After puberty, under ad libitum conditions, it becomes pretty clear that the SIRT1 system is, not only, not needed, but is not utilized, probably because it becomes disadvantageous in the statistical evolutionary survival sense. In the adult phase it, appears that cell senescence is an obligatory rule that can only be violated if survival of the next generation is at risk, due to the risk to the survival of the present generation, via starvation. Thus it does not matter if, under feast conditions, with procreation accomplished, that cancer becomes a natural outcome of declining metabolic efficiency, combined with the other required changes in cell growth control systems. In the adult system, inefficient catabolism diverts anabolic processes toward fat storage and pushes cells to become more dependant upon the cori cycle as they become more fuel dependant upon glucose by diverting excess pyruvate to lactic acid for export to the liver for gluconeogenesis. Such cells are metabotype ‘pre-adapted’ for cancer, as well as for organism aging or death, due to disrepair, because it really doesn’t matter how the organism is disposed of, as long as it is disposed of, usually by predation or disease, of course, due to its aged and weakened condition, Only under nutrient fuel paucity conditions does this natural decay process seem to be interrupted. The fact that SIRT gene knockout mice age rapidly and die very early, only underscores these conclusions.
SIRT1 up regulation has just the opposite effect. Mitochondrial biogenesis occurs, the metabotype reverts to a juvenile metabotype , adult life span lengthens, cancer incidence declines, regain of tissue function, such as that of muscle, liver, neurological etc. takes place and total organismal energy output efficiency and general vitality ensues. The fact that resveratrol mimics this general condition, is a most fortunate discovery. The fact that the pharmaceutical giants are at war over resveratrol and its caloric restriction mimetic capacities, shows just how far human folly can escalate when so many billions of dollars are at stake, especially if the leading candidate drug is unpatentable. Although the affinity chip data indicate that resveratrol bypasses SIRT one and IGF, the fact that it activates 99+% of its downstream cascade, in at least three tissue types, speaks volumes. The physiological and cytological studies, which support the rejuvenative effects, arise from too many sources for it to be a collusion, accident or folly.
Regardless, continued research on actual SIRT1 activators, resveratrol, its analogues or SIRT1 downstream cascade activators, these recent breakthroughs should spur a huge amount of basic research in both aging and cancer, and should, especially, reinvigorate a long overdue reinvestigation of the therapeutic efficacy of cancer cell intermediary metabolic interventions. This is particularly true, in light of the preliminary results from the employment of DCA, and the pivotal position between glycolysis and the mitochondrion occupied by pyruvic acid.
At the present time, the list of anti-aging supplements that need to be taken to ward off the plethora of cell systems in decline in aging organisms, is mammoth, to put it lightly. Many of these supplements (but, by no means all, such as, vitamins, anti-oxidants, phytonutrients etc.) are provided abundantly by juvenile cells, but are produced in progressively lessening quantities by aging organs, tissues and cells. However, by turning on a SIRT1 rejuvenation gene cascade, it appears that life extension occurs in the absence of such supplementation. This fact alone has incredible implications, because it proves that the vast majority of youthful cell vigor information, remains intact, and is recoverable with the right inducement(s). The implications are gargantuan, because it declares with a delightful certainty, that normal aging is not, so much so, a process of irreversible decay, as it is a form of highly controlled preplanned obsolescence. The investigation of modified supplementation, in tandem with rejuvenation gene cascade initiation and mitochondrial biogenesis control systems, could offer a fertile field for the cultivation of a broad area of applications. It is becoming progressively more clear that glycolytic and mitochondrial catabolic control systems, in and of themselves, have deep impacts upon cellular function, outside the governance of cell growth control signaling pathways. The notion that such a system has, at its roots, control over such sweeping concepts, as aging, biogenesis, rejuvenation and cancer, is almost stupefying. After all, these systems, and their core control elements, predate multicellularity and the need for differential cell