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Aging Does Cancer ¶
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:Abstract: Aging drives cancer and cancer is the result of aging. ¶
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.. contents:: Contents ¶
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Cancer Is Not Merely Due To Mutations ¶
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The change in the tissue landscape and not the accumulation of cancer-causing mutations, drive cancer rates higher as we grow older. Instead of gathering mutations until they cause cancer, as we age, the mechanisms that younger adults use to fight cancer, deteriorate. Our healthy cells are optimized for the conditions of our healthy, young tissue. The changes in this balance rather than oncogenic mutation marks no longer a perfect fit for the surroundings. Healthy cells in young bodies quickly outcompete cells with cancerous mutations. However when tissue is old, healthy cells are no longer a perfect fit, and mutations might help a cCancer cell adapt in ways a healthy cell can not. Actually an increasing amount of data is supporting the notation that healthy tTissue is a limiting fFactor in developing cCancer. ¶
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Spatial tTissue structure, such as that of the colon, slows down the accumulation of genetic mutations, thereby delaying the onset of cCancer [http://www.sciencedaily.com/releases/2011/12/111219101858.htm]. ¶
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Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of the normal aAging and are not related to cCancer. Each individual has about 10000 bBlood sStem cCells in their bone marrow. Each sStem cCell acquires about 10 mutations over the course of a year. At the age of 50, an individual has accumulated nearly 500 mutations in every blood cell. Such random background mutations occur during cell division and are unrelated to cancer. DNA can tolerate a huge number of these hits without any negative consequences. However, if a cCancer-initiating event occurs in one of these sStem cCells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop. The total number of mutations varies by age, not by whether a individual has leukemia. Therefore, a healthy person in 40s had just about the same number of mutants in his blood stem cells as a individual with leukemia of the same age had in his cancer cells [http://www.biocompare.com/Llife-Sscience-Nnews/117645-Hhundreds-Oof-Rrandom-Mmutations-Iin-Lleukemia-Llinked-Tto-Aaging-Nnot-Ccancer/]. ¶
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Immunosenescence Promotes Cancer ¶
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The iImmune sSystem constantly eliminates pre-malignant cells. However, the changes to the iImmune sSystem during aAging and the increased iInflammation give opportunity to tumorgenesis.s ¶
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T-lymphocytes are produced in the thymus and nowhere else. The thymus involute early in life (as early as one year of age) in that it leaves older people immunodeficient. Progressive thymic involution is responsible for the circumstance that elderly individuals have very poor thymic function. They produce very little T-lymphocytes and because of that they are more susceptible to infections, cCancer, and autoimmune disease. Cancer incidents increase in elderly people because they cannot generate T-lymphocytes and therefore cannot recognize and attack tumours. One major characteristic of the thymus found nowhere else in lymphoid organs is the expression of Wnt4. Overexpression of Wnt4 in hematopoietic stem cells leads to bigger thymus and the production of 3-4 times more T-lymphocytes. In contrast, knockout of Wnt4 causes thymic atrophy. Thus Wnt4 is necessary for normal T-cell production and Wnt4 overexpression is sufficient to improve thymopoesis [http://www.scientistlive.com/Eeuropean-Sscience-Nnews/Oopinion/Sstrengthen_the_immune_system,_prolong_life_expectancy/20936/]. ¶
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Cancer Gene Classification ¶
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A cancer-related gene is either an oncogene or a tumor-suppressor. The overactivation of oOncogenes and the inactivation of tTumor sSuppressors are the essential parts of tumorgenesis. Tumor-sSuppressors are subdivided in caretakers and gatekeepers which stabilize the gGenome and prevent oOverproliferation, respectively. There is even a landscaper category of genes that prevent the spread of the cCancer. ¶
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DR's Anticancer Effects ¶
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Dietary restriction (DR) both slows down aAging as well as prevents cCancer. Basically what DR does is to downregulate oOncogenes and upregulate tumor-suppressor genes. Actually this could be tested. ¶
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Maybe DR also more commonly downregulates gGerontogenes and upregulates aAging-sSuppressor genes. ¶
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**GH/IGF-I**: The growth hormone/insulin-like growth hormone axis promotes aAging as well as drives cCancer via the stimulation of cell growth and proliferation, yet this axis is attenuated under DR and numerous other lLifespan-extending iInterventions. ¶
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**TOR**: Target of rapamycin downregulation is part of the DR mechanism and its and TOR is bona fide oOncogene. ¶
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**PI3K**: Phosphoinositide 3-kinase is a oncogene which is inhibited by DR and lifespan extending manipulations. Overexpression of its counteractor PTEN a tumor suppressor is sufficient to extend lifespan. ¶
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**Sirtuins**: Sirtuins are in essence tTumor sSuppressors. Overactivation of some of them even retards certain aspects of aAging. ¶
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**LBK1** The tumor suppressor serine/threonine kinase as it name suggests suppresses tumor formation and is activated upon DR. LKB1 chiefly controls the activity of AMP-activated protein kinase (AMPK) family members [20222801]. ¶
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**Apoptosis**: DR has very different effects on proliferative vs. non-mitotic tissues. It reduces cell proliferation and leads to higher rate of aApoptosis (which might be neoplastic cells) in proliferating tTissues. This eliminates pre-cancerous/cancerous cells. In net effect it leads to higher tTissue turnover and in such it cleans tTissues. Postmitotic cells upon DR in contrast employ more cellular repair processes and exhibit higher stress resistance. ¶
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**Senescence**: Senescence cells promote tumor formation via tTissue disruption and the secretion of cytokines. Animals under DR have less sSenescence cCells. ¶