Are Telomeres the Key to Aging and Cancer
There is mounting evidence for the existence of an important relationship between telomeres and telomerase and cellular aging and cancer. We review the present knowledge of telomeres and telomerase with special . and lung cancer, a correlation between decreasing telomere lengths and an. Recently, the importance of telomere maintenance in human stem cells .. An inverse correlation between age-adjusted telomere length and.
After a point of critical telomere shortening, telomerase might be reactivated to stabilize or elongate the telomeric DNA. Tumors with telomeres just as long as or even longer than in the original tissue seem to be rarer but have been described in some human malignant tissues, e. There are two possible explanations for this phenomenon: Either an activated telomerase has elongated the once-shortened telomeres back to former length, or the tumor cells have not yet undergone enough cell divisions to induce significant shortening of telomeres.
Low amounts of telomerase activity in normal human tissues were found only in hematopoietic progenitor cells and activated T- and B-lymphocytes 41 ; in germ cells, ovaries, and testes 42 ; and in physiologically regenerating epithelial cells Results from examinations of normal tissues and benign cancers as well as malignant primary and metastatic tumors permit several conclusions.
As in most normal tissues, telomerase activity is not expressed in somatic tissues adjacent to the tumor tissue. Accordingly, telomerase activity has proved to be a reliable marker for detecting tumor cells in resection margins. In benign and premalignant tumors, including breast fibrocystic disease and fibroadenomas, benign prostatic hyperplasia, colorectal adenomas, anaplastic astrocytomas, and benign meningiomas and leiomyomas, in general no telomerase activity was detected; however, it was found in malignant tumor stages 44 45 46 In this way, telomerase activity is associated with the acquisition of malignancy.
The detection of telomerase activity at preneoplastic or benign growth stages may signify disease progression and be of diagnostic value. For example, telomerase activity has been found in some cases of benign prostate hyperplasia and of benign giant tumors of the bone 45 48 —all tissues that may progress to malignant tumors.
As shown by Hiyama et al. Among samples obtained by fine-needle aspiration, 14 of 14 patients whose aspirates contained detectable telomerase activity, and who subsequently underwent surgery, were confirmed to have breast cancer. Certain tumor types, such as neuroblastoma, display a lower telomerase activity in early-stage cancers, whereas expression in late-stage cases is higher Neuroblastomas of a special stage stage IVwhich had short telomeres and no or weak telomerase activity, tended to regress spontaneously 49 —possible proof of a correlation between an enzyme activity too weak to remain in an immortal tumor status and a favorable outcome for the patient.
Another example of telomerase activity in cancer diagnosis and as a prognostic indicator of clinical outcome is the results found in gastric cancers. Although a reliable tumor marker, telomerase activity is not an all-or-none phenomenon. To understand the regulation of telomerase during tumorigenesis, Greider et al.
The overhang at the lagging strand end of the chromosome is due to incomplete end replication see figure above.
Proteins associated with the telomere ends also help protect them and prevent them from triggering DNA repair pathways. The repeats that make up a telomere are eaten away slowly over many division cycles, providing a buffer that protects the internal chromosome regions bearing the genes at least, for some period of time.
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Telomere shortening has been connected to the aging of cells, and the progressive loss of telomeres may explain why cells can only divide a certain number of times 4 4. Telomerase Some cells have the ability to reverse telomere shortening by expressing telomerase, an enzyme that extends the telomeres of chromosomes. How does telomerase work? The enzyme binds to a special RNA molecule that contains a sequence complementary to the telomeric repeat. The primer may not be positioned right at the chromosome end and cannot be replaced with DNA, so an overhang will still be present.
However, the overall length of the telomere will be greater. Interestingly, many cancer cells have shortened telomeres, and telomerase is active in these cells. Before a cell can divide, it makes copies of its chromosomes so that both new cells will have identical genetic material. To be copied, a chromosome's two DNA strands must unwind and separate. An enzyme DNA polymerase then reads the existing strands to build two new strands.
It begins the process with the help of short pieces of RNA. When each new matching strand is complete, it is a bit shorter than the original strand because of the room needed at the end for this small piece of RNA.
It is like someone who paints himself into a corner and cannot paint the corner. Telomerase counteracts telomere shortening An enzyme named telomerase adds bases to the ends of telomeres.
Whats the difference between telomeres and telomerase | Naked Science Forum
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.
Structure of the catalytic subunit of telomerase, TERT. Telomeres and cancer As a cell begins to become cancerous, it divides more often, and its telomeres become very short. If its telomeres get too short, the cell may die. Often times, these cells escape death by making more telomerase enzyme, which prevents the telomeres from getting even shorter. Many cancers have shortened telomeres, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck. Measuring telomerase may be a way to detect cancer.
And if scientists can learn how to stop telomerase, they might be able to fight cancer by making cancer cells age and die.
In one experiment, researchers blocked telomerase activity in human breast and prostate cancer cells growing in the laboratory, prompting the tumor cells to die. But there are risks.
Telomeres and telomerase (article) | Khan Academy
Blocking telomerase could impair fertility, wound healing, and production of blood cells and immune system cells. Telomeres and aging Geneticist Richard Cawthon and colleagues at the University of Utah found shorter telomeres are associated with shorter lives.
Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease. If telomerase makes cancer cells immortal, could it prevent normal cells from aging?
Telomere and telomerase in stem cells
Could we extend lifespan by preserving or restoring the length of telomeres with telomerase? If so, would that increase our risk of getting cancer?
Scientists are not yet sure.A full explanation about the Telomerase and the end replication problem
But they have been able to use telomerase in the lab to keep human cells dividing far beyond their normal limit, and the cells do not become cancerous.