Other Free Encyclopedias » Medicine Encyclopedia » Aging Healthy - Part 1 » Cellular Aging: Telomeres - Telomeres Are Chromosome Caps, Telomere Structure, Telomeres And Replication, Telomeres And Replicative Senescence, Telomeres And Premature Aging Syndromes

Cellular Aging: Telomeres - Telomeres, Genome Stability, And Cancer

chromosome cells instability short length

The hallmark of telomeres is their ability to confer stability on chromosome ends and prevent chromosome ends from activating the cellular surveillance mechanisms protecting cells from the deleterious effects of DNA breaks. Chromosomes with critically short telomeres become compromised in chromosome-end stability, and, because telomeres are generally shorter in tumors than in adjacent healthy tissue, it was suggested that telomere dysfunction could contribute to tumorigenesis by increasing genomic instability. In the short term, this genomic instability might promote tumor formation by allowing growth-advantageous mutations (i.e., mutations that permit cells to remain viable under conditions when, normally, the cells would die) to accumulate rapidly. However, this scenario requires that the cellular mechanism(s) that normally monitor telomere length and prevent cells with critically short telomeres from dividing be blocked. Under these conditions, cells with critically short telomeres would continue dividing. These cells would enter a period of extreme chromosomal instability. Eventually, however, such rampant genome instability might prove deleterious to tumor survival by generating mutations in genes that are essential for cellular survival. Thus, stabilization of the genome, perhaps through activation of telomerase, would have a selective advantage. Experiments carried out by the DePinho and Greider groups utilizing telomerase-deficient mice support the idea that transient telomere malfunction may promote tumorigenesis.

Figure 4 Summary of the link between telomere length, replicative senescence, and tumorigenesis. In the germ line, telomerase is active and telomere length is stable. In somatic cells, telomerase is not active. As a result, telomeres become shorter with each division until a critical length is reached and the cells undergo replicative senescence. If this process is bypassed through mutation of regulating proteins, the cells will continue to divide until telomere function is lost. This results in a period of genome instability, which possibly promotes tumorigenesis through hypermutation. Reactivation of telemorase permits maintenance of telomeric DNA conferring immortality and genome stabilization. SOURCE: Greider, Carol. ``Mammalian Telomere Dynamics: Healing, Fragmentation, Shortening, and Stabilization.'' Current Opinion in Genetics and Development 4 (1994): 203-211.

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about 3 years ago

Telomeres, Lysosomes, Mitochondria, Cancer and Iron. Telomeres (the specific DNA-protein structures) found at both ends of each chromosome, protect genome from nucleolytic degradation, unnecessary recombination, repair, and interchromosomal fusion. Telomere length decreases with age. Certain individuals may be born with shorter telomeres or may have genetic disorder leading to shorter telomeres. Telomeres are created by telomerases. Several studies indicate that shorter telomeres are a risk factor for cancer. Shorter telomeres can induce genomic instability. Telomerases (ribonucleoprotein enzymes) are reactivated in most cancerous immortalized cells. Lysosomal alterations are common in cancerous cells. Lysosomes control cell death at several levels. Defects in cellular iron metabolism can cause the Warburg effect. Many cancerous cells are considered immortal because telomerase activity and lysosomal alterations allows them to divide virtually forever. However, subsets of immortalized cells lack telomerase activity. Iron is an essential cellular nutrient that is critical for DNA synthesis (for many cellular processes). Ribonucleotide reductase is an iron-dependent enzyme that is required for DNA synthesis. Iron is so important that without it all life would cease to exist. In human cells, iron is an essential component of hundreds of proteins and enzymes. Heme is an iron-containing compound found in a number of biologically important molecules. Cytochromes are heme-containing (and iron-containing) compounds that have important roles in mitochondrial electron transport. Nonheme iron-containing enzymes are critical to energy metabolism. Iron Response Elements are short sequences of nucleotides found in the messenger RNA (mRNA). Several genetic disorders and all known human carcinogens may lead to pathological accumulation of iron in the cells. While iron is an essential mineral, it is potentially carcinogenic. The Father of Oncology (Vadim Shapoval) says that the presence of excessive iron inside cancerous cells can lead to telomere end-replication problems, lysosomal alterations, mitochondrial dysfunction (Warburg effect), DNA mutations, chromosomal abnormalities (deletions, duplications, inversions, ring formations, translocations), chromothripsis and mitotic catastrophes. Primary tumors always develop at body sites of excessive iron deposits. Surgery (ceramic blades), direct intratumoral injections of iron-deficiency agents (ceramic needles) and clinical iron-deficiency methods (special diets; accurate blood donations) can successfully beat inherited and spontaneous, inoperable and metastatic cancers. http://www.medicalnewstoday.com/opinions/180307 ; http://www.medicalnewstoday.com/opinions/180418 ; http://medicine.jrank.org/pages/283/Cellular-Aging-Telomeres-Telomeres-genome-stability-cancer.html ; Together We (Net Industries and its Licensors, Medical News Today and Vadim Shapoval) Will Beat Cancer