Telomerase at the intersection of cancer and aging - 0 views
www.ncbi.nlm.nih.gov/...PMC3896987
telomere telomeres telomerase telomerase activator aging disease cancer
shared by Nathan Goodyear on 18 May 16
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The anti-aging role of telomerase has been demonstrated to be largely mediated by its canonical role in elongating telomeres, which prevents the accumulation of critically short telomeres and loss of tissue homeostasis
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increased abundance of short telomeres correlates with higher genomic instability and decreased longevity in various organisms, including mice, zebrafish, and yeast
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mice deficient for telomerase or for telomere binding proteins are characterized by accelerated age-related defects
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In humans, short telomeres are considered good indicators of an individual’s health status and correlate with both genetic and environmental factors
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Although recent findings strongly support the idea that short telomeres drive several age-related diseases 38 we cannot exclude the possibility that in some situations short telomeres may be a consequence of the disease itself.
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the current view is that telomerase deficiency may contribute to the early steps of cancer development by fueling chromosomal instability, while subsequent activation of telomerase may be necessary to allow tumor growth and tumor progression towards more malignant states
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telomerase can stimulate tumor progression by ensuring maintenance of telomeres above a critically short length, thus preventing induction of cellular senescence or apoptosis
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Almost all human cancers present activation of telomerase as a hallmark, most likely as a mechanism to allow unlimited cell proliferation of tumor cells
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recent evidence demonstrated that short telomeres alone could lead to genomic instability and cancer
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Getting rid of telomerase can also be problematic; the lack of telomerase could lead to increased chromosomal instability, which in turn could be at the basis for cancer initiation when tumor suppressor barriers are bypassed
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telomerase activation in adult or old mice by means of a gene therapy strategy was shown to be sufficient to improve metabolic fitness, neuromuscular capacity, and prevent bone loss, as well as significantly increase both median and maximum longevity, without increased cancer incidence
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These studies suggest that telomerase expression could be considered a feasible approach to reverse tissue dysfunction and extend healthy lifespan without increasing cancer incidence
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a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging
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Telomerase expression in a background of high levels of tumor suppressors or in aged organisms seems to prevent its expected pro-cancer activity and yet it still functions as an anti-aging factor
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Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging. In contrast, Telomerase activity is found to be involved in carcinogenesis. Increased carcinogenic potential of Telomerase activity has not borne out in studies. In addition, increased CD8 cell activity as a result of Telomerase activation will actually decrease carcinogenic potential via NK activation.