two daughter cells. Telomeres shorten each time a cell divides. In most cells, the telomeres eventually reach a critical length when the cell stops proliferation and become senescent.” Due to Hayflick and Moorhead’s research, it was found that the telomeres, which are located at the ends of DNA, become shorter as...
Rose, Michael R., Molly K. Burke, Parvin Shahrestani, and Laurence D. Mueller. "Evolution of ageing since Darwin." Journal of Genetics 87.4 (2008): 363-371. Print.
Telomeres power the successful reproduction and division of cells, and are found in the DNA (deoxyribonucleic acid) of genes found in chromosomes. When she was tested, it was discovered that her telomeres were shorter than other non-cloned sheep her age. However, scientists say that this mistake could be useful for treatment of cancer. By giving cancer cells in the body short telomeres and putting them back into the body, other cancer cells would be infected, and would die qui...
The scientific and medical progress of DNA as been emense, from involving the identification of our genes that trigger major diseases or the creation and manufacture of drugs to treat these diseases. DNA has many significant uses to society, health and culture of today. One important area of DNA research is that used for genetic and medical research. Our abi...
As medical and scientific equipment begins to evolve, many interesting discoveries have been made over decades of meticulous research. These discoveries enable scientists to build on their knowledge and come up with the theories that they do. For example, the discovery of telomeres was a monumental step forward in this field. Telomeres are protective structures on the ends of DNA strands. These structures gradually shorten to a point where the...
Throughout history, mankind has been obsessed with discovering a cure for any ailments or disorders that could disrupt or hinder their short lives, especially those to evade the aging process. With society becoming increasingly interested in everlasting beauty and living longer, the race to discover the main contributor toward aging begun in the early nineteen hundreds. In the midst of this quest, several biological theories had been developed. Among these theories is the immunity or immunological theory. This paper will discuss the immunological theory of aging by explaining the theory, giving a history of its origin and a description of further development within the evolution of the theory.