Insane Medicine – mitochondria and aging – NAD+ and Sirtuins as part of the missing link

Insane Medicine -Aging and mitochondria
Insane Medicine -Aging and mitochondria – aging as a result of mitochondrial and nuclear gene miscommunication. Low levels of NAD in the cell cause HIF -1 to increase, which results in the nucleus and mitochondria to not communicate.
  • The mitochondrion is a cellular organelle that provides the cell with the energy needed to sustain life. It has it’s own genetic material that produces, in part with the nucleus, an oxidative-phosphorylation complex in the cell that produces all our energy. Basically, the mitochondria is a piece of machinery that acts like a battery for the cell.
  • As we age, it has been found that the genes in the mitochondrion mutate and function poorly. This may be the root cause of aging. NAD+ is a molecule used as an energy carrier that regulates the mitochondria, as it decreases in low oxygen states and results in a disruption of the oxidative phosphorylation complex. Increasing the NAD+ levels reverses this rocess.
  • In a functioning normal cell, the nucleus and the mitochondiron communicate with each other and manufacture, using their genes, the oxidative phosphorylation complex, which is the producer of the energy inside the mitochondria. It is the failure of the genes inside the mitochondria that result in the aging process.
  • A gene, called sirtuin 1 is involved in maintaining a clear line of communication between the nucleus and the mitochondrion. HIF-1 is a protein that the cell produces in cancer states and low oxygen states that interferes with this communication process, causing cell aging and death.
  • Aging muscles have been found to have decreased levels of mitochondrial genes.
  • Nuclear levels of NAD+ maintain the mitochondiral homeostasis, with decreased levels disrupting the oxidative-phosphorylation machinery in the cell and thus result in cell aging and death. Raising this NAD+ nuclear level in mice reverses this aging process. Molecules have been developed that can do this.
  • There is a separate system, the PGC-1α/β system, that also regulates energy metabolism in cells and acts as a transcriptional coactivator to regulate gene activity and function. It works separately from the above. PGC-1α regulates mitochondrial biogenesis and interaxcts with nuclear PPAR-gamma, which results in the interaction of numerous transcription proteins that affect cell function. This directly links the external stimuli of the world to the internal cell functioning of mitochondria. For example, PGC-1α may be involved in cholesterol regulation, obesity, and blood pressure.  PGC-1α may  integrate a number of internal cell signals with external signals. For example, endurance exercise increases PGC-1α levels and allows for lactate to be used more efficiently. SIRT-1 may bind and activate PGC-1α.. PGC-1α activates Akt levels in muscle, which is pro-survival in function. Massage therapy can increase PGC-1α, allowing formation of new mitochondria.
Insane medicine - mitochondria
Mitochondria are the work horse of the cell,producing it’s energy, but also they may be the root cause of aging.
Insane Medicine - Mitochondria are the work horse of the cell,producing it's energy, but also they may be the root cause of aging.
Mitochondria are the work horse of the cell,producing it’s energy, but also they may be the root cause of aging.  <- anti-aging and mechanism regarding this

  • Possible interventions for the process of aging?  Nothing is yet on the market, but some agents may have helpful anti-aging effects: trans-resveratrol is one option.  Red wine, mulberries, grapes, and peanuts have resveratrol. A glass of wine has a milligram of the substance. A higher amount is needed to be effective. About 360 mg may be needed to have an anti-aging effect. It has been noted that in countries where red wine is imbibed, people are thinner and live longer. An option for resveratrol in needed doses can be obtained here:

Calorie restriction has been a way to extend lifespan in animals such as rats. The process of calorie restriction causes the aging machinery to slow down.  Trans-resveratrol simulates calorie restriction without actually eating less. This may be a way to trick the body into a “fasting, yet anti-aging” state.



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