Mitochondria and Health
Senescence is the hallmark of cellular aging. The senescent cells have stopped dividing. Cells accumulate mutations and structural damage with age. The damage is sensed and the cells are then taken out of the cell cycle by the tumor suppressor, p53, for autophagy and repairs or to undergo programmed cell death. In either case there is rejuvenation. There is, however, an intermediate scenario where, due to lack of the necessary resources, these cells become stuck in limbo. A brake is pulled on them and the cells shrivel due low growth or activity and fail to perform the normal biological function. They still occupy space and prevent the capable cells--stem or induced-stem--from dividing. They, however, begin to secrete inflammatory factors, instead.
Coupled to the renegade shriveled state, inflammation causes further structural damage in tissues and organs of the body, leading to degeneration. The common obvious signs are that the skin ages, the immune function plummets, the eyes and ears fail, the bowel function is impaired, the brain becomes less sharp and locomotion is impacted.
The mitochondrion, the powerhouse of the cell, is very much involved in events that lead to cellular senescence. For one thing, this organelle is the first target of damage due to its sensitivity and production of oxygen free radicals during the process of energy realization from food substrate. Endoplasmic stress and the resulting unfolding or misfolding of proteins will also damage the mitochondria--as well as other targets. Hence, an over-activated state will eventually lead to senescence, if no autophagic or apoptotic rescue operation steps in.
Clearly, autophagy and more importantly mitochondrial autophagy(mitophagy), rescues these cells, waiting in limbo. The untidy baggage is transported to lysosomes for degradation. This creates room and resources for new mitochondria to form to replace the old ones(turnover). Autophagy is not restricted to damaged tissue, when triggered by, say, diet restriction, the influence of glucagon or from exercise. It is regulated by PINK1 and Parkin protein.
Before autophagy salvage, there will have been some mitochondrial remodeling through fusion and fission and possibly cell death, and which is dependent on activity or some stress(metabolic or environmental like lactic acid buildup). Fusion allows the benefit from the healthy genes of one mitochondrion to compensate for the defect in a degenerate one. Some repair is possible. Eventually, with further stress, the situation becomes irremediable by this mechanism and cells become senescent. The defective mitochondria divide in the process of fission, if autophagy doesn't kick in, and this will lead to apoptosis. Alternatively, following some trigger, the brake is lifted off the genome with mutation to the p53 gene, and oncogenic drivers--growth factors(cytokines) and phosphorylation--will push the cell into a malignant cancer state.
A recent study found that a cell without mitochondria reverts to the juvenile stem state. Fewer but healthy mitochondria would mean low metabolism, less cellular stress and long life with the blessings of p53 or good immunity to pick the odd ones out(hence the long lifespan of the turtle). The study underscores the importance of autophagy in aging, disease, health and lifespan. Diet restriction, exercise, stress management, avoiding environmental toxins are measures to take to promote health. High metabolism followed by low, compromised metabolism and activity, resulting from unhealthy, defective mitochondria, will lead to inflammation, disease, obesity and aging, instead.
Dr. Oliver Verbe Birnso, MD.
Coupled to the renegade shriveled state, inflammation causes further structural damage in tissues and organs of the body, leading to degeneration. The common obvious signs are that the skin ages, the immune function plummets, the eyes and ears fail, the bowel function is impaired, the brain becomes less sharp and locomotion is impacted.
The mitochondrion, the powerhouse of the cell, is very much involved in events that lead to cellular senescence. For one thing, this organelle is the first target of damage due to its sensitivity and production of oxygen free radicals during the process of energy realization from food substrate. Endoplasmic stress and the resulting unfolding or misfolding of proteins will also damage the mitochondria--as well as other targets. Hence, an over-activated state will eventually lead to senescence, if no autophagic or apoptotic rescue operation steps in.
Clearly, autophagy and more importantly mitochondrial autophagy(mitophagy), rescues these cells, waiting in limbo. The untidy baggage is transported to lysosomes for degradation. This creates room and resources for new mitochondria to form to replace the old ones(turnover). Autophagy is not restricted to damaged tissue, when triggered by, say, diet restriction, the influence of glucagon or from exercise. It is regulated by PINK1 and Parkin protein.
Before autophagy salvage, there will have been some mitochondrial remodeling through fusion and fission and possibly cell death, and which is dependent on activity or some stress(metabolic or environmental like lactic acid buildup). Fusion allows the benefit from the healthy genes of one mitochondrion to compensate for the defect in a degenerate one. Some repair is possible. Eventually, with further stress, the situation becomes irremediable by this mechanism and cells become senescent. The defective mitochondria divide in the process of fission, if autophagy doesn't kick in, and this will lead to apoptosis. Alternatively, following some trigger, the brake is lifted off the genome with mutation to the p53 gene, and oncogenic drivers--growth factors(cytokines) and phosphorylation--will push the cell into a malignant cancer state.
A recent study found that a cell without mitochondria reverts to the juvenile stem state. Fewer but healthy mitochondria would mean low metabolism, less cellular stress and long life with the blessings of p53 or good immunity to pick the odd ones out(hence the long lifespan of the turtle). The study underscores the importance of autophagy in aging, disease, health and lifespan. Diet restriction, exercise, stress management, avoiding environmental toxins are measures to take to promote health. High metabolism followed by low, compromised metabolism and activity, resulting from unhealthy, defective mitochondria, will lead to inflammation, disease, obesity and aging, instead.
Dr. Oliver Verbe Birnso, MD.
Environmental toxins are hard to be avoided. It seems that they are everywhere in air and food. Agricultural chemicals should be applied in health and environment protecting ways.
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