Original Presentation is available:
Aging and senile degeneration of the body are inevitable processes that every person experiences. There are five main reasons for aging in the body, starting with
1) An increase in the stiffness of the extracellular matrix (ECM) due to the destruction of elastin fibers and the cross-linking of collagen fibers. This results in hypertension, a reduction in lung capacity, a loss of elasticity in muscles and skin, and chronic hypoxia of tissues.
2) Secondly, an increase in the number of senescent or zombie cells is observed, which produce pro-inflammatory signaling molecules and contribute to chronic tissue inflammation, multiplication, and eventually cell death.
3) Thirdly, mitochondrial dysfunction is observed, resulting in less functional mitochondria and increased production of reactive oxygen species.
4) Fourthly, the accumulation of various junk and debris, such as lipofuscin and amyloid, causes lysosomal dysfunction, leading to the accumulation of cellular waste.
5) Lastly, degeneration of the immune system results in chronic inflammation, and a rise in zombie cells form a vicious cycle.
Aging is accompanied by the stiffening of blood vessels and a reduction in the oxygen delivered to all organs and tissues, which leads to the development of chronic hypoxia. Therefore, energy metabolism in cells is shifting from oxidative phosphorylation in the mitochondria to aerobic glycolysis in the cytoplasm. This reduces the efficiency and total energy generation in the form of ATP molecules in many tissues such as the liver, skeletal muscle, and brain. Energy-dependent physical activity and other cellular functions decrease due to unmatched energy demand and supply. In return, a decrease in physical activity in older age accelerates this metabolic shift, forming a vicious cycle.
The accumulation of various junk and debris both in the ECM and inside long-living cells of the body is a hallmark of aging. Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion in long-living cells. Lipofuscin appears to be the product of the oxidation of unsaturated fatty acids and proteins. Aside from a large lipid content, lipofuscin is known to contain sugars and metals. Accumulation of lipofuscin happens because lysosomes don’t have the proper enzymes to break lipofuscin down into nutrients. In time, the lysosomes of long-living cells and macrophages get bloated from lipofuscin, become unable to work properly, and even die out.
The term “extracellular junk” refers to substances that serve no purpose, not even a biophysical one. The majority of this junk is classified as “amyloid” of one kind or another. Oxalosis is the accumulation of calcium oxalate crystals in the ECM. When oxalates enter cells, they damage the mitochondria, increasing the production of ROS while decreasing the production of energy molecules (ATP). Calcium oxalate accumulates in all tissues of the body over time, including the brain and nerves. It significantly reduces elders’ quality of life and self-esteem. Heartburn, muscle pain, spontaneous urination and defecation are common in the elderly, not to mention kidney stones, gout, migraine, dementia, and other conditions.
The number of mitochondria increases in zombie cells, to provide energy for the production of signaling proteins (SASP). However, these mitochondria are less functional than those found in healthy cells. They have a lower fatty acid oxidation efficiency. Instead, glucose is the primary source of energy in hyperactive zombie cells. An increased rate of glycolysis even in the presence of oxygen (the Warburg effect) is one of the hallmarks of hyperactive zombie and cancer cells, as well as cells infected by viruses.
There are several other hallmarks of aging, including epigenetic changes, damage to DNA, and shortening of DNA telomeres. However, I am skeptical about these factors’ contribution to aging, as we live much longer than individual cells. Organ-like cell colonies make up the human body, and old human cells may be revived by the Yamanaka factors and become pluripotent stem cells.
In conclusion, the aging of the body is a complex process involving various factors. However, by understanding these factors, researchers may be able to develop interventions that can help mitigate the negative effects of aging on the body.