Studies Of Caloric Restriction, Resveratrol And Sirt1 Demonstrate A ?Metabotype’ Continuum From Cellular Rejuvenation To Aging To Cancer
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thousand mitochondrial genomes that might be coupled to some selection process, maybe based upon some kind of selection for fidelity of consensus sequence. It seems obvious that there must be some kind selective renewal system, because mitochondria pass from generation to generation via oogenesis, on average, without a single point mutation. Without such a process, it would not take many generations for eggs to contain a gibberish of mitochondrial sequences, rendering the following of the matrilineal line to a virtual impossibility. The fact that we can follow the matrilineal line through thousands of generations, supports this notion. I envision something like a polytene chromosomal sequence comparator mechanism of some kind, or perhaps, a highly protected and sequestered mitochondrial ‘mother genome’ somewhere in the cell. Evidence for real biogenesis mounts. In adult body cells, mitochondria progressively degenerate into inefficient couplers of hydrogen, electrons and oxygen to ATP and water production. And not just one thing, but a host of things go wrong with mitochondria as adult cells age, with one of the hottest causal suspects being ROS mediated mutagenesis. Concomitant with reduced mitochondrial efficiency over time, is an increase in glycolytic ATP production. Thus, as cells age, the anaerobic to aerobic ATP production ratio rises, and begins to appear more like the pattern seen in cancer cells. Since most adult cells are terminally differentiated, and can no longer divide, such a ratio shift does not pose a cancer risk, as would adult stem cells, which still have functional telomeres, and could possibly become telomerase immortalized. Telomere shortening to terminal differentiation is a well established mechanism, putatively, for avoiding cancerous progression in adult cells. However, non-terminally differentiated adult cells and adult stem cells can divide, and they generally divide to replace dead or missing adult tissue, under the directive of growth factors. Under such conditions, tissues are replaced but they are not rejuvenated. Instead of young dividing new cells replacing old dead cells, old dividing cells are replacing them, in part because mitochondrial biogenesis is not occurring. Cells are being replaced, but the tissue is not being rejuvenated. It appears that as we age, the metabolic phenotype (metabotype) of the aging cell operates more and more like a cancer cell metabotype. Somehow, it seems that that there is no great evolutionary pressure to put additional roadblocks to such a metabotype progression, especially with the, aforementioned, long list of non-metabolic quality assurance mechanisms already in the toolkit. In fact, such a progressive metabolic transition probably assists the evolutionary process. From an evolutionary perspective, it is preferred at a certain point to dispose of the old bodies, which represent yesterday’s genetic experiment, with the next generational gene mix experiment. After all, it is the genome that has a shot at perpetuity, and not the vehicles it employs to get there. In summary, it appears that adult tissues are aged metabotypes of juvenile tissues and adult stem cells are aged metabotypes of fetal stem cells, and that their metabotypes progress toward the cancer cell metabotype, irrespective of other components of the cancer cell transformational process. There appears to be a blended metabolic continuity between these basic temporal cell types, and recent science on cancer and aging are yielding insights that show metabolic crossover applications between these once disparate fields of research. It appears that we are beginning to achieve a degree of control over both aging and cancer, at least from a metabotype perspective.
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