Secret to a Long Health Span
It is clear that infections, and especially chronic ones that are intracellular, lead to cellular senescence and eventually to biological aging of the individual. Senescence in one cell begets senescence in the other and the domino effect spreads around the body just like prions spread, if phagocytsis does not clear the defective cells. In fact, this is easily mediated by amyloids, if not by inflammatory mediators produced by senescent cells themselves.
Dealing with senescence has been most challenging from the medical point of view. However, advances in research are yielding fruits.
It has been found that senescent cells are produced due to mild stress that allows the cells to mount a chronic damage response, involving P53, HSP with protein misfolding response that includes protein folding, autophagy and some repair. It is only when autophagy is overwhelmed, that senescence sets in, in full gear. The cell stops growing.
Research has shown that senescent cells become resistant to death either by apoptosis, necroptosis or otherwise. Until fairly recenty, the process of senescence was thought to be irreversible. Research, however, has found that not can senescent cells revert to their old stem cell selves, but they can also progress to cancer cells when they lose the P53 cycle arrest signal from mutation or through an oncogenic stimulus drive that overrides the P53.
Findings about senescent cells are interesting and promising from a therapeutic perspective. Senescent cells have been found to be deficient in nucleotides, as they do not make them, so they cannot grow or proliferate. They use carbon monoxide to stay dormant as they are usually found in a non-perfused niche in connective tissue.
This state of affairs can be changed by perfusing an organ to supply nutrients, niacin(vit B3) and oxygen that will convert carbon monoxide(CO) to carbon dioxide, generate NADPH to reactivate nucleotide synthesis, produce SCFAs in the gut microbiome and nonezymically that upregulate genes and stem cells will be regenerated from senescent cells.Those that cannot be saved can then be killed with quercetin and fisetin, which are plant products found in fruits and vegetables that have been found to be senolytic(they kill senescent cells). They are anti-oxidant, anti-inflammatory flavonoid polyphenols. Carbon monoxide, due to hypoxia, interferes with the mitochondrial electron transport system, promotes free radical production, induces autophagy which employs glycolysis, effects less energy output and continuous repair(senescent cells fail to grow or thrive)
Curcumin promotes senolysis by activating autophagy, and so does vit D. It should be noted that too much autophagy can lead to senescence through free radical production. The flavonols(flavonoid polyphenols) tone it down and sustain autophagy that does not go out of control. Hence fisetin and quercetin are more effective and less toxic senolytics.
Dr, Oliver Verbe Birnso, MD.
Dealing with senescence has been most challenging from the medical point of view. However, advances in research are yielding fruits.
It has been found that senescent cells are produced due to mild stress that allows the cells to mount a chronic damage response, involving P53, HSP with protein misfolding response that includes protein folding, autophagy and some repair. It is only when autophagy is overwhelmed, that senescence sets in, in full gear. The cell stops growing.
Research has shown that senescent cells become resistant to death either by apoptosis, necroptosis or otherwise. Until fairly recenty, the process of senescence was thought to be irreversible. Research, however, has found that not can senescent cells revert to their old stem cell selves, but they can also progress to cancer cells when they lose the P53 cycle arrest signal from mutation or through an oncogenic stimulus drive that overrides the P53.
Findings about senescent cells are interesting and promising from a therapeutic perspective. Senescent cells have been found to be deficient in nucleotides, as they do not make them, so they cannot grow or proliferate. They use carbon monoxide to stay dormant as they are usually found in a non-perfused niche in connective tissue.
This state of affairs can be changed by perfusing an organ to supply nutrients, niacin(vit B3) and oxygen that will convert carbon monoxide(CO) to carbon dioxide, generate NADPH to reactivate nucleotide synthesis, produce SCFAs in the gut microbiome and nonezymically that upregulate genes and stem cells will be regenerated from senescent cells.Those that cannot be saved can then be killed with quercetin and fisetin, which are plant products found in fruits and vegetables that have been found to be senolytic(they kill senescent cells). They are anti-oxidant, anti-inflammatory flavonoid polyphenols. Carbon monoxide, due to hypoxia, interferes with the mitochondrial electron transport system, promotes free radical production, induces autophagy which employs glycolysis, effects less energy output and continuous repair(senescent cells fail to grow or thrive)
Curcumin promotes senolysis by activating autophagy, and so does vit D. It should be noted that too much autophagy can lead to senescence through free radical production. The flavonols(flavonoid polyphenols) tone it down and sustain autophagy that does not go out of control. Hence fisetin and quercetin are more effective and less toxic senolytics.
Dr, Oliver Verbe Birnso, MD.
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